Hemorrhagic Stroke and the genetic influence of Fibronectin gene Polymorphisms(SNPs)

Hemorrhagic Stroke and the Genetic Influence of Alfa-1 Antichymotrypsin Gene Polymorphism

Summary of the Proposal

There is a noted increased prevalence of hemorrhagic stroke in patients with ACT-TT genotype polymorphism . The strongest association is noted in patients who have intracranial bleeds despite normal blood pressure values . The role of proteolytic enzymes in the pathophysiology of cerebral bleeding has been suggested very recently . ACT is a protease inhibitor that regulates the activity of serine proteases such as neutrophil cathepsin G . Release of this enzyme may lead to degradation of the vascular

matrix proteins and coagulation factors . A study of association of incidence of parenchymal intracerebral hemorrhage and alfa-1 antichymotrypsin genetic polymorphism may indicate a marker for parenchymal intracerebral hemorrhagic stroke to lead to possible interventions in this disabling and fatal disease

Introduction

Most cerebrovascular diseases present as an abrupt onset of a focal neurological deficit that is referred to as a stroke . In the United States , the term stroke is generally used specifically to mean cerebral infarction . The term hemorrhagic stroke is used to indicate cerebrovascular accident due to intracerebral hemorrhage . This happens due to bleeding within the brain parenchyma , subarachnoid space , or the subdural or epidural space . The majority of the intracerebral hemorrhages are associated with hypertension however , spontaneous hemorrhage , arteriovenous malformations , and other causes are less common (Vila , N , Obach , V , Revilla , M , Oliva , R ,and Chamorro , A 2000

Aims and Objectives

Generally , within 10 s after cerebral blood flow ceases , metabolic failure of cerebral brain tissue occurs . The electroencephalogram done at that point in time would demonstrate slowing of electrical activity and the brain dysfunction would be clinically manifest . If the circulation is restored immediately , there is abrupt and complete recovery of function . If the perfusion abnormality persists for a few minutes , neuronal injury results . With restoration of flow , the recovery of function takes several minutes or hours and may be incomplete . In addition to this , pathologically , there might be a no-reflow phenomenon This means during the circulatory failure , the blood elements may sludge , and the capillary endothelium may swell . Even if the primary cause of the flow failure is corrected , the blood flow may not re-establish itself (Pawlikowska , L .et al , 2004

More prolonged period of ischemia may result in frank tissue necrosis This would initiate cerebral edema , and typically this would progress over 3 to 4 days . By far , this is the most common type of nontraumatic intracranial hemorrhage . Hypertension and cerebral myloid angiopathy cause the majority of these hemorrhages

Background and Significance

Hypertensive Intracerebral Hemorrhage : In these patients , intracerebral hemorrhage usually results from spontaneous rupture of a small penetrating artery deep in the brain . The small arteries in certain specific areas , such as , the basal ganglia , the deep cerebellum , and the pons seem more prone to hypertension-induced vascular injury . The leak may be small , or a large clot may form and compress the adjacent tissue Despite recent advances in acute stroke therapy , hemorrhagic stroke remains the leading cause of severe disability and the third leading...