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Brain Attacks Add Corporate Logo Here CVA Cerebral Vascular Accidents • Now referred to as strokes or brain attacks • Acute and treatable condition • Third leading cause of death • Leading cause of disability CVA • Mortality – 1. Heart disease 33.2% – Cancer 23.7% – CVD 6.6% CVA • Basic information – Males have more strokes – Females>Males over age 85 CVA • Mortality by Race – Age adjusted • White • Black 22.5 per 10,000 48.9 per 10,000 • Morbidity – Prevalence 2.9 million in 1991 – Cost $30 billion per year CVA • Mechanisms – Anoxia – CA+ influx – Excitatory amino acids – Free radicals CVA • Morphology – Penumbra develops – Region of encapsulated cells, alive but not well CVA • Some treatment methods – Surgical clinical trials - carotid ectomy – Woman’s Estrogen Trials (WEST) – Prevention by aspirin – Neuron salvage agent Carotid Arteries CVA • Long term results – Revascularization • local factors increase blood levels – Neural plasticity and regeneration – Recurrent strokes CVA • Ischemic cell damage (Choi) – Cells are stimulated to death – Glutamate neurotoxicity – Cycle of hypoxia, hypoglycemia, ischemia CVA • Glutamate neurotoxicity – Energy depletion – Glu increase – Uptake of glu – Toxic glu exposure – Cell death – Glu release CVA • Glutamate cell death – Cellular swelling – Cell death in under 5 minutes CVA • Other Mechanism – High rates of Ca+ entry into cell – AMPA yields Na+ – MMDA yields Ca+, Na+ – AMPA toxicity after 3+ hours – Yields 70% cell death – 24 hours yields 100% cell death CVA • Process – Induction – Amplification – Expression CVA • Hypoxic injury to brain – Bulbous swelling of the dendrites – Swelling of the cell body – MK801 (Ca+ blocker) greatly slows cell death – MMDA antagonistic CVA • Cardiac Arrest Victims – “Window of Opportunity” – Histopathology – Heart attack - the entire brain becomes ischemic Neurohistopathology Neuron glu Lactate CO2 O2 CVA • Decreasing order of vulnerability to ischemia – Neurons – Support cells – Astrocytes – Endothelial cells CVA • Vulnerable regions – Decreasing order of sensitivity • • • • 1. 2. 3. 4. Hippocampus Cerebellum Stratum Neocortex CVA • Vulnerable regions – Hippocampal cells may live 24-72 hours – CA1 > CA3 resistant to anoxia – CA1 24-48 hours CVA • Syndromes – Transitant Ischemic Attack (TIA) – Resolving Ischemic Neurological Deficits (RIND) – Stroke CVA • Common patterns – 1. Middle cerebral artery occlusion – Redundancy in the neurovascular system – Circle of Willis Circle of Willis CVA • Some principles – “Time is brain” – Focal symptoms • “Fit” • Migraine • “Swoon” CVA • Some principles – Non-Focal symptoms • syncope • hypoglycemic • “Toxic” CVA • Types of CVA – Hemorrhage • Subarachnoid (vomiting, back of head, blood in CSF) • Intracerebral (focal onset, gradual increase in signs) CVA • Types of CVA – Ischemic • Thrombosis • Embolism • Systemic hypertension