Overview
This lecture covers the mechanisms of brain injury, focusing on the effects of impaired blood flow and oxygen delivery on neurons, and discusses primary and secondary injuries, cellular responses, and treatment principles.
Mechanisms of Brain Injury
- Brain injuries often result from disrupted blood flow (ischemia) or oxygen supply, leading to cellular dysfunction.
- Causes include mechanical trauma, ischemia, energy failure, apoptosis, and reperfusion injury.
- Injuries are classified as primary (immediate/acute) or secondary (delayed/gradual).
Primary vs Secondary Injury
- Primary injury: occurs instantly after the event (e.g., stroke, trauma), with little opportunity for intervention.
- Secondary injury: develops over hours to months, often involves apoptosis and additional cell damage.
Neuronal Response to Ischemia
- Ischemia leads to reduced ATP, forcing cells into anaerobic metabolism, producing lactic acid and causing acidosis.
- ATP deficiency disrupts ion gradients, particularly sodium-potassium pumps, resulting in abnormal ion flows and neuronal depolarization.
- Loss of ATP causes abnormal calcium levels, impairs neurotransmitter synthesis, and increases excitatory neurotransmitter exposure (notably glutamate).
Cellular Pathology
- Elevated intracellular calcium signals apoptosis and activates enzymes (phospholipases) that irreversibly damage cell membranes.
- Excess glutamate over-activates AMPA and NMDA receptors, allowing sodium and calcium influx, leading to cytotoxic edema.
- Impaired glutamate reuptake perpetuates excitotoxicity and neuron damage.
Reperfusion Injury
- Restoring blood flow after ischemia can cause reperfusion injury via inflammation, free radical generation, and apoptosis.
- Neurons are highly susceptible due to high oxygen demand and low antioxidant capacity.
Autoregulation of Cerebral Blood Flow
- Autoregulation maintains stable blood flow based on CO2, O2, and pH levels.
- Hypotension (low BP) leads to ischemia; hypertension (high BP) risks vessel damage and brain edema.
- Vessels dilate in response to low BP/high metabolic demand and constrict with high BP/low demand.
COâ‚‚ and Blood Flow Regulation
- Rising arterial COâ‚‚ (PaCOâ‚‚) leads to vasodilation and increased brain blood flow.
- Hyperventilation lowers PaCOâ‚‚, causing cerebral vasoconstriction and temporarily lowering intracranial pressure (ICP).
- Prolonged hyperventilation reduces brain blood flow, risking further ischemia.
Strategies to Reduce Metabolic Demand
- Treatment aims to reduce neuronal metabolic demand to protect against injury.
- Methods include inducing hypothermia, encouraging rest, pain control, seizure management, lesion removal, and reducing edema.
Key Terms & Definitions
- Ischemia — reduced blood supply to tissues.
- Apoptosis — organized, energy-dependent programmed cell death.
- Necrosis — uncontrolled, messy cell death due to acute injury.
- Cytotoxic edema — cell swelling from disrupted ion/water balance.
- Excitotoxicity — neuron injury/death caused by excessive excitatory neurotransmitters (e.g., glutamate).
- Reperfusion injury — tissue damage from restored blood flow after ischemia.
- Autoregulation — brain's mechanism to maintain consistent blood flow despite systemic changes.
Action Items / Next Steps
- Review relevant lecture materials on neural metabolism, neurotransmission, and pathology.
- Prepare for upcoming units on specific neurological pathologies (e.g., stroke, Alzheimer’s, Parkinson’s).
- Complete assigned readings on brain injury mechanisms.