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Two main mechanisms may lead to ischaemic stroke: occlusive or haemodynamic. These two
situations decrease the cerebral perfusion pressure and eventually lead to cellular death. But within certain limits,
the brain blood flow can be maintained by autoregulation of cerebral arteries and collateral circulation. When occlusion
of an artery develops, blood flow in the periphery of the infarct core is usually reduced but still sufficient to
avoid structural damage, so that the functional modifications of cells may be reversible if circulation is
restored. This ring-like area of reduced blood flow around the ischaemic centre of infarct has been termed
penumbra as an analogy of the half-shaded part around the centre of a solar eclipse. It may largely explain the
functional improvement occurring after stroke. Indeed, the neurons surviving in this critical area of infarct at
reduced blood flow may again function as soon as blood flow and oxygen delivery is restored (www.eusi-stroke.com).
Reference:
EUSI Recommendations. 2002, www.eusi-stroke.com.
Reference:
MacWalter RS, Merrylees C. www.dundee.ac.uk/medicine/StrokeSSM/StrokeAdvancesinAcute Management/ sld015.htm.
 
Biochemical Cascade
Within the last decade, researchers have learned exactly why brain cells die during stroke. Most
strokes culminate in a core area of cell death (infarction) in which blood flow is so drastically reduced that the cells
usually cannot recover. This threshold seems to occur when cerebral blood flow is 20% of normal or less.
Without neuroprotective agents, nerve cells facing 80 to 100% ischaemia will be irreversibly damaged within a few minutes.
Surrounding the ischaemic core is another area of tissue called the "ischaemic penumbra" or "transitional zone" in which
cerebral blood flow is between 20 and 50% of normal. Cells in this area are endangered, but not yet irreversibly damaged.
Rapidly within the core infarction, and over time within the ischaemic penumbra, brain cell injury and death progress in
this way:
- Without adequate blood supply, brain cells lose their ability to produce energy - particularly adenosine triphosphate (ATP).
- When this energy failure occurs, brain cells become damaged and will die if critical thresholds are reached.
Mechanisms Causing Brain Cell Damage
Researchers believe there are an immense number of mechanisms at work causing brain cell damage and death following energy
failure. Each of these mechanisms represents a potential route for intervention.
One of the ways brain cells respond to energy failure is by elevating the concentration of intracellular calcium. Worsening
this and driving the concentrations to dangerous levels is the process of excitotoxicity, in which brain cells release
excessive amounts of glutamate, a neurotransmitter. This stimulates chemical and electrical activities in receptors on
other brain cells, which leads to the degradation and destruction of vital cellular structures.
Brain cells ultimately die as a result of the actions of calcium-activated proteases (enzymes which digest cell proteins),
lipases (enzymes which digest cell membranes) and free radicals formed as a result of the ischaemic cascade
(www.eusi-stroke.com).
References:
MacWalter RS, Merrylees C. www.dundee.ac.uk/medicine/StrokeSSM/StrokeAdvancesinAcute Management/ sld016.htm. |
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© 2005 Boehringer Ingelheim GmbH, Germany. All rights reserved.
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