i hope everyone had a great opportunity to connect and hopefully get to speak to a couple of other attendees during lunch but today we are going to go ahead and kick it off with our introduction to the third session which i am very much looking forward to so without further ado i'm going to give you a quick introduction of dr paul hart he is an emergency medicine and hyperbaric medicine clinician who is the clinical professor of medicine in emergency medicine at the lsu school of medicine in new orleans he has initiated a private practice and has resulted in the largest case experience in neurological hyperbaric medicine in the world in this practice he's adapted the concepts of conventional hyperbaric oxygen therapy to wounds in the central nervous system that have spawned the subsequent academic and research practice he even worked on the first known case of global regrowth of brain tissue in humans and has now treated the largest series of drowned children in the world with over a hundred individuals as a part of that group this human work was again just an extension of his work in brain injuries and in in conclusion to that he also has a lot of literary work as well so he has a unique perspective on hyperbaric oxygen therapy published in his book the oxygen revolution and actually his most recent phenomenon was that in march 2020 so just last year he actually was the proposer of the application of hbot to coven 19 pneumonia based on the successful use of hyperbaric treatment so i am thrilled to see what he has to share today so i'm going to go ahead and hand it over to dr harge [Applause] all right well thank you very much and uh a pleasure to be here again and tim where are you i i was crushed to hear that uh luke had died i had no idea what a terrible tragedy and i just wanted to remark at the beginning here we didn't know about that um anyways i'm very thankful to be here again this is such a wonderful opportunity to reach all the families and and talk about hyperbaric oxygen and what i'm going to talk about today among other things is stem cells in conjunction with hyperbaric oxygen but before we do that everybody needs to understand what hyperbaric oxygen is so i'm going to try to characterize hyperbaric oxygen look at it as a treatment for wounding essentially in any location in the body and of any duration and then ask some very important questions why does it work for so many diseases does my child have a brain injury well what happens if my child doesn't have a brain injury and then of course when's the best time to start hyperbaric oxygen and then lastly we're going to go through a number of things about stem cells which actually when i sat down and started pulling the literature i was even surprised at what i found so what's hyperbaric oxygen simple question right it's been unanswered for 347 years until 2008. and this has been the root of the problem in this specialty no one has understood it and uh we think we finally do so if we kind of look at a physiologic definition it's a treatment that uses increased pressure and increased oxygen to treat diseases functionally what we're doing we're exploiting all living organisms sensitivity to pressure and oxygen and everybody of course understands oxygen we all are sensitive to it without it we'd be dead but how about pressure nobody ever thinks about that yet we live in a pressurized environment here and so it turns out what is pressured pressures the weight of air from the elevation at wherever you're standing up to 60 miles in the atmosphere where essentially there is it's very thin there's no air beyond that and the weight of that air 60 miles up where we are standing right now is 14.7 pounds per square inch that's one atmosphere of pressure at sea level and then of course there's hydrostatic pressure so when you go below sea level underwater you now have increased pressure and every 33 feet of seawater is equivalent to those 60 miles of air pressure so a column of water above you 33 feet is another atmosphere well here's a complicated graph and don't waste a lot of time on this thing but here's the hyperbaric range of pressure so here is outer space zero pressure essentially all the way to deep sea diving and of course the other way to look at this that dark line there is sea level so ten thousand twenty thirty forty fifty sixty thousand feet of altitude and this is the safe zone where people can exist but you see what happens here we are at twenty percent oxygen roughly and here is sea level we're safe here breathing air but as we start going to higher elevations you need more and more pure oxygen to exist well it turns out hyperbaric oxygen is just operating in this range here and really mostly that range right there so it's a very small range of the entire pressure spectrum well it turns out all living organisms are adapted to the pressure they live at so if you look at altitude we have all sorts of different species of birds that live at different altitudes and this is just everest uh to to show you the different altitudes but it's true also of livestock of plants crops they have a an ideal pressure range where they exist fortunately most of them do very well at sea level which is where most of us exist as well but it's true also below the surface so it increased pressure there are different species of plants at different levels in the ocean and there are different species of animals so i don't know if anybody has seen the exploration of the titanic when they went down with that uh i forget his name james uh whatever i went down there with that little uh you know robotic submarine and saw the sea life down there at 10 000 feet it's like creatures that don't exist anyplace else but they're specifically exam adapted to that very very very high pressure environment okay so here's atmospheric pressure here we are at the surface and that's the 60 mile limit or 100 kilometers here's where the satellites are and you can see the airflow et cetera but the weight of that column of air is one atmosphere of pressure and of course below sea level same thing so wherever you are below sea level it's the weight of water above you that is that pressure and i'm going to show you just one equation and this is very important because every chemical reaction in the universe and on earth and every living organism those chemical reactions either liberate energy or they consume it but there's a change in energy to it and the important part for all of us is whoops not the clicker it's that right there pressure is a component of every chemical reaction so when you change pressure you are potentially changing every chemical reaction that's going on in our bodies so when we deliver a hyperbaric treatment you shut that chamber door and turn the pressure on you start changing your body and in particular any wounded area in the body is subjected to that and there's the universal gas law that governs that it is inescapable everyone in this room every living organism shut the door put it turn up the pressure it is now affecting your biology well what else are we affecting when we turn on the pressure or turn up the pressure it turns out we are affecting our genes now when i went to medical school many years ago we were taught that our genes you only needed them when you reproduced your sex