ABSTRACT
Focal cerebral ischemia [st, oke] is a leading cause of death and disability among adult population. Many pathological events including inflammation and oxidative stress during the acute period contribute to the secondary neuronal death. Peroxisome prohferator-activated receptors [PPARs] are ligand-activated transcription factors known to upstream to many inflammatory and antioxidant genes. The present study was carried out to evaluate the physiological role of PPAR-gamma and possible neuroprotective effects of its agonist, rosiglitazone, in experimentally induced focal cerebral ischemia in rats. The current study was conducted on 30 male albino rats [180-220 gm], they were divided into 3 groups: Group 1: included 10 normal healthy control rats that were sham operated. Group 2: included 10 rats that were subjected to middle cerebral artery occlusion [MCAO] induced focal cerebral ischemia for 2 h followed by reperfusion for 22 h. Group 3: included 10 rats that were pretreated with rosiglitazone 3mg/kg body weight orally for 7 days followed by MCAO induced focal cerebral ischemia. The following parameters were assessed in all rats of the studied groups: Serum levels of both tumor necrosis-alpha [TNF-alpha] and interleukin-6 [IL-6] and cerebral cortex tissue levels of glutathione reductase [GR], reduced glutathi one [GSH] and glutathi one peroxidase [GPx] The present study revealed that the induced focal cerebral ischemia in rats of group2 was associated with a statistical sign ifi cant increase in serum levels of both TNF-alpha and IL-6 as compared to normal controls. Pretreatment of rats with rosiglitazone in group3 resulted in a statistical significant reduction of the TNF-alpha and IL-6 levels as compared to group2 [This reflects that the ischemic neuronal injury is associated with massive inflammatory processes that lead to brain damage]. And treatment with rosiglitazone could have an anti-inflammatory neuroprotective role. Considering the brain tissue levels of GR, GSH and GPx, which are tissue oxidant defense mechanisms, the present study showed that focal cerebral ischemia in rats of group2 led to a statistical signfi cant reduction in their levels as compared to control group indicating that cerebral ischemia and reperfusion are responsible for oxidative stress by generation of free radicals which culminate to serious damaging effect and overproduction of free radicals takes the upper hand and predominates the detoxication and scavenging capacity of cellular antioxidant enzymes. Treatment of rats with rosiglitazone before induction of focal cerebral ischemia led to a statistical significant increase in the brain tissue levels of defense antioxidant enzymes as GR and GPx as well as GSH assuming its potential neuroprotective role which could be due to its ability to increase the natural defense mechanisms in case of ischemic oxidative stress. PPAR-gamma agonist [rosiglitzone] could be the drug of use in stroke therapy due to its potential to influence multiple molecular mechanisms by its ability to minimize both the inflammation and oxidative stress and at the same time promotes the antioxidant defense mechanisms and protein chaperones