Therapeutic Benefit of Intravenous Transplantation of Mesenchymal Stem Cells After Experimental Subarachnoid Hemorrhage in Rats

Abstract

Subarachnoid hemorrhage (SAH) usually occurs when an aneurysm ruptures and bleeds into the subarachnoid space. However, no information is available regarding the therapeutic potency of transplanted mesenchymal stem cells (MSCs) for SAH. Therefore, our aim was to investigate whether MSC transplantation therapy may cause stem cell activation and improve neurologic functional recovery after induction of SAH. Female rats were divided into 2 groups of SAH plus phosphate-buffered saline (PBS; control) and SAH plus MSCs (experimental). Both control and experimental groups received PBS or injection of 3 × 10(6) male rat MSCs labeled with bromodeoxyuridine (BrdU) into the tail vein 24 hours after SAH. All animals were killed 14 days after SAH. A behavioral test (Neurological Severity Score) was performed at 1, 7, and 14 days after SAH. Immunohistochemistry was used to identify MSCs and the cells derived from MSCs in brains with SAH. Terminal deoxynucleotidyltransferase mediated dUTP-biotin nick-end labeling was used to identify apoptotic cells. Significant functional recovery (P < .05) was found in SAH animals infused with MSCs compared with other rats. Significantly more BrdU-positive cells were located in the parietal lobe of MSC-treated than in PBS-treated animals. MSCs were also seen to differentiate into glial cells (GFAP), neurons (Neu-N), and endothelial cells (vWF), thereby enhancing neuroplastic effects in the injured brain. Significantly fewer apoptotic cellswere found in insulted cerebral tissue in SAH plus MSC rats when compared with other groups. Intravenously transplanted MSCs improve functional recovery, reduce apoptosis, and enhance neuroplastic effects after SAH in animal models. This is a promising novel procedure to repair central nervous system damage after SAH, and may provide a new way to induce plasticity in the injured brain cells.