cells right you pass on all your traits to your offspring no every cell in our body its vitality is dependent on those 46 chromosomes the genes along those chromosomes continually being red and unread like a ticker tape the genes code for proteins those proteins run all those chemical reactions in our body so our genes are actively working as it turns out hyperbaric oxygen is unique in all of medicine in that first of all to get the effect you have to fully enclose the body in a chamber and uh we're then affecting gene expression which i'm going to show you in a minute so let's go back to our physiologic definition and what we're doing it's a treatment that uses increased pressure and increased oxygen to treat diseases well what kind of diseases turns out they're mostly wounding conditions the vast majority of them so hyperbaric oxygen is a treatment for wounds in any location and of any duration and how do we heal wounds with hyperbaric oxygen you have to grow new tissue how do you grow new tissue you have to stimulate the cell to divide how do you do that you have to go to the nucleus of the cell which is where cell division takes place so somehow hyperbaric oxygen has to stimulate the nucleus so if the daily input is getting in a hyperbaric chamber turning up the pressure on the oxygen and the output is growth of new tissue you have to go through the nucleus and it turns out what we're doing this is one of the oldest gene therapies known to man this is a gene signaling drug and this finally came to understanding i'm going to show you in just a minute but let's just look at our chromosomes so everybody's familiar with the double strand helix of dna well dna it turns out has these little purple histone protein balls that are wrapped i should say the dna strand is wrapped around these little balls and then those are wrapped in a greater coil which is our chromosome so if we look at one of the smaller coils here with the histones here's the dna and there are the histones in the middle of it these different colored proteins they sit on the jeans and they have these little arms that stick out and it turns out those little arms are sensitive to everything the environment food additives chemicals pesticides uh air pollutants every substance alcohol tobacco drugs you name it you chemically can change these things and when you do you change the conformation and shape of the protein it's electrical charge and it lifts off the gene or it locks it down but when it lifts off the gene gets read like a ticker tape the protein or enzyme is made and away you go well it turns out you can permanently affect these histone proteins and what is new to medicine is that if you do that to your ovaries and you know your eggs or your sperm you can pass these traits on to your children just like changing the dna code these are called epigenetic changes it turns out where is hyperbaric acting it's acting epigenetically somehow we don't even understand it it is affecting these proteins and allowing the genes to be read which goes to the understanding of this therapy for 347 years nobody has understood it until 2008 dr godman up in massachusetts took human cells and what they had done is take skin biopsies from done in the hospital people biopsy a mole ground it up and they isolated the cells that line the tiniest blood vessels in our body and they're called endothelial cells they are the most reactive it's where all of the things that occur in our body occur at the tissue level is with these endothelial cells affecting blood supply and cells and nutrients and things going across there and what they did is put them in a petri dish and stuck them in a hyperbaric chain began one treatment and did a mass continuous gina ray analysis for 24 hours and what did they find at the end of 24 hours over 40 percent some 8101 of our 19 000 protein goating genes in our dna were turned on or turned off 40 percent of our genome affected by a single hyperbaric treatment and the largest clusters of genes turned on are the growth and repair hormone genes and the anti-inflammatory genes largest clusters turned off genes that cause inflammation and the ones that code for programmed cell death so every time you get in a chamber the wounded areas in your body you're stimulating tissue growth inhibiting inflammation and turning off cell death which leads to what are we using it for well this is the united states list of reimbursed indications and on the right-hand side i wrote they're all wound indications acute chronic sub-acute but you know that's air in artery carbon monoxide a crush injury like from trauma diver's disease problems with diabetic foot wounds massive blood loss radiation damage tissue flaps and grafts that aren't healing burns stroke of the eye causing sudden blindness sudden hearing loss and then these five things are infectious diagnoses the most common one you've probably heard is the flesh eating bacteria they are wounding infection diagnosis not like the simple skin infection take some antibiotics go away no harm no foul no these cause wounds but go to russia they treat 70 diseases 49 in china 30 some in japan an article critical of hyperbaric medicine 1987 identified 132 diseases hyperbaric oxygen been applied to vast majority of them are wounding and inflammatory conditions i've treated probably a hundred now almost 90 of them are neurological diagnoses luck out for the 132 i'm catching up with you well how's it work for so many wounds it doesn't necessarily work by treating the disease it treats the underlying disease processes that those genes have impact on so essentially these processes are common to many many human diseases our body only has certain ways of reacting to an insult whether it's an infection a trauma whatever and those underlying disease processes that are common to so many diseases is what hyperbaric oxygen targets so the biggest question we have to ask really you parents and because we're talking about pediatrics here does my child have a wound in his or her brain and the answer to that is often not appreciated or parent or it's deliberately concealed i'm going to give you some examples i got called by mother had a five and a half year old boy who had global developmental delays and autistic behaviors and he was just he had so many problems and we get to talk to her and he was born three weeks late she had gestational diabetes nobody was checking her and she delivered a nearly 11 pound little boy a watermelon 36 hours of labor and a child's head was born grossly distorted big hematoma blood clot under his skin between his scalp and his skull and from day one had neurological abnormalities they're in a small town the neurologist gave him a diagnosis that didn't fit because he didn't want to lay the blame on the birth process and get the obstetrician in trouble i said you need to go to a different center go someplace distant get an independent opinion she did she went to an academic medical center and they gave another diagnosis that didn't fit it turns out that neurologist had trained the neurologist in her hometown i said go 500 miles and ask the neurologist do you know these other two guys because you need an independent opinion had no connection to him went in there he reviewed the record spent a half an hour and he said look your