title: Therapeutic benefit of intravenous transplantation of mesenchymal stem cells after experimental subarachnoid hemorrhage in rats.
abstract: 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 × 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.
  
  
  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.
authors.affiliation: Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. khalili59@hotmail.com
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Khalili
authors.forename: Morteza
authors.initials: M
authors.lastname: Anvari
authors.forename: Sayyed H
authors.initials: SH
authors.lastname: Hekmati-Moghadam
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sadeghian-Nodoushan
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Fesahat
authors.forename: Sayyed M
authors.initials: SM
authors.lastname: Miresmaeili
mesh_terms: D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007262:Infusions, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D055495:Neurogenesis; D009457:Neuroglia / Q000473:pathology; D009460:Neurologic Examination; D009473:Neuronal Plasticity; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013345:Subarachnoid Hemorrhage / Q000473:pathology / Q000503:physiopathology / Q000523:psychology / Q000601:surgery*; D013997:Time Factors