Isquemia cerebral focal transitoria en rata: caracterización y utilidad del modelo de la sutura intraluminal en el estudio de estrategias neuroprotectoras.

by Pérez Asensio, Fernando Jesús

Abstract (Summary)
ABSTRACT Ictus are neurological disorders originated by acute cerebral isquemia. Ictus incidence in Spain is of approximately 200 cases for every 100.000 inhabitants, which it places as the second reason of mortality. With the exception of the application of trombolitic therapy, at the moment it does not exist in clinic any other effective treatment for the ictus. The generic aim of the present work is to evaluate the neuroprotective potential of certain substances capable of interfering on three fisiopathological mechanisms implied in the cerebral damage produced by the isquemia-reperfusión: nitric oxide, oxidative stress and inflammation. Previously, the cerebral ischemia induced by transient occlusion of the medial cerebral artery using the intraluminal nylon thread model was characterized. The results confirm the isquemia-reperfusion induced expression of the inducible nitric oxide sintase (iNOS) in the brain, which mediates the ATP fall and the liberation of glutamate. The neuroprotective effect of the iNOS inhibitor, 1400W, confirms that nitric oxide produced by iNOS contributes to the damage produced by the cerebral isquemia and also the possible utility of L-arginina and L-glutamate determination in plasma as scoreboards of the ischemic damage. The administration of a single dose of ebselen, a seleno-organic compound mimetic of the antioxidant glutathione peroxidase enzyme, whose enzymatic activity is inhibited during the isquemia and reperfusion, does not reduce the size of the infracted tissue after severe ischemia in spite of a light preservation of the intraischemic cerebrocortical perfusion. These results do not agree with those obtained in previous studies using less severe ischemic insults and more short survival times. The intracerebroventricular administration of 12-epi-scalaradial, an inhibitor of the secretory phospholipase A2 (sPLA2) activity -supposed involved in the development of the inflammatory response after ischemia and reperfusion-, increased the size of the resultant lesion as well as the leukocytic infiltration in the affected tissue. These results suggest that at least some isoforms of sPLA2 might have a neuroprotective effect in the cerebral ischemia and therefore, its inhibition would be deleterious for the cerebral ischemic tissue.
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Bibliographical Information:

Advisor:Alborch Domínguez, Enrique; Torregrosa Bernabé, Germán

School:Universitat de València

School Location:Spain

Source Type:Master's Thesis



Date of Publication:09/21/2005

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