title: Therapeutic effect of mesenchymal stem cells in rats with intracerebral hemorrhage: reduced apoptosis and enhanced neuroprotection.
abstract: Stem cell transplantation has been used to improve neural function in intracerebral hemorrhage (ICH). However, reports on bone marrow-derived mesenchymal stem cell (MSC) transplantation in ICH are limited. We aimed to explore the therapeutic effect and related mechanisms by transplantation of MSCs in rats with ICH. An experimental rat ICH model was established by intrastriatal administration of collagenase. The rats were randomly divided to receive either rat MSCs or PBS solution intravenously. In addition, behavioral tests using the modified neurological severity score (mNSS) were performed following ICH. Immunohistochemistry was performed to detect the Brdu-labeled MSCs and the protein expression of caspase 2, NF200 and GFAP in neural tissues. Western blotting and ELISA were performed to measure the protein expression of Akt and bcl-2 or the protein content of G-CSF and BDNF. The MSC-transplanted group demonstrated better neural function on the mNSS test following ICH compared with the control group (P<0.05). The MSC-transplanted group also showed reduced hemorrhage volume at 24 and 72 h following ICH. In the perihematomal regions of rat brain with ICH, a substantial number of Brdu-labeled MSCs were observed, and a high protein expression of caspase 3, NF200 and GFAP was found in the MSC-transplanted group. The protein content of Akt, Bcl-2, G-CSF and BDNF were all elevated by MSC transplantation. Intravenously transplanted MSCs are capable of improving functional recovery and restoring neurological deficits in experimental ICH. The mechanisms are associated with enhanced survival and differentiation of neural cells, and increased expression of anti-apoptotic proteins and trophic factors.
authors: The First Department of Neurology, Dalian Central Hospital, Dalian, Liaoning 116033, PR China. wangsupingzhuren@sina.com
authors: Su-Ping
authors: SP
authors: Wang
authors: Zi-Han
authors: ZH
authors: Wang
authors: Dao-Yong
authors: DY
authors: Peng
authors: Shu-Min
authors: SM
authors: Li
authors: Hong
authors: H
authors: Wang
authors: Xiao-Hong
authors: XH
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053143:Caspase 2 / Q000378:metabolism; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000628:therapy*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C051774:neurofilament protein H; D016179:Granulocyte Colony-Stimulating Factor; D051057:Proto-Oncogene Proteins c-akt; D053143:Caspase 2