child has a birth injury it's very very obvious mom didn't know that changed the whole scope now of what what we were going to do with the child another child of mine a year and a half old neurological developmental delays global developmental delays and nobody has any idea what's wrong with this child and mom asked me if i treat any child children like they said they do yes we have we don't know what's wrong with them but they're developmentally delayed we've treated them they seem to respond so the day of the appointment she goes by the hospital to pick up medical records for her the mom mom had a doctor's appointment and she goes to the clinic and the clerk said uh would you like to get your daughter's medical records too and she says i was just here two weeks ago i got him she goes well you know sometimes you know things come into the medical record what is this well okay yeah whatever she brings back the child she goes oh look there's a new folder in here copies it gives it to mom sticks in an envelope and mom didn't have time gets on the highway comes down and comes out says well i got some new medical records this may help i said what's it say she goes i don't know open it up baby was born with a glucose level in the 20s wasn't discovered for 16 hours didn't get treated for another eight hours this was a child with a hypoglycemic injured brain concealed where was that it was an illegal file statutory limitations now had run out got back put in the medical record now and i told her you take this to the neurologist and let them see it so it will change their opinion about what's going on with them most recent example a little autistic boy but this is an autistic boy who from day one has had motor delays and problems and coordination balance and you know neurological abnormalities and autism no that's of social reciprocity and speech and repetitive behaviors and all that he didn't have that uh he had a subsequent deterioration they gave him some of those but the whole point was i have the parents send me medical records birth records and we get on the phone and they also send me a self-written history so i get the birth records in the hospital nothing wrong everything is a-okay turns out it was a premature stimulated labor the obstetrician told her to take castor oil because he was going off vacation they wanted to get the baby delivered early so she went into premature early labor challenge delivered two and a half weeks early and but there's no record in the chart of anything wrong but take a look at this mom writes to me my son was born at 37 weeks weighed 2.6 kilograms meconium was present at birth ho-hum no family history of autism wait a minute the child pooped at birth in the birth canal why does a child poop during birth it's called fetal distress the brain is compressed not getting enough oxygen the child is in distress and they poop meconium staining it's a sign of damage and injury at the time of birth here's the answer to what is wrong with this child she subsequently now went back and got medical records and what did they find pathological analysis of the placenta showed she had an infection that wasn't picked up wasn't treated and of course nobody told her it's in the medical records the pathology report and here is just another problem sarah scan spec brain imaging company in denver colorado they took 3 600 of the people who came to them for brain problems to get a spec scan and they got their medical records from birth all the way up to the time of the imaging and they hired some coders and you know data extractors and they had a massive excel spreadsheet 18 1800 columns and they input all the data age sex you know the amount of gestation time labor time everything all the way up through their life doctor visits all the medicines everything what did they find 60 of these people had a birth incident that they implicated in their neurological problem and finally i'm just gonna mention the cowan study in 2001 300 babies two groups all of them born at 40 weeks the one group picks your perfect birth everything's fine all good and the first three days of life has a grand mal seizure out of the blue what happened nobody knows compared to term babies who were born same thing normal pregnancy and everything but profound injury at delivery uterus ruptured placenta ruptured placental bleeding something child born in a rest etc but unequivocal neurological injury they do mris on all of them in the first two weeks of life what do they find in the profound neurological injury once 78 of them have acute brain injury on mri none of them have any injury due to the nine months of pregnancy the other picture perfect births with the single grand mal seizure 68 had evidence of acute brain injury from birth none of them had any evidence of a gestational problem the point is we take it for granted but the trip down the birth canal is one of the most perilous in life for many people and there's a lot of injury that's imparted and personally i believe that that leads to a lot of the diversity the wide range of normal that your pediatrician often tells them oh don't worry he'll grow out of it that's normal no it may not be look to the birth history so why is it concealed well you know liability is the big problem so what if you don't have an acquired injury or one that you can identify well i often have this problem they call it say oh no there's no problem but oh my child has add add is not normal development it's become so common now but it's very likely from all these environmental insults and other things and frequently it can be traced to a known injury in the developmental process to a child but usually that's a sign of an underlying problem in pathology well how about genetic syndromes when people call me up about those and when i started this i said look i can the one category of diagnosis we can have nothing to impact with you know hyperbaric oscillator had no impact on would be genetic diseases that's before we knew about epigenetic effects and so in 1995 we had the first premature aging syndrome 19 year old girl steroid lipofuscinosis of the brain it's a fatty acid problem that's in all membranes of our cells and it fails the patients all die by 25 years of age and with brain imaging with videos with exam we treated this girl and lo and behold she improved now i've treated over 30 genetic disorders and i can tell you 98 of them have responded and we believe it's because of this epigenetic influence affecting other genes that may overlap and help the genetic syndrome but it works surprisingly okay so when's the best time to start hyperbaric oxygen right at the time of injury and i'm going to talk about this with the drowning problem is we can never do that in the hospital it's almost impossible you know once there's a wound there's a timeline there's an evolution and the pathology changes with that wound as time goes on it turns out hyperbaric oxygen wherever you intervene can help truncate that and it stimulates now the repair process but getting that in the hospital is very very difficult and if you look this is the story of all the drowned children that i've treated which is now over a hundred first 40 of them were up to the time of little eden carlson in 2016. they were all at least a year after drowning and we saw