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P222 Most bone marrow cells (BMCs) transplanted into the ischemic  brain of adult rodents die shortly after they are grafted, similar to  the 90%-95% of the fetal cells that die after transplantation into  Parkinson s patients. We tested whether coadministration of BMCs and  Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD), an inhibitor of apoptosis,  into the ischemic boundary zone of the striatum and the cortex in rat  brain promotes BMC survival. Adult Wistar rats were subjected to  transient (2 h) middle cerebral artery occlusion (MCAo). At 1 d  after ischemia, saline (n=9, Group 1); BMCs (1x106 in 10  :l, n=8, Group 2); or BMCs with Z-VAD (50 nM/ml, n=4, Group 3) were  injected into brain. BMCs were harvested from donor adult rats injected  with bromodeoxyuridine (BrdU, as a tracer). Rats were subjected to  rotarod-motor and adhesive-removal somatosensory functional tests  before MCAo and at 1 and 7 d after MCAo. Rats in Group 3 exhibited  significant improvement (10.3±2.6 seconds, p&lt;0.05) on the  adhesive-removal test at 7 d, compared with those in Group 1  (29.3±9.4 seconds) and Group 2 (21.3±5.5 seconds), respectively.  Immunohistochemistry staining was employed to identify BrdU-BMCs, and  TUNEL staining was used to identify in situ DNA fragmentation of  apoptotic cells. Even though the infarct volume in Group 3  (29.9±9.2%) did not change significantly, compared with Group 1  (34.3±4.0%) and Group 2 (26.6±3.8%); the number of BrdU-BMCs  (88,200±7,400, ∼8.8% of 106 transplanted cells)  increased significantly (p&lt;0.05) in rats in Group 3, compared with  that in Group 2 (31,700±9,100, ∼3.2% of 106 cells) at  7 d. In the grafting areas, apoptotic cells were less clustered  ( 240 per region) and apoptotic cells were significantly  decreased (12.3±1.7/mm2 vs. 25.9±2.1/mm2 ,  ∼47%, p&lt;0.05). Our data suggest that intracerebral coadministration  of bone marrow cells and inhibitors of apoptosis enhance cellular  survival of bone marrow cells and improves neurological functional  recovery after cerebral ischemia.

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Coadministration of bone marrow cells and an inhibitor of apoptosis (Z-VAD) promotes bone marrow cell survival and neurological functional recovery after focal cerebral ischemia in adult rat