الفهرس | Only 14 pages are availabe for public view |
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. |