الفهرس 
INTRODUCTION AND AIM OF THE WORKOnly 14 pages are availabe for public view
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Abstract
This study aimed to investigate the neuroprotective role of a short acting SSRI, dapoxetine, in global cerebral I/R injury. It also elaborates its effect in the improvement of neurobehavioral outcomes after I/R injury.
Induction of global cerebral ischemia was achieved via BCCAO for 30 minutes in adult male Wistar rats followed by 24 h reperfusion. Rats were subjected to BCCAO or sham operation. They were divided into five groups; sham operated rats, sham DAP pretreated rats, untreated I/R rats, I/R + DAP 30 mg/kg pretreated rats and I/R + DAP 60 mg/kg pretreated rats. DAP was injected I.P one hour before surgery.
After one day reperfusion, all rats were subjected to behavioral tests to assess neurobehavioral outcomes after ischemia. These tests include open field test, closed field test, beam walking test and adhesive removal test. After evaluating the performance of rats in these tests, they were scarified and brain tissues were collected for :
Measurement of oxidative stress markers ( lipid peroxidation (MDA level), catalase activity and reduced GSH level ) through biochemical tests.
Evaluation of cerebral protein expression of various inflammatory and apoptotic markers (TNF-α, TGF-β R2, iNOS and caspase-3) through Western blot analysis.
Measurement of cerebral infarct volume using TTC stain.
Assessment of histopathological changes in cerebral cortex and hippocampal region of brain.
The results of our hypothesis could be summarized as the following :
Cerebral ischemia induced by 30 minutes carotid arteries occlusion followed by 24 h reperfusion exacerbated the neurobehavioral functions. Poor motor, exploratory and somatosensory outcomes were observed in untreated I/R group. Large cerebral infarct volume and histopathological damage were also observed in brain tissues of these animals. These changes were correlated with elevated oxidative stress and reduced anti-oxidant capacity as shown by increased MDA level and reduced catalase activity and GSH level. Moreover, protein expression of TNF-α, TGF-β R2, iNOS and caspase-3 were highly elevated in these animals compared to sham operated rats.
Compared to untreated I/R rats, pretreatment with DAP (30 mg/kg and 60 mg/kg) improved the neurobehavioral outcomes, as well as reduced cerebral infarct volume. It also improved the histopathological features in cortex and hippocampus brain tissues. Besides, DAP exerted an anti-oxidant role after ischemia as it reduced MDA level and increased reduced GSH level. It also attenuated apoptosis and neuroinflammation as shown by reduced protein expression of TNF-α, TGF-β R2, iNOS and caspase-3.
The small dose of DAP (30 mg/kg) showed higher improvement in neurobehavioral performance and histopathological outcomes with less inhibition of cerebral protein expression of apoptotic and inflammatory mediators compared to the higher dose (60 mg/kg).
In conclusion, DAP ameliorated I/R induced cerebral damage. It improved neurobehavioral outcomes, reduced cerebral infarct volume and attenuated histopathological damage through its anti-apoptotic, anti-inflammatory and anti-oxidant activities.