Influence of Bone Marrow Mesenchymal Stem Cell Transplantation on growth-associated protein-43 Expression in Rats with Cerebral Infarction

BACKGROUND: Growth-associated protein-43 is the primary substance for constructing plasticity of central nervous system, which is recognized as the first molecular marker for studying growth and repairing injury of nerves. OBJECTIVE: To explore the expression of growth-associated protein-43 in rats with focal cerebral ischemia following bone marrow mesenchymal stem cells (MSCs) transplantation. DEISNG, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of Department of Neurology, Renmin Hospital of Wuhan University and Doctoral Scientific Research Work Station of C-BONS Pharmacy, Hubei, China, from March 2006 to October 2007. MATERIALS: Sixty adult Sprague Dawley rats, with clean grade, irrespective of genders, weighing (180±20) g, were randomly divided into the model, sham operated, and MSCs transplantation groups, with 20 animals in each group. METHODS: Additional 4 Sprague Dawley rats, aged 2 months, were selected to isolate and culture MSCs, which was labeled with 5-Bromo-2, -deoxyuridine (BrdU). In the sham operated group, the right internal carotids were deligated after anaesthesia. The remained rats were prepared for models of right middle cerebral artery ischemia. At 24 hours after model preparation, 20 μL culture solution containing 5×10^5 /L MSCs was injected into the left lateral ventricle of rats in the MSCs group, the same volume of phosphate buffer saline was injected in the model group. MAIN OUTCOME MEASURES: The rats were sacrificed prior to and at days 7, 14, and 21 after transplantation. The expression of growth associated protein-43 at the infarcted areas, the survival and migration of transplanted cells were examined by immunohistochemistry, at the same time, neurological deficit scores were recorded. RESULTS: The transplanted MSCs migrated from the left lateral ventricle to the infracted areas. Seven days after transplantation, the expression of BrdU-positive cells was found, reached a peak at day 14, and gradually decreased, until disappeared at 28 days after transplantation. Results of immunohistochemistry image analysis showed that immunological activity of growth associated protein-43 around the infarcted area of the MSCs group was obviously greater than that of the model group at days 7 and 14 after transplantation (P＜0.05). There was no neurological deficit in the sham operated group. Moreover, with time prolonged, the neurological deficit scores gradually decreased in the model and MSCs groups, which were significantly lower in the MSCs group compared to the model group at day 14 after transplantation (P＜0.05). CONCLUSION: MSCs transplantation up-regulates the expression of growth associated protein-43 around the infarcted area, which is consistent with the recovery of neurological function.