improvement in them but it just wasn't anything like we're seeing now with the children who are four weeks to six months out but where did the best result come in all of those this little guy christopher dixon 90 minutes after he was pulled out of 15 minutes submersion in the pool in the er intubated you know paralyzed now sedated and everything because he was thrashing around and on the ventilator we got him in the chamber 90 minutes after they pulled him out of the pool single treatment next day took the sedatives paralytics off he woke up extubated him went home in three days that was july 8th 1997 went back to school when school opened in august there was a magazine article written about i've written a book chapter for 21 years summarizing this the evidence for treatment immediately is strong in his type of injury global ischemia so and there's a little eden carlson so now we've got over 100 children and mr will boyton through his work at texas children's with the doctors now we're raising money we're almost there to hire the researchers to go back and review all of these charts and compare them to a control group so that we can get something published to try to leverage the doctors with and we're hard at it but what's the general finding first of all global ischemia anoxia which is what dr crawford was talking about is the most difficult of all the neurological diagnoses to treat uh it doesn't just selectively injure one area it's the whole brain some areas more than others um and if we look at this typically there's been no treatment for it and i say prior to hyperbarics i say prior to hyperbarics as well as all these other therapies that dr crawford is doing prior to stem cells now etc but we used to have nothing when i started doing this and if i look at all of our children over the years these hundred children i would tell you 85 to 90 percent of them respond there's about 10 percent that don't and these are the ones who are sent home on hospice who are so severe rigid locked in immobile uh uh just extremely damaged and now there may be some things that can be done and maybe it was more hyperbarics if we did it in combination with other things but i would just tell you it's not perfect but if we look at these 85 percent the children with cortical vision impairment and autonomic dysfunction a hundred percent of them will get some relief and there is a published series of six adults out of china severe traumatic brain injury who 45 days after the trauma were still in nearly non-stop autonomic storming they gave them an average of five treatments actually it was reversed after three hyperbaric treatments and the storming stopped so there's precedent for it and it's been our experience as well if we look though at the other functions that are affected i tell parents there are eight other things and on average we see improvement in five of these i just can't pick which ones and the degree of it but effect on alertness and awareness gross motor function fine motor which is hands tone balance sitting or standing depending on stage of development oral motor which is lip tongue fairing swallowing secretion handling speech and cognition and lastly temperament you know many of these children are very irritable and it has a calming effect on them so again when is the best time it's in the hospital but we can't do that so what can you do instead hyperbaric oxygen remember is two components increased oxygen increased pressure you can still use the increased oxygen but you can't use it how it's been traditionally used if i plop over right now and hopefully somebody does cpr on me what's going to happen ems gets called they're going to stick me on 100 oxygen it used to be go to the er and you stay on 100 oxygen for 24 hours you will not get the same effects that you do if you give it and take it away because you're using it for signaling and there's precedence for this in acute severe traumatic brain injury and acute stroke we used for years in wound patients in the hospital who ran out of time reimbursement time or hospital time for hyperbarics we sent them home on an oxygen concentrator intermittently a couple times a day having them breathe oxygen for an hour or so and what i've done this with patients neurologically and so that's what happened with eden carlson if you read the story she was too unstable to travel from fayetteville arkansas to new orleans there's nine hours of nothing between that i mean a lot of woods in a few cities but you don't want to get caught out in the middle of nowhere with a child who can't breathe pulling into a podunk er and hoping somebody can intubate her you know so i told her look we need to strengthen her so if you look at the video in that article i had mom video her right before the very first nasal cannula oxygen and afterward and it is a phenomenal change you'll see we now have done this with somewhere between 60 and 80 children in icu's all over the country now and a few internationally and they respond generally within 24 to 48 hours you see it first in their eyes and facial expression but it's used as a signaling device well what are the barriers to doing this the first is the mentality in neurology neurology is a diagnostic specialty has been for years and when i was in medical school we were taught there is nothing you can do for a neurologically injured patient it is time natural history letting nature take its course etc it is the only organ in our body that the medical profession has taken the attitude you can't do anything for think about that pediatricians surgeons of all stripes cardiologists kidney doctors every specialty has not said nothing we can do cross your arms but that's been kind of the the mentality and thankfully it's changing but it's been it's taken a long time we've also got medical paternalism where the doctor is going to make the best decision for you and your child your child will have a quality of life we're saving you a life of heartache only to prolong the inevitable result which is death or that is from one of my mothers she's bilingual and i think she translated that the doctor told her the child was going to be a vegetable so that's what she said your child is going to be a plant this was two months ago and of course what else there's a rush to organ harvest this is frankly cruel and criminal uh because parents are taken advantage of and it's part of that paternalism and i i have encouraged the parents it's it's not going to be believed by me but you parents need to band together and write about this because there's this rush to organ harvest when there is hope and treatment and it's just that the problem is the doctors might not know and so first thing is we end up having to get past the ego you know it's not being done they're the experts in that icu care in neurology and the implication is wait if we knew that it worked we'd be doing it but it doesn't work and that's why we're not doing it well no they don't even know about it is the problem and and that comes to this and and it's just confrontational immediately i mean i end up getting on the phone with them to try to explain even the normal barricades and they've never seen the literature on it but about seven years ago we did a survey of all american medical schools and and went to their academic department