Pathophysiology of Stroke

Pathophysiology of Stroke

Stroke, a neurologic  disorder due to altered cerebral circulation. It  is the third leading cause of death .  there are many risk factors for stroke include hypertension, family history, and diabetes mellitus. The sub types of stroke are ischemia, infarction, and hemorrhage. Ischemia and infarction are the result of atherosclerotic development of thrombi and emboli. Decreased or absent cerebral circulation causes neuronal cellular injury and death. Intracerebral hemorrhage occurs from rupture of cerebral vessels which is mainly due to hypertension.                               The two major mechanisms which are mainly responsible for brain damagein stroke are,



The effects of ischemia are rapid because the brain does not store glucose(the chief energy substrate)

and is incapable of anaerobic metabolism.A thrombus or an embolus can occlude a cerebral artery and

cause ischemia in the affected vascular territory. Thrombosis of a vessel can result in artery-to-

artery embolism.

                         Normal cerebral blood flow (CBF) is approximately 50-to 60 ml/100g/ Min and varies in
different parts of the brain. when ischemia occurs, the cerebral auto regulatory mechanisms compensate for a
reduction in CBF by local vasodilatation, opening the collaterals, and increasing the supply of oxygen and
 glucose from the blood.Formation of microscopic thrombi is responsible for impairment of micro circulation in
cerebral arterioles and capillaries.Formation of a micro thrombus is triggered by ischemia-induced activation of
 destructive vasoactive enzymes that are released by endothelium, leucocytes, platelets and other neuronal cells.
At a molecular level,   hypoxic- ischemic neuronal injury is greatly influenced by “overreaction" of certain
  neurotransmitters, primarily glutamate and aspartate. This process called “excitotoxicity”  and is triggered
by depletion of cellular energy stores.Glutamate, which is normally stored inside the synaptic terminals,
is cleared from the extracellular space by an energy dependent process.The greatly increased concentration of
glutamate (and aspartate) in the extracellular space in a depleted energy state results in the opening of
 calcium channels associated with N-methy1-D-asapartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxanole
 propionate (AMPA) receptors. due to Persistent membrane depolarization causes influx of calcium, sodium,and
chloride ions and efflux of potassium ions. In addition to contributing to mechanical obstruction of
microcirculation,the leucocytes also activate vasoactive substances such as oxygen free radicals,
arachidonic acid metabolites (cytokines), and nitric acid.
                                                     The cellular effects of these mediators include
vasodilatation, vasoconstriction, increased permeability, increased platelets aggregation, increased
leukocyte adherence to the endothelial wall, and immunoregulation. Morphologically, endothelial cells swell and
form “microvilli” at the luminal surface of the cell. This results in a reduction in the luminal patency of the
capillary vessel.Activation of endothelial adhesion molecules promotes leukocyte adherence to the endothelial
 wall, a key process in the initiation of the inflammatory process.
                                   Within an hour of hypoxic- ischemic ,there is a core of infarction
surrounded by an oligemic zone called the ischemic penumbra (IP).The pathophysiology of IP is closely linked to
generation of spontaneouswaves of depolarization (SWD). SWD can originate from multiple foci.  Sustained increases of
synaptic glutamate and extracellular potassium ions are closely associated with the development of SWD.
Glutamate receptor antagonists that block trans membrane calcium flux and prevent intracellular calcium
accumulation are known to suppress SWD.  Hypoxic or rapid depolarizations eventually supervene just before
irreversible neuronal death.The two processes by which injured neurons are known to die are
  a)coagulation necrosis
  b) apoptosis.
                  Coagulation necrosis (CN) refers to a process in which individual cells die among living
neighbor cells without eliciting an inflammatory response.
                 apoptosis is also called “programmed cell death”, because the cells are programmed to
 die in response to certain conditions.