INSULIN-LIKE GROWTH FACTOR-I DECREASES APOPTOTIC CELL DEATH, BUT NOT PROAPOPTOTIC PROTEIN EXPRESSION IN A TRANSIENT FOREBRAIN ISCHEMIA-REPERFUSION MODEL IN THE RAT

Abstract

Objective: Cerebral ischemia results in bothnecrotic and apoptotic cell death. It has beensuggested that approaches directed at disruptingthe apoptotic process and expression ofproapoptotic proteins might be beneficial forpreserving functional neuronal tissue after anischemic insult. The aim was to evaluate thepresence of apoptotic cell death and the patternof expression of proapoptotic protein (bax) in atransient forebrain cerebral ischemia model andto observe the potential benefits of aneurotrophic factor IGF-I on these parameters.Methods: Female/male Wistar rats weighing200-240g were subjected to transient forebrainischemia by bilateral carotid artery occlusioncombined with systemic hypotension for 10minutes. Three reperfusion periods wereperformed as 1h, 24h and 7 days. Theexperiment was then conducted in two arms: ingroup I (n=6 for each reperfusion group),intracisternal injection of vehicle or 10 pg/rat ofIGF-I was performed at all reperfusion periods,and these rats were evaluated for the presenceof apoptosis and bax protein expression. Group II(n=4 for each reperfusion group) was evaluatedfor protein oxidation at the three reperfusionperiods.Results: Apoptosis was significantly higher(p<0.01) in the vehicle group compared to thesham group, and IGF-I treatment resulted in asignificant decrease of apoptosis compared tothe vehicle treated group at 24 hour reperfusion.Moreover, a peak in apoptotic cell death at 24hour reperfusion was observed, howeverremaining just short of significance (p = 0.0730).No difference in bax protein expression andprotein oxidation could be demonstratedbetween reperfusion periods and after IGF-I use.Conclusion: 10pg/rat of IGF-I produces asignificant suppression in apoptotic cell death at24 hours reperfusion following transient forebrainischemia.Key Words: IGF-I, Apoptosis, Rat, Forebrainischemia.