their curriculum what they're teaching medical students and asked them how much do you teach about hyper american medicine 75 percent of american medical schools teach zero about pressure biology hyperbaric medicine another 25 it's a fraction or maybe one lecture so there's a problem out there that they're not informed the bigger problem is the attitude you have to be open-minded and admit you might not know something and defer to somebody else you know go ahead i'll feel the question ask me about pork bellies and pork belly futures i'm sorry i don't know anything about that well in medicine go to a medical library it is filled with a jillion volumes none of us know all of that stuff and when you don't you have to say i don't know i give you an opinion but i can't give you an informed opinion and you're trusting us to give you reliable information and that's where the problem is here well it turns out the decision-making in severe acute pediatric neurological injury is exceedingly personal you know there are religious implications there are instinctual things here that you know to preserve life uh it's complicated by uncertainty you don't know what the outcome's gonna be you can't even discern how much neurological activity and brain activity is in your child when they're on a ventilator like that and sedated uh or not sedated uh and and many parents they can sense that their child senses them they'll say when i walk in the room we see him stir we see his pulse go up etcetera and then it's just reflex no i could tell the experiment's been done on near comatose people showing the amount of neurological activity in there we have no idea they're in there the reality is though we're now achieving results we had never seen before and with the combination of therapies it's a whole new world we don't even know what the upper limit is and how are we doing that because at least with hyperbaric oxygen what i know is we are treating the underlying disease processes and along with those gene effects what we're doing is influencing stem cells and so that's the last part of this and i'm kind of have to hurry so you know what are stem cells dr profrock is going to give you a whole lot of information on this i'm not expert in it so i'm just going to try to focus on the stuff related to hyperbaric oxygen but they're undifferentiated cells there are premature cells that are formed from you know the very beginning sperm and a going together and and then the stem cells themselves can develop along the way and i'll show you a little graph about that but you know the analogy those stem cells can then develop into any cell in the body any type of organ any tissue and it's kind of like a child child is a stem cell they can grow up to be a mom a caregiver a dentist a lawyer maybe that's a d different no i'm just kidding uh a banker no i'm not one of those doctor hating or a lawyer hating doctors i am not but it's always fun to joke about it um and uh so uh differentiation well here's a the different types of stem cells and this is the one we're most commonly seeing in is most commonly used in the medical profession and mesenchymal stem cells they can come from a variety of different areas you know our bone bone marrow really any tissue adipose tissue umbilical cord whoaton's jelly and of course our peripheral blood and they can differentiate into all sorts of other cells so what does hyperbaric oxygen have to do with stem cells well it turns out quite a bit but it also turns out that stem cells are in every tissue and organ in our body and the most important sites are our bone marrow adipose tissue which dro fox is going to talk about and the brain so here is one of our long bones that's our femur that would be the hip socket and the ball that goes in it and here's right down by the knee and two main types there are others in the bone marrow but the big ones are the hematopoietic ones that differentiate to all of our blood cells and the mesenchymal ones that differentiate to all of our different tissue organ cells of course you can go in and harvest them you can go in your hip you go in the long bones and take them out and process them you can also stimulate them with granulocyte colony stimulating factor which is a type of hormone and it'll cause release of them from the bone marrow or you can do some other things with it uh which i'm going to show here but um stem cells are also produced in the brain and there are two primary areas that they're produced so this is a slice of the brain going straight through my eyes to the back of the head like a stack of pancakes and you see the eyes here deep in the center of the brain these two you can see that kind of looks like a little sea horse like that's the hippocampus so that's right at the medial aspect this is the temporal lobe here on each side so it's right deep down in the center of the brain if we look at the side of the brain and our ear would be right there here's our temporal lobe makes sense it's right under our ear that's where sound processing is and the tempora the hippocampus runs along like that that purple structure and right along the middle aspect here the hippocampus that area is associated with short-term memory well on the very inside edge of it is that green strip there it's called the dentate gyrus of the hippocampus that's where our stem cells are made in the brain well it turns out they're also made in one other area and so this now is a different slice we're going from the top of the head straight down through my chin so a slice like this and you're looking straight on at the person so right ears out there left ear is there here are the two temporal lobes and the hippocampus is right down there and the dente gyrus is going to be on the inside there this is that deep gray man as dr brad crawford showed you uh the basal ganglia thalamus but the basal gangly associated with motor but what's up here the fluid system in the brain the ventricles and what is right on the edge of the ventricles is the subventricular zone that's the other place our stem cells are made so the primary there's also they're made in the amygdala but the point is the major places are here and down there our stem cells are made okay well it turns out that stem cells can migrate from their birthing places in the brain to sites of injury that's the way the brain tries to heal itself but they also can home from the bone marrow and maybe other sites in the body to the brain and sites of injury but natural homing in the brain what happens if you've injured the subventricular zone and the dentate gyrus this is the coronal cross sections from top of the brain down through the chin we're looking straight at the person this little drowned child and if we look at the areas of the brain that are affected in drowning there it is the subventricular zone where stem cells are made and down here look at that dentate gyrus of the hippocampus and of course here's the basal ganglia all bright white and injured and even the whiteness of this cortex there's diffuse injury but the point is our areas for making new stem cells get preferentially injured in global ischemia and drowning so these kids have a real setback there and if we look at this more mris looking at both the gray matter areas and the white matter connecting tracks