Stroke Pathophysiology

Figure 6-1
Pathway of cerebral ischemia
  • Reduction in blood flow:
    • Cerebral ischemia develops when CBF is reduced to <22 ml/100 g/min
    • <10 ml/100 g/min leads to infarct
  • Energy failure:
    • Diminished CBF leads to metabolic stress and depletion of energy stores (ATP, phosphocreatine)
    • Leads to breakdown of ion gradients, lipolysis, proteolysis, lactic acidosis in infarct core, accumulation of oxygen free radicals
  • Cell membrane depolarization and Na+/K+ pump dysfunction
    • Large Na, Cl influx leads to passive water influx into cell leads to development of cytotoxic edema
      • Cell membranes are unable to counteract cell swelling due to pump failure
      • Increased signal can be seen on early MRI scans representing restricted diffusion of water due to edema
    • Increased efflux of intracellular K
      • Increased release of Glu from presynaptic terminals into synaptic cleft and failure of Glu re-uptake from synaptic cleft (concentrations increased 150x)
      • Glu → Excessive stimulation of NMDA receptors → excessive Ca++ influx
      • Glu → ++inward fluxes of Na + and Ca++ → cell swelling
      • Increased intracellular calcium activates phospholipases and proteases (matrix metalloproteinases), degrading basal lamina, leading to BBB breakdown and triggering excitotoxic cell death
  • Cell Death
    • Occurs either via necrosis or apoptosis
    • Necrosis : cell death when energy stores (ATP) are depleted
      • More often found at infarct core due to lower ATP levels compared to periphery (or penumbra)
      • Causes cell swelling and rupture of membranes, leading to cellular material being deposited into surrounding environment, triggering an inflammatory cascade
    • Apoptosis : regulated, energy-dependent, programmed cell death, usually occurs in periphery (where ATP levels are higher)
      • Occurs by increased mitochondrial permeability, “death receptor” Fas pathway, systematic cellular degradation and phagocytosis
    • The longer the duration of ischemia, the higher the likelihood of cell death by neuronal necrosis than apoptosis
    • Excessive amounts of zinc released from excitatory neurons also contributes to cell death
  • Cortical spreading depression
    • Cells at core of lesion remain depolarized and can propagate sustained waves of depressed electrical activity (cortical spreading depression) in nearby tissue
    • Leads to further release of glutamate → excitotoxicity

      Cerebral Autoregulation

      • Mechanism of responding to changes in cerebral perfusion pressure (CPP) by altering vascular tone, with a goal of maintaining a consistent level of CBF (Fig. 6-2)
        A330798_1_En_6_Fig2_HTML.jpg
        Figure 6-2
        Cerebral autoregulation
        • Low BP (low CPP) → vasodilation
        • High BP (high CPP) → vasoconstriction
      • Cerebral Perfusion Pressure (CPP): An estimate of mean arterial pressure (MAP) under normal intracranial pressure (ICP) conditions
        • CPP = MAP – ICP
        • Normal range is 50–150 mmHg in nonhypertensive person
        • Mean Arterial Pressure (MAP): an estimate of cerebral perfusion pressure
          • Increased MAP → vasoconstriction and increased vascular resistance to maintain CBF over a wide range
          • When MAP is beyond the upper limit of autoregulation , this leads to increased vessel permeability → forced dilation, autoregulatory breakthrough
            • Hypertensive encephalopathy, hemorrhage, cerebral edema, raised intracranial pressure (ICP)
          • When MAP falls below the lower limit of autoregulation , this leads to impaired dilation and arterial collapse
      • Cerebral Blood Flow (CBF ): Rate of blood flow through brain parenchyma at a given time
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      Oct 7, 2017 | Posted by in NEUROLOGY | Comments Off on Stroke Pathophysiology

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