Effects of FK506 on Hippocampal CA1 Cells Following Transient Global Ischemia/Reperfusion in Wistar Rat

Abstract

Transient global cerebral ischemia causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In experimental group 1, FK506 (6 mg/kg) was given as a single dose exactly at the time of reperfusion. In the second group, FK506 was administered at the beginning of reperfusion, followed by its administration intraperitoneally (IP) 6, 24, 48, and 72 hours after reperfusion. FK506 failed to show neurotrophic effects on CA1 region when applied as a single dose of 6 mg/kg. The cell number and size of the CA1 pyramidal cells were increased, also the number of cell death decreased in this region when FK506 was administrated 48 h after reperfusion. This work supports the possible use of FK506 in treatment of ischemic brain damage.

Combined Neuroprotective Action of JWH-015 and AM251 in the CA1 Hippocampal Area of Transient Global Cerebral Ischemia

“…The results showed that ischemic rats had significant higher number of TUNEL-positive cells and lower number of alive cells compared to the control. To explain, the same results were obtained with 20 min induction of ischemia by BCCAO in the works performed by Sharifi et al [20], Movassaghi et al [21] in rats and Mori et al [22] in mice. The results of TUNEL assay and Nissl staining in the ischemic rats were significantly counteracted by combined application of AM251 and JWH-015, as compared with each of the ischemia, AM251, and JWH-015 groups.…”

“…To see if the combined application of AM251 + JWH-015 could affect spatial memory, we evaluate MWM in the studying groups, and we found impairment of spatial memory in the ischemic group. To explain, pyramidal neurons of the CA1 hippocampal area are particularly sensitive to ischemia, and their apoptosis is an outcome of transient GCI [20]. Therefore, memory deficit is one of the outcomes of transient GCI [5], as in the study carried out by Movassaghi et al who found that exposure of rats to BCCAO could impair spatial memory [21].…”

Chlorogenic acid ameliorates memory loss and hippocampal cell death after transient global ischemia

“…Four to five animals of the same group were placed in the same cage. Transient global ischemia (TGI) model was performed using the bilateral common carotid occlusion (BCCO) method based on the protocol of previous studies (Hatakeyama, Matsumoto, Brengman, & Yanagihara, ; Martinez, Musumeci, Loreto, & Carnazza, ; Sharifi et al., ; Yu et al., ; Zhao, Zhang, Guo, & Zhang, ; Zheng, Liu, Wang, & Xu, ). The rats were anesthetized using intramuscular injection of 100 mg/kg bw of ketamine (PT Guardian Pharmatama, Jakarta, Indonesia).…”

Immunosuppressant FK506: Focusing on neuroprotective effects following brain and spinal cord injury

“…The effect of FK506 on neurological outcome was investigated only in the study by Zawadska and Kaminska (2005). Recently, neuroprotective effect of FK506 on CA1 neurons of hippocampus was confirmed following transient global ischemia (Sharifi et al, 2012). In comparison to brain ischemia, a higher FK506 dose was used for axonal neuroprotection in traumatic brain injury (TBI) studies.…”