Our results Crizotinib in dicate that estradiol treatment reduces the build up of gliotic tissue triggered by pMCAO. Moreover, estradiol treatment reversed the down regulation of the PI3K Akt GSK3 B catenin pathway induced by pMCAO in the cortex, and to a lesser extent, in the ipsilateral hippocampus. Finally, pMCAO had no effect on the acti vation status of SAPK JNK in both the cerebral cortex and hippocampus, as reflected by its phosphorylation, although post pMCAO estradiol treatment decreases SAPK JNK phosphorylation in both these areas, only sig nificantly in the hippocampus. Materials and methods Animals Experiments were performed on adult male Wistar rats Inhibitors,Modulators,Libraries obtained from the vivarium at the CBM SO. Animals were housed in a room with controlled temperature and Inhibitors,Modulators,Libraries relative humidity on an alter nating 12 12 h light dark cycle, and they were given ad libitum access to food and water.

Animal care Inhibitors,Modulators,Libraries protocols conformed Inhibitors,Modulators,Libraries to the appropriate Inhibitors,Modulators,Libraries national legislations and the guidelines of the Council of European Communities. Induction of focal cerebral ischemia Permanent focal cerebral ischemia was induced by occluding the middle cerebral artery using the previously described intraluminal suture method, with minor modifications. Rats were anesthetized with an intraperi toneal injection of a mixture of medetomidine and ketamine, accompanied by a sub cutaneous injection of atropine. The right common carotid artery was exposed and dis sected, and the right external carotid artery and right internal carotid artery were isolated.

The first artery branches of the ECA and the pterygopalatine artery were electro cauterized using a High Temperature Cautery Power Handle. To occlude the origins of the MCA, a 4 0 mono filament Dafilon nylon suture, the tip of which was rounded by heating found and that was coated with poly L lysine, was introduced into the ECA lumen and advanced into the ICA lumen until it met mild resistance, approximately 2. 2 cm beyond the CCA bifurcation. The suture was secured with a ligature and was maintained in place until sacrifice. Sham operated rats were subjected to identical surgical procedures but no suture was inserted. Neurological deficit score The neurological deficit score of each rat was measured before surgery, and 6 h after pMCAO induction, just be fore administration of the first estradiol dose, using a slightly modified version of the method described by YrjAnheikki. To determine whether ischemia was induced correctly, the assessment was performed by an individual who was blind to the experimental treatment groups.