Cerebral Protection Strategies

Cerebral Protection Strategies Eddy M. Feliz, MD Boston University School of Medicine

Objectives • Define cerebral metabolism • Explain cerebral ischemia • Strategies to protect from cerebral ischemia

Cerebral Metabolism 2 components: • Functional – 60% O2 • Cellular integrity – 40% O2

Cerebral Ischemia • Metabolic demands > substrate delivery • Classification: • Focal • Global • Incomplete global

Cerebral Ischemia Neuronal death • Necrosis • Severe insult • High lactic acid concentration • Depleted ATP stores • Increased membrane permeability • Excessive release of excitatory neurotransmitters • Edema formation • Apoptosis • No edema formation • Requires regulating proteins • Caspase activation • Structural changes of membrane & DNA

Protection from Ischemia • Maintain normal cerebral perfusion pressure • Surgical evacuation of space occupying lesions • Normoxia • Reduce cerebral metabolism • Reduce intracranial pressure • Inhibit lactic acid accumulation • Inhibit lipid peroxidation • Inhibit free radical scavenging

Hypothermia • Reduction of brain temp when increased ICP or cerebral ischemia  neural protective • Suppression of major biochemical processes • Reduced neurological deficit and mortality • Hyperthermia  detrimental with cerebral ischemia • However, Hypothermia does not seem to be beneficial in brain injury secondary to cerebral aneurysm

Hyperglycemia • May worsen neurological outcome • Probably due to anaerobic metabolism of glucose • Poor outcome • Increased mortality • Best outcome: glucose 70-110mg/dl

Anesthetics IV anesthetics: • Most decrease CBF & CMRO2 • Suppress seizures & sympathetic discharge • Reset thermoregulatory threshold • May reduce intracellular Ca2+ • May reduce free radical accumulation • May inhibit glutamate toxicity • Don’t seem to affect brain response to CO2 **Except KETAMINE – increases CBF with smaller change in CMRO2

Anesthetics Inhalation agents: • Reduce CMRO2 • Direct vasodilator Opiods: • Don’t impair cerebral blood flow autoregulation

Anesthetics Isoflurane, sevoflurane, & desflurane: • Study (rats) • Seems to have neuroprotective effect • Decrease infarct size • Improved neurologic outcome • No benefit in preventing apoptosis • Benefits not proven clinically

Anesthetics Propofol & Barbituates: • Reduce ICP • Suppresses metabolism • Lower CBF and intracranial blood volume • Might increase ischemic tolerance of neurons

Anesthetics Etomidate: • Potent cerebral vasoconstrictor • Decreased CBF, CMRO2, ICP • Increases infarct size • Associated with seizures

Magnesium • Membrane stabilizer • Suggested protective mechanism: • Reduction of presynaptic release of glutamate • Blockade of NMDA receptors • Smooth muscle relaxation • Improved mitochondrial Ca2+ buffering • Blockage of Ca2+ entry • Protection depends on: • Time of treatment initiation • Type of cerebral ischemia • Benefit in neocortical stroke

Osmodiuretics • First line treatment to decrease high ICP • Induce plasma expansion • Reduced hematocrit • Reduced plasma viscosity • Reduced CBV • Mobilization of ECF • Early high does of mannitol shown to improve long term outcomes

Statin • Inhibits 3-hydroxy 3-methygluraryl coenzyme A reductase • Increase endothelial nitric oxide • Reduce oxidative stress • Anti-inflammatory effect • Plaque stabilization • Shown to decrease rate of ischemic stroke by 30% • Further investigation needed!

Glucocorticoids • Suggested protective mechanisms: • Increase lipid bilayer • Free radical scavenging • Reduces cerebral edema • Anti-inflammatory effects • Prevents FFA accumulation • Inhibits lipid peroxidation • Not shown to decrease morbidity of mortality in acute cerebral ischemia • Not recommended for head trauma • Methylprednisolone: mild benefits in acute spinal cord injury • Beneficial with brain tumors

The End

Cerebral Protection Strategies