ABSTRACT
Stroke is most important cause of death and disability in adults. The hippocampal CA1 and sub-ventricular zone neurons are vulnerable to ischemia that can impair memory and learning functions. Although neurogenesis normally occurs in the dentate gyrus [DG] of the hippocampus and sub-ventricular zone [SVZ] following brain damage, this response is unable to compensate for severely damaged areas. This study aims to assess both neurogenesis and the neuroprotective effects of transforming growth factor-alpha [TGF-alpha] on the hippocampus and SVZ following ischemia-reperfusion. In this experimental study, a total of 48 male Wistar rats were divided into the following groups: surgical [n=12], phosphate buffered saline [PBS] treated vehicle shams [n=12], ischemia [n=12] and treatment [n=12] groups. Ischemia was induced by common carotid occlusion for 30 minutes followed by reperfusion, and TGF-alpha was then injected into the right lateral ventricle. Spatial memory was assessed using Morris water maze [MWM]. Nestin and Bcl-2 family protein expressions were studied by immunohistochemistry [IHC] and Western blot methods, respectively. Finally, data were analyzed using Statistical Package for the Social Sciences [SPSS, SPSS Inc., Chicago, USA] version 16 and one-way analysis of variance [ANOVA]. TGF-alpha injection significantly increased nestin expression in both the hippocampal DG and SVZ areas. TGF-alpha treatment caused a significant decrease in Bax expression and an increase in Bcl-2 anti-apoptotic protein expression in the hippocampus. Our results showed a significant increase in the number of pyramidal neurons. Memory also improved significantly following TGF-alpha treatment. Our findings proved that TGF-alpha reduced ischemic injury and played a neuroprotective role in the pathogenesis of ischemic injury
Subject(s)
Animals, Laboratory , Memory Disorders , Memory , Neurogenesis , Reperfusion Injury , Hippocampus , Rats, WistarABSTRACT
Several studies have shown that, although transplantation of neural stem cells into the contusion model of spinal cord injury [SCI] promotes locomotor function and improves functional recovery, it induces a painful response, Allodynia. Different studies indicate that bone marrow stromal cells [BMSCs] and Schwann cells [SCs] can improve locomotor recovery when transplanted into the injured rat spinal cord. Since these cells are commonly used in cell therapy, we investigated whether co-transplantation of these cells leads to the development of Allodynia. In this experimental research, the contusion model of SCI was induced by laminectomy at the T8-T9 level of the spinal cord in adult female wistar rats [n=40] weighting [250-300g] using the New York University Device. BMSCs and SCs were cultured and prelabeled with 5-bromo-2-deoxyuridine [BrdU] and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiI] respectively. The rats were divided into five groups of 8 including: a control group [laminectomy only], three experimental groups [BMSC, SC and Co-transplant] and a sham group. The experimental groups received BMSCs, SCs, and BMSCs and SCs respectively by intraspinal injection 7 days after injury and the sham group received serum only. Locomotion was assessed using Basso, Beattie and Bresnahan [BBB] test and Allodynia by the withdrawal threshold test using Von Frey Filaments at 1, 7, 14, 21, 28, 35, 42, 49 and 56 days after SCI. The statistical comparisons between groups were carried out by using repeated measures analysis of variances [ANOVA]. Significant differences were observed in BBB scores in the Co- transplant group compared to the BMSC and SC groups [p< 0.05]. There were also significant differences in the withdrawal threshold means between animals in the sham group and the BMSC, SC and the Co-transplant groups [p<0.05].BBB scores and withdrawal threshold means showed that co-transplation improved functioning but greater Allodynia compared to the other experimental groups. The present study has shown that, although transplantation of BMSCs, SCs and a combination of these cells into the injured rat spinal cord can improve functional recovery, it leads to the development of mechanical Allodynia. This finding indicates that strategies to reduce Allodynia in cell transplantation studies are required