in the brain that are injured in drowning this is a big study on or a sizable study on children in the chronic phase so this is months to years afterwards you can see it's right in the center of the brain here where dr crawford tried to point that out to everybody well what's so peculiar about it it's that same slide that he showed it's those lentate arteries here and what happens is they come to a terminal end in this area which is part of the watershed zone that he mentioned watershed zone is where the three major arteries on each side of the brain come to confluence and it's where blood flow and blood pressure are the least and they're the most subjective and sensitive to injury when you drop systemic blood pressure so if one place has a pressure of 10 and the other place has a pressure of 80 and you drop the blood pressure to 60 where's the blood pressure lost first it's in that 10 area and that's why the watershed areas get damaged so easily well what are those areas control that's the deep motor area and the connecting tracks from the cortex the motor area as well as well as many other structures there well natural homing also occurs from the bone marrow so you got an injured brain your bone marrow is going to release stem cells and they'll go to your brain the brain is trying to send them from their birth place in the brain to your injured areas but this is a pretty slow process and it's painfully slow and it needs kick start and that's what all these therapies are that you're hearing about today is trying to stimulate brain recovery so what does hyperbaric oxygen does do it does a bunch of things it stimulates production and release of stem cells from the bone marrow differentiation of them meaning maturing into other cells stimulates proliferation whoops proliferation of them and differentiation at the sites of injury facilitates implantation of them and we're now finding it stimulates production of them so that you can harvest them and that's the most exciting thing and at the end and i'm going to try to i may be running out of time try to go a little faster here but all of this came to fruition with hyperbaric medicine 2006 where they were treating 26 patients for radiation injury to the head and neck and this one of the standard indications for hyperbaric oxygen had cancer take the cancer out irradiate them it damages the blood supply the teeth rot you now go to take teeth out and you don't have enough blood supply to heal the socket you get necrotic bone painful it's a terrible condition and problem but if you give hyperbaric oxygen before take the teeth out right afterwards no problem so what they did was they decide to measure bone marrow stem cells that are released into the circulation of these people just undergoing hyperbaric oxygen for wound healing and what they did is every day a two atmosphere oxygen treatment for two hours which is long and then they looked at the blood after the first 10th and the 20th hyperbaric treatment and here are the stem cells that were in the blood before the hyperbaric treatment everybody has a certain number in their blood but after one whoa big jump by 10 there were more circulating after the 10th even more by 20 even more and after the 20th even more and this is where they stopped measuring it just they designed the experiment they were going to go all the way to 30. but who knows how far you could go you keep stimulating them and here of course was evidence that the stem cells hyperbaric was causing them to differentiate and start their process in forming new tissue cells first step in that is they have to change the proteins on their surface so they can now attach to the blood vessels inside lining those endothelial cells we talked about to now take their trip out into the tissue where they start maturing and become like a new heart cell or whatever and what they showed is that that change in the surface protein didn't happen until 20 treatments so the maturation phase of it took a little long with the hyperbaric ocean but it still stimulated it they then looked at mice where they took a little gel plug and stuck it under the mouse's skin well that becomes an inflammatory site it turns out stem cells will home to that they then gave three groups of mice different amounts two hyperbaric treatments five daily treatments or ten and then they went and looked in the bone marrow well they had air control groups for each of those look at the stem cells stayed the same untouched same number but look what happened two hyperbaric treatments significant increase five hyperbaric treatments a whopping four-fold increase and by ten days they still have a big increase so you're stimulating production of them in the bone marrow and you're releasing them into the circulation and of course here they are in the bone marrow with their surface proteins they attach get out of the bone i should say they get out of the bone marrow into the blood vessels and then they attach it to the cells here and cross over and they now start forming new tissue so we can stimulate bone marrow stem cells to go into the circulation and home to sites of injury we can take them out we can re-inject them we can take them out and groan them and re-inject them it's all the same or we can harvest them from some place in the body and inject them and they home to sites of injury and once they're there they multiply and divide and they secrete a lot of hormones to stimulate tissue growth well as it turns out hyperbaric oxygen promotes stem cells in acute stroke and it promotes homing of them from the bone marrow to the site of injury in the stroke and this was a study done in rats where they induced a stroke in the rat and then immediately after they started hyperbaric treatment like we'd like to do in the hospital but can't did it once a day for two days five days or 15 days and what they found at the end of 15 days was stroke size decreased number of stem cells increased around the stroke new neurons increase around the stroke there was reduced inflammation around the stroke and the rats did better neurologically and they did it with just two hyperbaric treatments but they did a lot better with 15. and so if you now look at here are the bone marrow stem cells around the stroke and this is the group that they just went and did an operation but they didn't stroke them they closed them up this is the stroke rats so they ended up they make little stem cells in response to injury two hyperbaric treatments more stem cells and three weeks hyperbarics a whole lot of stem cells around the stroke and these are the new neurons same thing with hyperbarics a lot more neurons that are forming well look at the amount of inflammation in the stroked ones way down after just two hyperbaric treatments by 15 it's the same amount of the rats that just got a sham operation and no stroke so a big effect and of course here is the stroke so the sham ones no stroke there's the stroke that white area two hyperbaric treatments almost gone by 15 it was almost imperceptible well it turns out that if you just inject stem cells iv they will home and differentiate in the brain and this was another study in rats where they put an inflammatory focus right up here in the top of the brain and they then injected the bone marrow stem cells and they looked