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Title of Journal: Exp Brain Res

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Abbravation: Experimental Brain Research

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Springer-Verlag

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DOI

10.1007/bf01815555

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1432-1106

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Chronic intracerebroventricular delivery of the se

Authors: Germán Torregrosa Fernando J PérezAsensio María C Burguete María CastellóRuiz Juan B Salom Enrique Alborch
Publish Date: 2006/07/28
Volume: 176, Issue: 2, Pages: 248-259
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Abstract

Phospholipase A2s PLA2s seem to be involved in the pathophysiology of ischemic brain injury but their specific role is far from being completely understood The present study was carried out to ascertain how and to what extent secretory PLA2s sPLA2s activity influences outcome after cerebral ischemia–reperfusion and to correlate this with the inflammatory response To do this we used the potent and selective sPLA2 inhibitor 12episcalaradial Male Wistar rats were separated into three groups a control group receiving intracerebroventricular vehicle and two groups receiving intracerebroventricular 0005 or 05 μg/h 12episcalaradial Every animal was subjected to middle cerebral artery MCA occlusion 90 min intraluminal thread technique under continuous monitorization of cerebrocortical perfusion CP laserDoppler flowmetry followed by reperfusion 3 days Neurological status infarct volume and myeloperoxidase MPO activity were the main end points Three days after the 90min ischemia period neurological examination did not reveal significant differences between the three groups of rats Control rats showed a mean infarct volume of 1459 ± 247 mm3 21 ± 41 of the ipsilateral hemisphere volume while mean infarct volume in rats treated with 0005 or 05 μg/h 12episcalaradial increased to 1648 ± 868 mm3 220 ± 109 and 2115 ± 122 mm3 28 ± 3 P  005 respectively Treatment with the highest dose of 12episcalaradial 05 μg/h increased MPO activity in the ipsilateral hemisphere by about 140 from 059 ± 059 to 142 ± 103 units of activity/g of tissue in comparison with the control ischemic hemisphere P  005 Overall our results point to a positive rather than a negative influence of sPLA2 activity during ischemia This along with its inability to decrease the inflammatory response does not allow to propose the use of 12episcalardial as a potential drug for stroke therapyThe authors thank Ms María del Carmen Tirados and María del Carmen Máñez for technical assistance The present work was partially supported by a grant from Ministerio de Ciencia y Tecnología SAF980033 Fernando J PérezAsensio is supported by Centro de Investigación de Enfermedades Neurológicas CIEN Ministerio de Sanidad y Consumo C03/06 María C Burguete is supported by Ministerio de Ciencia y Tecnología SAF20010398 María CastellóRuiz is supported by Fondo de Investigación Sanitaria FIS PI030323 Ministerio de Sanidad y Consumo

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