Ischemic stroke pathophysiology

Furlan A, Higashida R. Intra-arterial thrombolysis in acute ischemic Stroke. In Mohr JP, Choi DW, Grotta JC, et al., eds. Stroke Pathophysiology, Diagnosis, and Management. 4th ed. Philadelphia, PA Churchill Livingstone 2004 p. 943-951. 

The pathophysiology of hemorrhagic stroke is not as well studied as that of ischemic stroke however, it is a more complex process than previously thought. Much of the process is related to the presence of blood in the brain tissue and/or surrounding... 

Danysz W, Parsons CG, Mobius HJ, et al (2000) Neuroprotective and symptomatological action of memantine relevant for Alzheimer s disease—an unified glutamatergic hypothesis on the mechanism of action. Neurotox Res 2 85-97 Davis SM, Lees KR, Albers GW, et al (2000) Selfotel in acute ischemic stroke possible neurotoxic effects of an NMDA antagonist. Stroke 31 347-354 DeKeyser J (1991) Excitotoxic mechanisms may be involved in the pathophysiology of tardive dyskinesia. Clin Neuropharmacol 14 562-565 Del Dotto P, Pavese N, Gambaccini G, et al (2001) Intravenous amantadine improves levodopa-induced dyskinesias an acute double-blind placebo-controlled study. Mov Disord 16 515-520... 

Many individuals with LA also harbor lacunar and/or cortical infarcts. Presence of LA serves as an intermediate surrogate both for ischemic stroke and intracerebral hemorrhage as they all share similar risk factors and similar pathophysiological mechanisms (Inzitari 2003). LA is widely found in dementing illnesses, such as Alzheimer s disease, vascular dementia, and cerebral autosomal dominant arteri-opathy with subcortical infarcts and leukoencepha-lopathy (CADASIL). Failure of blood supply in the... 

Nevertheless, the possibility of combining hypothermia with other types of neuroprotection or thrombolysis is intriguing, and certainly deserves future study. However, if this treatment is ever to impact clinical practice, it is essential that appropriate preclinical studies be conducted. In particular, the rigorous evaluation of these combinations in a variety of ischemic models that most closely simulate the pathophysiology of acute ischemic stroke, is needed. Only after such extensive testing should the possibility of combination therapy be subsequently evaluated in randomized clinical trials. 

Brott T. and Hacke W. (1998) General treatment of acute ischemic stroke. In Cerebrovascular Disease Pathophysiology, Diagnosis and Management (Ginsberg M. D. and Bogousslavsky J., eds.), Blackwell Science, Malden, pp. 1864— 1878. 

Knowledge of cerebral blood flow regulation, and the relationship between cerebral blood flow and cerebral metabolism, has had a major influence on the understanding of the pathophysiology of impaired perfusion reserve and acute ischemic stroke (Frackowiak 1986 Marchal et al. 1996 Baron 2001 Rutgers et al. 2004). 

There are limitations to the information on cerebrovascular pathophysiology in vivo that can be provided by CT and conventional MRI. Specifically, these include lack of sensitivity for acute ischemic stroke, difficulty in determining infarct age, lack of demonstration of the ischemic penumbra and low sensitivity and specificity for primary intracerebral hemorrhage in the case of MRI. New imaging techniques address some of these deficiencies and thereby impact on the management of patients with acute stroke. 

The less-striking benefit from thrombolysis indicated by the systematic reviews compared with that seen in the NINDS trial may result from methodological differences between trials. These include the fact that many of the earlier trials randomized patients up to six hours from stroke onset, and the likely pathophysiological variability in the patients studied. Further, in the NINDS trial, only carefully selected patients were included and these strict inclusion and exclusion criteria have made these trial results difficult to generalize to clinical practice. One study (Jorgensen et al. 1999) showed that only 5% of patients admitted to hospital in Denmark with ischemic stroke would fulfil fhe enfry criferia for this trial and that only 45% would be eligible for thrombolysis even when the time limit was ignored. 

W. Pulsinelli, Pathophysiology of Acute Ischemic Stroke, The Lancet 339 (1992) 533-537. 

Epoprostenol has also been used in patients with ischemic stroke. However, the pathophysiological involvement of endogenous prostaglandins in ischemic brain damage is not clear, and no studies showing significant, sustained therapeutic benefits with epoprostenol have been reported (321,322). 

Ischemic Stroke Basic Pathophysiology and Neuroprotective Strategies... 

Phillips, S.J. (1994) Pathophysiology and management of hypertension in acute ischemic stroke. 

Protectins (PDl) or Neuroprotectin Dl (NPDl) have been identified in the brain and other CNS model systans, and were first reported in 2003 (Hong et al. 2003). In other disease models not related to the brain, PDl has been found to have both antiinflammatory and protective properties in a wide range of pathophysiological models including ischemic stroke, obesity-insulin resistance and peritonitis amongst others... 

Sildenafil was the first oral treatment for ED and is the most extensively evaluated (35). Overall success rates in patients with cardiovascular disease of 80% or greater have been recorded with no evidence of tolerance, Patients with diabetes with or without additional risk factors, with their more complex, and extensive pathophysiology, have an average success rate of 60%. In randomized trials to date, open-label or outpatient monitoring studies the use of sildenafil is not associated with any excess risk of myocardial infarction, stroke, or mortality (38-40), In patients with stable angina pectoris there is no evidence of an ischemic effect due to coronary steal, and in one large, double-blind, placebo-controlled, exercise study sildenafil 100 mg increased exercise time and diminished ischemia (41), A study of the hemodynamic effects in men with severe CAD identified no adverse cardiovascular effects and a potentially beneficial effect on coronary blood flow reserve (42), Studies in patients with and without diabetes have demonstrated improved endothelial function acutely and after long-term oral dose administration, which may have implications beyond... 

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