Effects and mechanısms of actıon of ghrelın on learnıng and memory changes ın experımental cerebral ıschemıa reperfusıon model.

Cerebral ischemia is the third leading cause of death and first cause of morbidity worldwide. Hundreds of thousands of people suffer from cerebral ischemia reperfusion injury each year and approximately 45% of those patients cannot heel without private medical aid. Since the most striking result of cerebral ischemia reperfusion injury is learning and memory impairment, we focused on mechanisms relating cerebral ischemia reperfusion injury to hippocampal damage. Ghrelin, so-called hunger hormone, is used as a therapeutic agent in our study because of its antioxidant and memory enhancing effects.Eighty adult male Wistar rats were divided randomly into Sham (SHAM), Ghrelin (GHR), Ischemia/Reperfusion (I/R) and Ischemia/Reperfusion+Ghrelin (I/R+GHR) groups. SHAM group rats only underwent sham surgery, i.e. without any vessel occlusion, and received saline daily for three reperfusion days. GHR group rats also underwent sham surgery, additionally, they were administered ghrelin daily for three days of reperfusion. I/R group rats were exposed to global cerebral ischemia/reperfusion and given saline daily for three days of reperfusion. I/R+GHR group rats, however, both underwent global cerebral ischemia/reperfusion surgery and received ghrelin daily for three days of reperfusion. Y-Maze and Open Field tests were carried out at postischemic 24th and 48th hours. On the third reperfusion day, blood samples and brains of the animals were collected. Plasma acylated ghrelin levels, plasma unacylated ghrelin levels, total oxidant status (TOS), total antioxidant status (TAS), nitrate + nitrite levels, iNOS and nNOS expressions in the hippocampi were analysed.Y-maze and Open Field test results revealed that cerebral ischemia/reperfusion caused learning and memory impairment due to hippocampal damage. Furthermore, ghrelin administration attenuated ischemia/reperfusion induced cognitive impairment. High TOS levels of I/R group were in consistency with hippocampal damage. Plasma acylated ghrelin levels were increased in GHR group with respect to SHAM group and, I/R+GHR group acylated ghrelin levels were significantly decreased with respect to GHR and I/R groups. Unacylated ghrelin plasma levels were dramatically decreased in I/R+GHR group in reference to SHAM and I/R groups. Hippocampal nitrate+nitrite levels of GHR, I/R and I/R+GHR groups were sharply increased with respect to SHAM group. iNOS expression in the hippocampi of I/R group was markedly increased in reference to other groups. nNOS levels of GHR, I/R and I/R+GHR groups were slightly increased in reference to SHAM group.In conclusion, our study clearly showed that cerebral ischemia/reperfusion resulted in TOS increase coupled with cognitive impairment and ghrelin can be proposed as a therapeutic agent for cerebral ischemia/reperfusion injury.