Stroke:Stroke:An Acute and Treatable An Acute and Treatable

ConditionCondition

Thomas G. Bowers, Ph.D.Thomas G. Bowers, Ph.D.

An OverviewAn Overview

Used to be referred to as a cerebral Used to be referred to as a cerebral vascular accident (CVA)vascular accident (CVA)

Better referred to as a “brain attack” Better referred to as a “brain attack” Sudden onset, apoplexy Sudden onset, apoplexy

Basic InformationBasic Information

Third leading cause of mortalityThird leading cause of mortality– 2.9 prevalence in 19912.9 prevalence in 1991– Heart disease 33.2%Heart disease 33.2%– Cancer 23.7%Cancer 23.7%– CVD 6.6%CVD 6.6%

Leading cause of disabilityLeading cause of disability– Cost ~$30 billion year in 1990sCost ~$30 billion year in 1990s

These estimates are probably low, as These estimates are probably low, as “silent strokes” can also occur“silent strokes” can also occur

Risk FactorsRisk Factors

AgeAge GenderGender ObesityObesity Lack of exerciseLack of exercise HypertensionHypertension Tobacco smokingTobacco smoking ETOH intakeETOH intake

Risk FactorsRisk Factors

CortisolCortisol StressStress Males>FemalesMales>Females

– Until women are older (>85)Until women are older (>85) Blacks>WhitesBlacks>Whites

– Age adjusted x 10Age adjusted x 1033

– White 22.5, Black 48.4White 22.5, Black 48.4

What happens at the cellular What happens at the cellular level?level?

Ischemic cell damage occursIschemic cell damage occurs– Brain is especially sensitive to anoxiaBrain is especially sensitive to anoxia– Cells are stimulated to deathCells are stimulated to death

Glutamate neurotoxicityGlutamate neurotoxicity– Progression from hypoxia to Progression from hypoxia to

hypoglycemia and ischemia hypoglycemia and ischemia

Glutamate ToxicityGlutamate Toxicity

Energy depletion

Glucose uptake

Increased glucose

Cell Death

Glutamate ToxicityGlutamate Toxicity

Glutamate leads to cell death, Glutamate leads to cell death, cellular swellingcellular swelling

Rapid – cell death to Glu excitation Rapid – cell death to Glu excitation can occur in less than five minutescan occur in less than five minutes

Also allows high rates of Ca+ entry Also allows high rates of Ca+ entry into the neuron.into the neuron.

Glutamate ToxicityGlutamate Toxicity

Additional processes occurAdditional processes occur Ischemia is fundamentally Ischemia is fundamentally

depolarizing for the celldepolarizing for the cell

AMPA

NMDA

Metabotoxins

Leads to an infusion of Ca+ and Na+

AMPA ToxicityAMPA Toxicity

Occurs after about 3+ hours of Occurs after about 3+ hours of ischemic exposureischemic exposure

Yields 70% cell deathYields 70% cell death 24 hours yields 100% cell death 24 hours yields 100% cell death

SummarySummary

Process of Ischemic AttackProcess of Ischemic Attack

Induction

Amplification

Expression

Cellular Effects of Hypoxic Cellular Effects of Hypoxic InjuryInjury

Bulbous swelling on the dendritesBulbous swelling on the dendrites Swelling of the cell bodySwelling of the cell body Treatment with Ca+ blockersTreatment with Ca+ blockers

Some Trials on Ca+ Some Trials on Ca+ blockersblockers

0102030405060708090

45 60 75 120

Minutes

% C

ell D

eath

Line 2Line 3

Penumbra EffectPenumbra Effect

Penumbra

Core<O2

Ph 6.4<<ATP

Histopathology of IschemiaHistopathology of Ischemia

With a heart attack, the entire brain With a heart attack, the entire brain becomes ischemicbecomes ischemic

After 2-3 minutes, cellular energy After 2-3 minutes, cellular energy pumps fail pumps fail

Histopathology of IschemiaHistopathology of Ischemia

Cell

Blood Vessel

Blood brain barrierBlood brain barrier

Histopathology of IschemiaHistopathology of Ischemia

Blood Vessel

Glucose o2 Lactate CO2

Decreasing Order of Decreasing Order of Vulnerability to IschemiaVulnerability to Ischemia

NeuronsNeurons OligondendroglialOligondendroglial AstrocytesAstrocytes Endothelial cellsEndothelial cells

Decreasing Order of Sensitivity Decreasing Order of Sensitivity in Vulnerable Regionsin Vulnerable Regions

HippocampusHippocampus CerebellumCerebellum StriatumStriatum NeocortexNeocortex

VulnerabilityVulnerability

Hippocampal cells may live 24-72 Hippocampal cells may live 24-72 hourshours

Ascending level of clinical Ascending level of clinical severityseverity

Transient Ischemic Attack Transient Ischemic Attack (TIA)(TIA)

Resolving Ischemic Resolving Ischemic Neurological Deficits (RIND)Neurological Deficits (RIND)

StrokeStroke

Clinical Diagnosis Clinical Diagnosis

Important in emergency medicine Important in emergency medicine

Clinical Diagnosis Clinical Diagnosis

FocalFocal– A “fit”A “fit”– MigraineMigraine– TumorTumor– ““Swoon”Swoon”

Clinical Diagnosis Clinical Diagnosis

Non focalNon focal– SyncopeSyncope– HypoglycemiaHypoglycemia– ToxicityToxicity

Clinical Diagnosis Clinical Diagnosis

If CVAIf CVA– HemorrhageHemorrhage

Subararchoid Subararchoid IntracerebralIntracerebral

– IschemiaIschemia ThrombosisThrombosis EmbolismEmbolism

– Cardiac?Cardiac?– Intra cerebral?Intra cerebral?

Systemic hyper fusionSystemic hyper fusion

Clinical Diagnosis Clinical Diagnosis

Common sourcesCommon sources– Middle cerebral arteryMiddle cerebral artery– Basilar arteryBasilar artery