Efeito neuroprotetor do pré-condicionamento por estresse de contensão sobre a lesão induzida por breve mudança subcrítica isquêmica : papel dos receptores A1 da adenosina

• Ano de defesa: 2009
• Autor(a) principal: Fontenele Filho, Ailton Teles
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Ataque Isquêmico Transitório; Adenosina; Cafeína
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/2181

Stroke,as disabling disease and as third cause death in developed countries, is characterized for the interruption of cerebral blood flow capable to cause alteration on brain functions. It is well established that the activation of A1 adenosine receptor confers neuroprotection against acute noxious brains stimuli. The aim of this study was to investigate the effects of preconditionnement by restraint stress on rats subjected to transient cerebral ischemia (TCI) and the participation of A1 receptor in this process. Firstly, Wistar male rats weighing 200-240g were exposed to immobilisation stress for 2 hours followed to TCI by occlusion of both carotid arteries for 30 minutes. Group of animals were pretreated with A1 receptor antagonist DPCPX (0,1mg/kg or 1 mg/kg. i.p.) before immobilisation stress. Retal temperature was monitored and 37°C were maintened during cirurgical procedure using a heating light. Infarct size was determined by TTC staining 24h after TCI and the behavioral tests were performed after 72 hours. Open field test were used to assess locomotor activity, Y-maze test for working memory and passive avoidance test to aversive short and long term memory evaluation. Our results showed that TCI caused damage on brain tissue (sham operated= 10.36 ± 0.75%; ISC= 18.52 ± 2.62%), decreased the vertical exploratory behavior (number of events: sham= 5.00 ± 1.23; ISC= 1.50 ± 0.72) and deficit on long term aversive memory (sham= 271.2 ± 17.61s; ISC= 108.4 ± 67.64s). No differences were found on the crossing behavior (sham= 15.71 ± 2.02; ISC= 11.00 ± 2.13), working memory (sham= 70.16 ± 5.77; ISC= 71.37 ± 7.94) neither short term memory (sham= 145.9 ± 42.75; ISC= 113.1 ± 64.97). The infarct volume rates on restraint stress (RS) group were significantly less than ischemic (ISC) group (sham= 10.36 ± 0.75%; ISC= 18.52 ± 2.62%; RS= 12.59 ± 0.87%) while the number of rearing were significantly higher (sham= 5.00± 1.23; ISC= 1.50± 0.72; RS= 6.091± 1.443). On the passive avoidance test, restraint stress tend to impair the ischemic damage on the long term memory (sham= 271.2 ± 17.61s; ISC= 108.4 ± 67.64s; RS= 156.1 ± 45.81s). When treated with DPCPX (1mg/kg) the infarct size show an increase (ISC= 18.52 ± 2.62%; RS = 12.59 ± 0.87%; DPCPX= 19.95 ± 3.38%) suggesting a blockade of neuroprotection action achieved by restraint stress. DPCPX also decreased the number of rearing on the open field test (ISC= 1.50 ± 0.72; RS= 6.091± 1.443; DPCPX = 3.20 ± 0.90) and tend to reverse the improvement of long term aversive memory accessed by restraint stress (ISC= 108.4 ± 67.64s; RS= 156.1 ± 45.81s; DPCPX 1= 88.61± 38.83s). This work showed a neuroprotection of pre conditioning restraint stress against cerebral ischemia and the blockade of this action by a previously administration of DPCPX, A1 adenosine antagonist. These findings point to the involvement of the A1 adenosine receptor in the protection conferred by restraint stress by mechanisms that still need to be clarified.