at what happened on day zero day one i'm sorry day nine uh day one and day zero and if you look at this the stem cells are the dark ones the stem cells all migrated to the area and took over and you see that here as well and here was the injury site with inflammation no stem cells stem cells are in red and now they start differentiating into new glial cells support cells again the hyperbarics is causing that stimulation this is one turns out hyperbaric oxygen stimulating this in traumatic brain injury and what they did was take the rats and they dropped a little weight on their head well this the rat that didn't get the weight drop he's got a normal looking brain there's the big area that was damaged by the weight drop and here it was after hyperbarics a substantial decrease in size and what they did was three hours afterwards again in the hospital when you want to give this hyperbaric treatment they gave a two atmosphere treatment once a day for seven days and then looked at this in the rats and what they found was increased number of stem cells around the trauma area and down in the hippocampus remember that's where we're forming new stem cells naturally in addition they had an increased number of neurons at the site up in the cortex as well and all this is showing is the new stem cells as they're growing in the hippocampus there and these are the new neurons that are also forming so you know all the same information but those are all acute conditions how about in a chronic condition you know by the time i've seen 95 percent of my patients it's an old injury and that's the majority of the patients we've seen over all of these years and that's what all of this was based on and these patients improve in the chronic state but do we have evidence in a chronic animal model yes we do and here was a rat study and when i saw that i just busted out laughing demented rat yeah what i mean was that a rat that can't find his water bottle it's uh the way they did this is they were trying to duplicate vascular dementia in humans vascular dementia is small blood vessel growth or multi strokes that have knocked out enough brain tissue that you're having trouble thinking now and so they went in and they tied off two of the arteries to the brain and what happens is the rats lose brain tissue 30 days later they did a avoidance response test and what they do is they they have a little two-room cage and they shine a light at the rat and if he doesn't go in the other cage they give him a little shock on his foot and enough times they do that pretty soon he assumes you know he associates the light with the shock and he skedaddles into the other room and it's an avoidance test that they do so 30 days later they do the avoidance test and then they gave him a hyperbaric treatment once a day for 10 days versus controls and sham operated ones and then they repeated all this but they also looked at blood flow in the brain they stained them for stem cells and neurons up in the area of the brain associated with intelligence in the rat which is our parietal cortex right above our ear here you can put your hand on that's your parietal cortex and what they found is this hyperbaric oxygen improved learning and memory and brain blood flow it improved stem cells and new neurons up in the cortex and essentially it also did the same in the hippocampus which is where we're normally forming our stem cells so essentially in a chronic brain injury model hyperbaric oxygen reversed memory and learning loss improved blood flow neural stem cells and neurons in the cortex and there's a little thing shine a light if he doesn't skedaddle over there they shock them and it just shows they're pretty good at getting into the other room there is after they're demented and after hyperbarics they do better and here is their blood flow when they're demented it's down after hyperbarics it's up and this is just the figures on the stem cells i'm not going to go through it it's a little bit busy but the whole point is new stem cells new neurons growing new brain tissue well where have we seen this before this is the veterans study i did with hyperbaric oxygen and what we found after 40 hyperbaric treatments 88 significant areas in the brain of increased blood flow and they're in the white manner which are the connecting tracks which is where traumatic brain injury damage is located and on the surface of the brain in the cortex we also saw it but what did we also see if we look at the bottom row here is the hippocampus that area remember those were green on that other slide i showed you what we found was significant increase in blood flow to the hippocampus and simultaneously improvements in iq 15 points delayed memory working memory and an executive function all significantly improved just like the rats in fact when i first showed this stuff in humans with the cases the comment from the doctors in the audience well that would be believable if you had an animal model so we when we did the animal model and that's exactly what we found and to this day it is the only improvement of chronic brain injury in animals in the history of science and the joke was it was the human protocol we'd been doing all those years so the net result of all those stem cells is the happiest little guy on earth this little jersey michelactic uh what a bright light poor little guy preemie quad cp and uh after we had treated him and i think he's also been here and seen dr crawford he's had a very noticeable improvement okay well do we have evidence for this in humans i think i got to hurry we do and going back to 2006 they took diabetic patients and they harvested their stem cells from their bone marrow and injected them into the main artery to the pancreas so the pancreas sits right in the middle of our abdomen here behind the stomach they injected them in there but they gave them five hyperbaric treatments before and five after a year later they measured all of this function and they found fasting glucose had dropped by 50 percent from 205 down to 105. hemoglobin a1c which is the binding of glucose to our hemoglobin molecule had gone down from 8.8 to 6.2 all of these are significant if you look at this it wasn't just some of them that did this look at the error bars on this all of them were in a very tight narrow range they got the same effect and here was the amount of insulin they were taking 35 units of insulin a day and they ended up with two and a half insulin units of insulin here was another evidence is what it the implication was the hyperbaric oxygen maybe facilitated implantation of the stem cells well then there was this little case from india 16 year old boy his three older brothers and sisters had all died of this genetic d4 defect carnitine transporter deficiency carnitine is an ammonium compound that transports fatty acids into the cell where your mitochondria then burns it for fuel and of course if you can't do that in the heart you got a heart that fails and that's what was happening everybody dies with this and so here he was in heart failure and this is just to show you what ejection fraction looks like so a normal person the heart squeezes squeezes blood out about 70 percent of it gets squeezed out when the heart starts failing it's less you're 60 and when you're really in failure and down