Brain requires D-glucose and O2 for energy 

Requires continuous supply, 20% cardiac output

Glucose cannot cross BBB, uses transporter

Can only go down BBB 

"Luxury perfusion"

Requires 2 molecules of ATP to initiate process and yields 4 molecules for ATP for a 

Net Gain of 2 ATP

For every 2 molecules of acetyl CoA that enters the cycle; 4 molecules of carbon dioxide are liberated and excreted by the lungs

yields 2 GTP 

Energy stored in the coenzymes is transferred to ADP and inorganic phosphate to ATP

Yields 34 ATP 

Blockage of oxidative phosphorlyation-decreased ATP production (95%)

Gluose supply is interupted, washout of metabolite is interrupted 

ATP-dependent pump activity is decreased which causes neurons to depolarize 

Depolarization releases glutamate causing further depolarization 

Calcium influx, swells nerve cells, destroys mitochondria 

Free radical forms 

Damage proteins and lipids

Free fatty acids interfere with membrane function

Form from decrease in pH from lactate and hydrogen ions 

Leads to excess arachidonic acid production

Reoxygenation can form: dicosanoids, thromboxane, prostaglandins, leukotrienes 

Cause vasoconstriction, reduce blood flow in the post-ischemic period, alter the BBB and enhance free radical formation after reperfusion 

Vasospasm

Red Cell Sludging 

Hypoperfusion 

ATP reduction

Sodium influx, calcium influx 

Potassium eflux

Intracellular acidosis

Capase and Phospholipase activation

Arachidonic acid formation and breakdown 

Free radical production

Excitatory amino acid release 

Severe insult in which mitochondria loses function

Activation of microglia and immune response

Produce free radicals and damage adjacent neurons 

Cell dies without breaking apart

Activation and release of certain cytokines, such as tumor necrosing factor and interleukin-1B are though to be damaging 

Pneumbra receives collateral flow and is partially ischemic 

Reestablishment of blood flow is critical 

Normally perfused 

Very short ischemic times are survivable 

Noncontrast CT should be done prior

TPA within first 3-4.5 hours

Warfarin 

Recanulization for mechanical removal of clots 

Major side effect is intracerebral hemorrhage 

Target 32-34 degrees C

After cardiac arrest improves neurologic outcome and survival 6 months after the arrest

Decreases CMRO2, excitatory neurotransmission

Delays anoxic/ischemic depolarization

Prevention/reduction of damaging biochemical changes 

Myocardial Depression

Dysrhythmias

Hypotension

Decreased tissue perfusion

Ischemia

Thrombocytopenia

Fibrinolysis 

Platelet dysfunction

Increased bleeding 

Slowed Metabolism of anesthetic agents

Prolonged nm blockade

Increased protein catabolism 

Increased O2 consumption

Increased CO2 production

Increased cardiac output

Arterial oxygen desaturation 

Hemodynamic instability 

Worsening of damage with hyperglycemia due to cellular acidosis 

Precise mechanism unclear as to why this happens

Keep blood sugar within normal range

Sodium influx blockade during anoxia and ischemia improves recovery 

Delays depolarization and delays the drop in ATP during anorexia and ischemia

Lidocaine has been shown to improve recovery by delaying the anoxic/ischemic depolarization- improves the survival of CA1 pyramidal neurons

Cognitive task that required hippocampal involvement 

Recommended for hypertension, hypervolemia, and hemodilution to treat vasospasm 

Nimodipine has been shown improved recovery after subarachnoid hemorrhage 

Resently shown to be benefit during focal cerebral ischemia 

Reduces NMDA receptor activation

Thought to cause cellular damage and neuronal damage after ischemia

NXY-059, Alpha-Tocopherol (VitE), PBN, Tirilazad

Methylprednilsone for 48 hours after spinal cord injury 

Neither methylprednisolone nor tirilazad noted improvement after cortical trauma or any ischemic lesion

Causes immune system suppression, increase infection 

Thought to enhance neuronal damage

Lubeluzole (nitric oxidie formation inhibitor) not found to benefit patients with ischemia 

Excitatory amino acids implicated in damaging cascade following ischemia, trauma, epilepsy

Glutamate receptor blockers have been found to be toxic themselves and may cause neuronal damage

Improves blood cell production, also present in the nervous system

Reguarding neuronal protection during hypoxic conditions

May protect neurons for apoptosis after ischemia by activating the trophic factor apoptotic pathway 

Ability to improve recovery from ischemia 

Reduce neuronal activity and metabolic rate 

Should lower energy demand, enhance energy supply, attenuate ischemic damage 

Only anesthetic shown to be neuroprotective- blocks Na, K, and Ca fluxes

Scavenges free radicals, blocks seizures, improves regional blood flow, decreaes ICP 

Brevital is used at CMC 

Reduces cerebral metabolic rate in burst supression doses

Does not improve recevory from ischemia and anoxic damage

May reduce ischemic damage

cannot be assumed that it will provide the same cerebral protection as thiopental

Enhance neuronal inhibition

Reduces brain metabolism

Enhances neuronal inhibition in the nervous system

High dose versed has been shown to reduce cerebral metabolism and cerebral blood flow

Improves neuronal recovery after anoxia and ischemia 

Better outcome than fentanyl-nitrous anesthesia

Allows rapid-awakening to evaluate neurological fx 

Reported to have neuroprotective effects

Improves recovery in brain slices

At equal MAC Sevo was more effective than isoflurane 

Sudden synchronus discharges of large numbers on neurons

Seen in Disorders of brain metabolism, infection, brain tumor, brain trauma, elevated body temperature 

EEG shows spikes in voltage

Cells use more energy ATP for ion pumping, High K responsible for large progressive depolarization

Enhanced excitability causes glutamate release and excitotoxicity and exacerbate damage 

Intracellular calcium levels rise, precipitating the damage

Energy demand and CMR and blood flow rise greatly

Avoid excess brain activity 

Treat: Lactic acidosis, reduce arterial oxygenation, increased carbon dioxide

Benzos, Barbiturates, Anticonvulsants

In combination with ischemia, sz can cause rapid and devastating neuronal damage 

Head trauma can lead directly to permanent physical neuronal damage

Direct neuronal injury, Brain herniation, Serving blood vessels

Occurs after the injury, calcium influx implicated as trigger for the damage

Prevent secondary ischemia d/t release of vasoconstrictive substances during reperfusion 

CPP=MAP - ICP

Treat ICP which can hypoperfusion of the brain 

Diuretics to remove excess fluid from the brain 

May increase intracranial blood volume raising ICP

Reduce cerebral perfusion pressure

Intracranial blood promoting free radical formation

Seconday damage may reduce with proper monitoring, hypotension should be avoided 

Lower ICP

Maintain blood flow

Reduce vasospasm

Remove blood from the subarachnoid space

Prevent neruonal damage

High dose corticosteroids

Magnesium

Nimodipine