الفهرس 
Pathophysiology of Cerbrovascular Stroke
Early events in the surviving penumbraOnly 14 pages are availabe for public view
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Abstract
Stroke is the third leading cause of death following heart
diseases and cancer, approximately 20-25% of these people will
die within 1 year of their stroke, also it is the most common cause
of adult disability. Despite advances in acute and prophylactic
therapies, rates of stroke and stroke-related deaths continue to
increase. Stroke occurs when the blood supply to a part of the
brain is suddenly interrupted or when a blood vessel in the brain
bursts, spilling blood into the spaces surrounding brain cells. An
exceptional character of the brain is that more any other organ the
brain depends from minute to minute to an adequate supply of
oxygenated blood. Understanding the exacts pathophysiological
events that happen following disruption of cerebral blood flow
and the ischemic cascade which is followed by series of steps
leading to neuronal death. Aprupt deprivation of oxygen and
glucose to neuronal tissues elicits a series of pathological
cascades, leading to spread of neuronal death. Of the numerous
pathways identified, excessive activation of glutamate receptors,
accumulation of intracellular calcium cations, abnormal
recruitment of inflammatory cells, excessive production of free
radicals, and initiation of pathological apoptosis are believed to
play critical roles in ischemic damage, especially in the penumbral
zone. Thus, it is logical to suggest that if one is able to interrupt
the propagation of these cascades, at least part of the brain tissue
can be protected. Spontaneous neuroplasticity triggered after
stroke. Injury causes the activation of numerous factors that
impede plasticity, among them are several chemokines and cytokines involved in inflammatory reaction. Ex. Treatments
inhibiting cyclooxygenases enhance poststroke plasticity.
However, some elements of inflammatory cascade can improve
recovery. Since post ischemic inflammation is associated not only
with ischemic damage but also with the repair of injured brain
tissue, the most important aspect of therapies targeting the
immune system will be to regulate the balance between the
neurotoxic and neuroprotective effects of inflammatory state
components. Brain plasticity refers to the brain ability to change
its structure and function during maturation, learning,
environmental changes and pathology. Altogether, brain plasticity
ultimately involves all the mechanisms implicated in the capacity
of the brain to adjust and remodel itself in response to
environmental requirements, experience, skill acquisition and new
challenges including brain lesions. For example, starting within
the minutes following ischemia, rapid changes are observed in the
number and the length of dendritic spines. Using neuroimaging
techniques provides a basis for bridging the gap between clinical
practice and the neural representation of recovery mechanisms in
the brain, leading to new physical rehabilitative therapies. In
providing information on the excitability, extension, and
localisation of motor cortex areas during recovery, functional
imaging plays an important role for viewing possibilities of
functional reorganization. Functional imaging data also has told
us that a focal stroke lesion may affect not only the lesion site but
also the network to which it belongs. Thus the connectivity-based
analytic methods may be more appropriate for elucidating stroke
induced impairments from a network perspective and for clarifying the mechanisms of motor recovery after stroke.
Moreover, connectivity analyses are likely to be better suited to
investigate the mechanisms through which therapeutic
interventions may facilitate the recovery of motor function and
help us to develop new intervention therapies targeting the
restoration of the function of the motor network. So, connectivity
measures may serve to monitor the process of stroke recovery and
to predict the outcomes of stroke patients at an early stage.
Most protocols for stroke rehabilitation are based on motor
learning, which induce dendrite sprouting, new synapse formation,
alterations in existing synapses, and neurochemical production.
These changes are thought to provide a mechanistic substrate to
facilitate motor recovery after stroke. Motor learning is known to
be greater if the practice method is meaningful, repetitive, and
intensive. Additionally, the constraint-induced therapy can
producer organizational effects not only in acute stroke patients,
but also in chronic stroke patients, suggesting that the motor
cortex retains a capacity for recovery through plasticity over a
long period of time after the lesion occurred.
Brain remodelling after stroke and subsequent improvement
of functional outcome probably result from several restorative
events that are enhanced by restorative therapies. Induction of
angiogenesis couples with and promotes neurogenesis and
neuroblast migration to the lesion. These interlinked remodelling
events could create a microenvironment within the injured brain
through their interaction with astrocytes and oligodendrocytes,
which then promote neurite outgrowth and plasticity within the brain and spinal cord. These restorative events enhanced by
restorative cell-based and pharmacological therapies lead to
improved functional outcome. Cell-based therapy has been
investigated as an alternative strategy to improve neurological
outcome after ischemic stroke for more than a decade. Reports
from preclinical rodent models of ischemic stroke and clinical
trials using stem cells or adult and fetal progenitor cells have
shown therapeutic promise.