Studies on the Molecular Mechanism of Glutamate Transporters in Glutamate Homeostasis During Cerebral Ischemia/Reperfusion Injury

Abstract

Cerebral ischemia is one of the major cerebrovascular disorders which rank third in terms of death and disability among all the disorders encountered by human beings world over. Despite this tremendous burden we have not enough therapies for its cure. A large number of drugs found to be effective in preclinical studies failed in clinical trials. Among the various reasons cited for their failure, inadequate knowledge of pathophysiological events and inappropriate targets characterization were considered to be the major reasons. Therefore it may be beneficial if some therapeutic targets are identified and validated before proceeding towards drug development. In this work, sincere efforts has been made to validate such a target, which have the qualities of a potential therapeutic target for the treatment of ischemic disorders like stroke. This work has been divided into seven different chapters. Chapter one: contains the brief introduction about the diseases and glutamate transporter proteins and their role in cerebral stroke. Chapter two: contains aims and objectives as well as plan of work for the proposed research work of this study. Chapter three: contains the detailed literature survey about the stroke epidemics, types, causes, models and mechanism of ischemic pathophysiology. Further, the role of non neuronal cells specially astrocytes has been documented in this chapter. Besides this, detailed information about glutamate transporter proteins as well as its interaction with different aspects of ischemic pathophysiology has been given in this chapter. Chapter four: contains detailed list of materials and methodology, which were used to fulfill the objectives of this study. Chapter five: deals with the detailed results and discussion of the research work. For the convenience of the readers this chapter has been further subdivided into three sections Section one contains the preliminary studies covering general expression profile of GLT-1 expression. Section two contains the GLT-1 mediated neuroprotective effect of ceftriaxone and underlying mechanism of its regulation. Section three contains the effect of rosiglitazone on neuroprotection in MCAO model of cerebral stroke. Chapter six: contains the summary, conclusions and future prospects of the work. Chapter seven: give information about sources of literature and references.