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

Background 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 tr...

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Bibliographic Details
Published in:Journal of stroke and cerebrovascular diseases 2012-08, Vol.21 (6), p.445-451
Main Authors: Khalili, Mohammad Ali, PhD, Anvari, Morteza, PhD, Hekmati-Moghadam, Sayyed H., MD, Sadeghian-Nodoushan, Fatemeh, MSc, Fesahat, Farzaneh, MSc, Miresmaeili, Sayyed M., MSc
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Behavior, Animal
Brain - pathology
Brain - physiopathology
Cardiovascular
Cell Differentiation
Cell Movement
Cell Survival
Disease Models, Animal
Endothelial Cells - pathology
Female
Immunohistochemistry
In Situ Nick-End Labeling
Infusions, Intravenous
Male
mesenchymal stem cell
Mesenchymal Stem Cell Transplantation
Neurogenesis
Neuroglia - pathology
Neurologic Examination
Neurology
Neuronal Plasticity
Neurons - pathology
rat
Rats
Rats, Wistar
Recovery of Function
subarachnoid hemorrhage
Subarachnoid Hemorrhage - pathology
Subarachnoid Hemorrhage - physiopathology
Subarachnoid Hemorrhage - psychology
Subarachnoid Hemorrhage - surgery
Time Factors
transplantation
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Summary:Background 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. Methods 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 × 106 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. Results 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 cells were found in insulted cerebral tissue in SAH plus MSC rats when compared with other groups. Conclusions 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.
ISSN:1052-3057
1532-8511
DOI:10.1016/j.jstrokecerebrovasdis.2010.10.005