Stroke: An Acute and Treatable Condition Thomas G. Bowers, Ph.D.

An Overview Used to be referred to as a cerebral vascular accident (CVA) Used to be referred to as a cerebral vascular accident (CVA) Better referred to as a “brain attack” Better referred to as a “brain attack” Sudden onset, apoplexy Sudden onset, apoplexy

Basic Information Third leading cause of mortality Third leading cause of mortality –2.9 prevalence in 1991 –Heart disease 33.2% –Cancer 23.7% –CVD 6.6% Leading cause of disability Leading cause of disability –Cost ~$30 billion year in 1990s These estimates are probably low, as “silent strokes” can also occur These estimates are probably low, as “silent strokes” can also occur

Risk Factors Age Age Gender Gender Obesity Obesity Lack of exercise Lack of exercise Hypertension Hypertension Tobacco smoking Tobacco smoking ETOH intake ETOH intake

Risk Factors Cortisol Cortisol Stress Stress Males>Females Males>Females –Until women are older (>85) Blacks>Whites Blacks>Whites –Age adjusted x 10 3 –White 22.5, Black 48.4

What happens at the cellular level? Ischemic cell damage occurs Ischemic cell damage occurs –Brain is especially sensitive to anoxia –Cells are stimulated to death Glutamate neurotoxicity Glutamate neurotoxicity –Progression from hypoxia to hypoglycemia and ischemia

Glutamate Toxicity Energy depletion Glucose uptake Increased glucose Cell Death

Glutamate Toxicity Glutamate leads to cell death, cellular swelling Glutamate leads to cell death, cellular swelling Rapid – cell death to Glu excitation can occur in less than five minutes Rapid – cell death to Glu excitation can occur in less than five minutes Also allows high rates of Ca+ entry into the neuron. Also allows high rates of Ca+ entry into the neuron.

Glutamate Toxicity Additional processes occur Additional processes occur Ischemia is fundamentally depolarizing for the cell Ischemia is fundamentally depolarizing for the cell AMPA NMDA Metabotoxins Leads to an infusion of Ca+ and Na+

AMPA Toxicity Occurs after about 3+ hours of ischemic exposure Occurs after about 3+ hours of ischemic exposure Yields 70% cell death Yields 70% cell death 24 hours yields 100% cell death 24 hours yields 100% cell death

Summary Process of Ischemic Attack Process of Ischemic Attack Induction Amplification Expression

Cellular Effects of Hypoxic Injury Bulbous swelling on the dendrites Bulbous swelling on the dendrites Swelling of the cell body Swelling of the cell body Treatment with Ca+ blockers Treatment with Ca+ blockers

Some Trials on Ca+ blockers

Penumbra Effect Penumbra Core <O 2 Ph 6.4 <<ATP

Histopathology of Ischemia With a heart attack, the entire brain becomes ischemic With a heart attack, the entire brain becomes ischemic After 2-3 minutes, cellular energy pumps fail After 2-3 minutes, cellular energy pumps fail

Histopathology of Ischemia Cell Blood Vessel Blood brain barrier

Histopathology of Ischemia Blood Vessel Glucose o2o2 Lactate CO 2

Decreasing Order of Vulnerability to Ischemia Neurons Neurons Oligondendroglial Oligondendroglial Astrocytes Astrocytes Endothelial cells Endothelial cells

Decreasing Order of Sensitivity in Vulnerable Regions Hippocampus Hippocampus Cerebellum Cerebellum Striatum Striatum Neocortex Neocortex

Vulnerability Hippocampal cells may live hours Hippocampal cells may live hours

Ascending level of clinical severity Transient Ischemic Attack (TIA) Transient Ischemic Attack (TIA) Resolving Ischemic Neurological Deficits (RIND) Resolving Ischemic Neurological Deficits (RIND) Stroke Stroke

Clinical Diagnosis Important in emergency medicine Important in emergency medicine

Clinical Diagnosis Focal Focal –A “fit” –Migraine –Tumor –“Swoon”

Clinical Diagnosis Non focal Non focal –Syncope –Hypoglycemia –Toxicity

Clinical Diagnosis If CVA If CVA –Hemorrhage  Subararchoid  Intracerebral –Ischemia  Thrombosis  Embolism –Cardiac? –Intra cerebral?  Systemic hyper fusion

Clinical Diagnosis Common sources Common sources –Middle cerebral artery –Basilar artery