BACKGROUND:Stereotactic injection(striatum or lateral ventricle) and vascular injection(tail vein or carotid artery) are now often used in cellular therapy for cerebral infarction.Stereotactic injection can accurately deliver cells to the infarct area,but requires a stereotactic device and causes secondary trauma;vascular injection is easy and better for host neurological deficit recovery,but can cause thrombosis.OBJECTIVE:To compare the therapeutic potential of adult bone marrow-derived mesenchymal stem cells(BMSCs) transplantation by intraperitoneal versus intravenous administration to cerebral ischemic rats.DESIGN,TIME AND SETTING:A randomized controlled animal experiment was performed at the Cell Room and Pathology Laboratory,Brain Hospital Affiliated to Nanjing Medical University from November 2007 to September 2008.MATERIALS:BMSCs were derived from 20 healthy Sprague-Dawley rats aged 4-6 weeks.METHODS:Forty-five adult middle cerebral artery occlusion(MCAO) rats were randomly divided into control,intravenous and intraperitoneal injection groups,with 15 rats in each group.At 21 days after modeling,rats in the control group received 1 mL of 0.01 mol/L phosphate buffered saline via tail vein injection and each experimental rat received 4 × 106 BMSCs labeled by bromodeoxyuridine(BrdU) via intravenous or intraperitoneal injection.MAIN OUTCOME MEASURES:Angiogenin expression and survival of transplanted cells were measured by immunohistochemical staining of brain tissue in infarction hemisphere at 7,14 or 21 days after BMSC transplantation.Co-expression of BrdU/microtubule-associated protein 2 or BrdU/glial fibrillary acidic protein was observed by double-labeled immunofluorescence of cerebral cortex.Evaluation of nerve function using the neurological injury severity score and the adhesion-removal test was performed on the 1st and 21st day before and after MCAO,and at 3,7,14 or 21 days after BMSCs treatment.RESULTS:Angiogenin-positive new vessels were distributed in the bilateral striatum,hippocampus and cerebral cortex of each group of rats at each time point,most markedly in the intravenous injection group.There were significantly more BrdU-positive cells in the intravenous injection group than in the intraperitoneal injection group(P < 0.01).Co-expression of BrdU/microtubule-associated protein 2 or BrdU/glial fibrillary acidic protein were almost only seen in the intravenous group by fluorescence microscopy.After transplantation,BMSCs significantly restored nerve function in rats,particularly in the intravenous injection group.CONCLUSION:BMSCs were able to enter brain tissue via the tail vein or peritoneal injection and improve neurological function by promoting the regeneration of nerves and blood vessels in vivo,more effectively after intravenous than intraperitoneal injection. BACKGROUND: Stereotactic injection (striatum or lateral ventricle) and vascular injection (tail vein or carotid artery) are now often used in cellular therapy for cerebral infarction. Stereotactic injection can delivered deliverible cells to the infarct area, but require a stereotactic device and causes secondary trauma; vascular injection is easy and better for host neurological deficit recovery, but can cause thrombosis. OBJECTIVE: To compare the therapeutic potential of adult bone marrow-derived mesenchymal stem cells (BMSCs) transplantation by intraperitoneal versus intravenous administration to cerebral ischemic rats. , TIME AND SETTING: A randomized controlled animal experiment was performed at the Cell Room and Pathology Laboratory, Brain Hospital Affiliated to Nanjing Medical University from November 2007 to September 2008. SPECIALS: BMSCs were derived from 20 healthy Sprague-Dawley rats aged 4-6 weeks.METHODS: Forty-five adult middle cerebral artery occlusion (MCAO) rats were randomly divi ded into control, intravenous and intraperitoneal injection groups, with 15 rats in each group. At 21 days after modeling, rats in the control group received 1 mL of 0.01 mol / L phosphate buffered saline via tail vein injection and each experimental rat received 4 × 106 BMSCs labeled by bromodeoxyuridine (BrdU) via intravenous or intraperitoneal injection. MAIN OUTCOME MEASURES: Angiogenin expression and survival of transplanted cells were measured by immunohistochemical staining of brain tissue in infarction hemisphere at 7, 14 or 21 days after BMSC transplantation. Co-expression of BrdU / microtubule-associated protein 2 or BrdU / glial fibrillary acidic protein was observed by double-labeled immunofluorescence of cerebral cortex. Evaluation of nerve function using the neurological injury severity score and the adhesion-removal test was performed on the 1st and 21st day before and after MCAO, and at 3, 7, 14 or 21 days after BMSCs treatment .RESULTS: Angiogenin-positive new vessels were distributed in the bilateral striatum, hippocampus and cerebral cortex of each group of rats at each time point, most markedly in the intravenous injection group. There were significantly more BrdU-positive cells in the intravenous injection group than in the intraperitoneal injection group (P <0.01) .Co-expression of BrdU / microtubule-associated protein 2 or BrdU / glial fibrillary acidic protein were almost only seen in the intravenous group by fluorescence microscopy. After transplantation, BMSCs significantly restored nerve function in rats, particularly in the intravenous injection group. CONCLUSION : BMSCs were able to enter brain tissue via the tail vein or peritoneal injection and improve neurological function by promoting the regeneration of nerves and blood vessels in vivo, more effectively after intravenous than intraperitoneal injection.