to ejection fraction 20 it's just squeezing a little and you got a lot of blood left in there well by the time he was 16 years old well here he was at seven years of age before it was really manifest he was up in the 60 range but for the timing of 16 it was down to 30 and after the first stem cell what they had done was inject stent cells but they did 20 hyperbaric treatments before and 20 after and what they found was he got out of the hospital and it already jumped up five percent five months later it had gone up to 55 by the following january they gave them another dose of stem cells and hyperbaric oxygen it was still a 55 but a year later look at this 84 i mean it's like super normal now it subsequently drifted down a little bit they had to treat him again but the point was hyperbaric oxygen may have helped or been implicated in the implantation of these stem cells well here is a group of doctors also that did the same thing in humans let me show you with their experiment but they started first with mice and they took mice they irradiated them so that they were they wiped out their bone marrow but before they irradiated them they did a little test to stain for illuminate stem cells near bone marrow you can see in both groups the control group no hyperbaric hyperbarics before they got irradiated they all had bone marrow stem cells all good then they irradiated them and they injected back the stem cells and then went and measured and in the ones that didn't get hyperbaric oxygen where they had just done a single hyperbaric treatment and then inject the stem cells those rats showed no uptake but the hyperbaric rats look at that the stem cells implanted in the bone marrow the only difference was one hyperbaric treatment they then went on to do this in cancer patients where they chemically wiped out their bone marrow and did the same thing single hyperbaric treatment then re-infused blood stem cells and what did they find by follow-up 100 days later or so and on blood draw they'd had a significant reduction in the time to repopulate their bone marrow white blood cells platelets and there's this inflammatory thing that occurs with chemotherapy you may have heard about it it's mucositis where people slough the inside of their mouth it's painful it's horrible you can't eat can't swallow it turns out 64 of the control group had it 26 in the hyperbaric oxygen so it appeared the hyperbarics was facilitating the implantation the last case that showed this is my most famous patient a middle-aged man a very famous man very wealthy and his job involves giving talks like i do uh here but he does this for a living and he had been poisoned with mercury and cognitively he was failing he had tried everything he'd done chelation therapy he'd gone to eight hyperbaric centers around the world he hadn't improved and he called up and i said look maybe we can image you and see if i can get the dose right with you and he did i dosed him we treated him by 26 treatments he had made a substantial improvement and then he decided he'd go get some stem cells he went and got stem cells but then the next 11 days he got nine more hyperbaric treatments got himself up in the blue skies territory i call it with hyperbarics and he called up the stem cell place he said wow these stem cells they are great i am at the top of my game it's the best i've ever felt in the stem cell facility said look i i'm sorry we hate to pop your bubble but this is not our stem cells this was the hyperbarics we don't ever see a stem cell effect in less than 30 days what it was and nobody knew this but it was very likely the stem cells in the hyperbarics that we were facilitating implantation and that goes to the last finding that i want to talk about is so we're stimulating production release the stem cells from the bone area we're stimulating differentiation of them and maturation we're stimulating proliferation differentiation at the sites of injury in the brain and migration of it we're facilitating implantation of them if you exogenously administrate them administer them but we've now got some evidence we might even be increasing production i hope dr profile is going to talk about this because what happened was based on all the other stuff i showed you patients will call up and say you know we're also thinking of stem cells and i said well let me tell you we're now have some evidence that the hyperbaric oxygen is stimulating it may even help implantation so if you want to do that do some hyperbarics for and then we'll take a break right in the middle and you go get your stem cells come out and we're going to do them right afterwards just like these articles suggest and what ended up happening the patients started coming back from dr profrock's facility and said dr profrock said that we had more stem cells than he's been typically harvesting and i said oh that's kind of interesting well now we've got 12 patients in a row 11 or 12. i don't know he's going to give you the numbers but where there's almost three to four fold increase in adipose stem cells that he is harvesting and he's going to tell you about it because there's some other cheat and changes that are very interesting well how about that normal baric oxygen we did in the icu it turns out here is a study there's another one going on right now where they took rats and they gave them just room there or another group 40 oxygen which is oxygen by mask for two hours a day for 10 days and then they measured stem cells in the blood and inflammatory markers and what did they find in the hyperion group tnf alpha which is an inflammatory marker given off by white blood cells way down and guess what stem cells were released into the blood with just some supplemental oxygen again goes back to part of what we're doing well i've now done this with over 50 kids i really think it's up towards 70 or so in icus around the country and we're seeing about 90 of them respond and of course it helped take a little eden from where she was in bed and thrashing and that's a good picture of her before to you know walking and talking and so lastly and dr profrock's going to talk about is the 12 consecutive patients so the takeaways from this are what's hyperbaric oxygen i i'm going to tell you you probably know more about this than 75 percent of the doctors in the united states and i'm going to say probably 99 because none of them are taught anything about this gene expression stuff or anything you saw here today and it's all based all of those were scientific studies i showed you but it's increased pressure and increased oxygen to primarily treat wounding conditions even if we can't identify them as a wounding condition it treats the underlying disease processes it works by a lot of mechanisms but a dominant one is affecting our genes expressing and suppressing them and besides that gene activity we have a wide-ranging effect on stem cells somewhat depending on dose and that's going to get figured out in the years ahead but we're stimulating production release differentiation implantation and maybe even production of stem cells for harvest and likely when you combine these things together as we're now seeing in sequence it's additive and very likely synergistic all of these therapies together and the end result is brain repair thank you [Applause]