stroke: an acute and treatable condition thomas g. bowers, ph.d
TRANSCRIPT
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
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
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
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