Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke (original) (raw)
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Cytokines and Reperfusion in Ischemic Stroke
Brain Pathology, 1997
The clinical syndrome known as Ischemic stroke, secondary to the occlusion of an intracranial artery, once considered an ineluctably catastrophic event, may be susceptible of being improved thrgugh the application of newly developed therapeutic interventions. The evidence favoring this optimistic outlook is based on three separate but probably interrelated observations: (1) There exists a lapse of hours, perhaps days, between the ictus (i.e., the appearance of a focal neurologic deficit or stroke) and the time when irreversible tissue injury (i.e., widespread pannecrosis) becomes demonstrable. This time lnter-Val, generally known as the therapeutic window, may be measured in hours or days depending on the degree or severity of the post occlusive ischemia. (2) Reopening the artery, within a reasonable period of time, has beneficial effects in terms of: (a) improving the neurologic function, and (b) decreasing the numbers of necrotic neurons as well as preventing the appearance of pannecrosis or infarction. (3) The progression from the early ischemic changes (potentially reversible) to the development of an infarct may be Influenced by the effects of selected cytokines, in particular those of interleukin 1 (IL-1). In this review we illustrate selected structural features of the various brain lesions induced by either permanent or transient arterial occlusions. Moreover, we discuss the possible Involvement of interleukins in the progression of the brain lesion based on experiments utilizing the administration of a human recombinant 1L-1 receptor antagonist. Combined with the efforts aimed at restoring the normal circulatory conditions, therapeutic interventions that inhibit specific cytokines may contribute to improve the outcome of ischemic strokes.
New and investigational treatment options for ischemic stroke
Pharmacotherapy
We conducted a MEDLINE search of new treatment strategies and experimental agents for treating acute ischemic stroke published from 1989-1996. Clinical trials involving thrombolytics, glutamine release inhibition, N-methyl-D-aspartate receptor antagonism, opioid antagonism, calcium channel blockade, free radical scavenging, membrane stabilization, intercellular adhesion molecule-1 antagonism, ganglioside administration, and growth factor administration were included. Basic research articles were selected based on progress of the therapeutic class toward clinical trials. Approval of tissue plasminogen activator indicates progress in new treatments for acute ischemic stroke. Experimental therapies with potential may become available soon. Recognizing signs and symptoms of stroke is crucial to ensure prompt administration of these agents. The time to diagnosis determines the therapeutic approach for acute ischemic stroke.
Inflammatory mechanisms in ischemic stroke: therapeutic approaches
Journal of Translational Medicine, 2009
Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies.
Ischemic stroke and neuroprotection
Annals of Medical and Health Sciences Research, 2012
It is the third leading cause of death in Western countries. [2] In Africa it accounts for 4-9% of deaths and between 6.5% and 41% of neurological admissions in hospital based studies. [3] Findings from South West Nigeria show that the incidence of stroke rises with age reaching a peak in the 8 th decade in males and 7 th decade in females. [4] Stroke is classified as being either hemorrhagic or ischemic in nature depending on the underlying pathological process responsible. Several studies have documented that the ischemic subtype accounts for the greater number of stroke cases. [5-8] An ischemic stroke occurs when a cerebral vessel occludes, obstructing blood flow to a portion of the brain. The only currently approved medical stroke therapy, tissue plasminogen activator (tPA), is a thrombolytic that targets the thrombus within the blood vessel. Neuroprotective agents, another approach to stroke treatment, have generated as much interest as thrombolytic therapies. Materials and Methods An extensive search of all materials related to the topic was made using library sources including Pubmed and Medline searches. Current research findings were also included.
2013
Abstract: The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with p...
Neuroprotection for ischemic stroke: moving past shortcomings and identifying promising directions.
The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics.
Drug Discovery Today, 2012
Stroke is the third leading cause of death with an increasing prevalence. In previous years many important achievements and new therapeutic strategies have been established. This article provides an overview on recent developments and is an update to the article of Green et al. that was published in 2004. As this article is a comprehensive review we divided it in two parts. In this Part A of our review, recent developments in acute stroke treatment and in stroke prevention are described. In Part B we will reflect on neuroprotection.