Background and Purpose-We tested the hypothesis that intravenous infusion of bone marrow derived-marrow stromal cells (MSCs) enter the brain and reduce neurological functional deficits after stroke in rats. Methods-Rats (nϭ32) were subjected to 2 hours of middle cerebral artery occlusion (MCAO). Test groups consisted of MCAO alone (group 1, nϭ6); intravenous infusion of 1ϫ10 6 MSCs at 24 hours after MCAO (group 2, nϭ6); or infusion of 3ϫ106 MSCs (group 3, nϭ7). Rats in groups 1 to 3 were euthanized at 14 days after MCAO. Group 4 consisted of MCAO alone (nϭ6) and group 5, intravenous infusion of 3ϫ10 6 MSCs at 7 days after MCAO (nϭ7). Rats in groups 4 and 5 were euthanized at 35 days after MCAO. For cellular identification, MSCs were prelabeled with bromodeoxyuridine. Behavioral tests (rotarod, adhesive-removal, and modified Neurological Severity Score [NSS]) were performed before and at 1, 7, 14, 21, 28, and 35 days after MCAO. Immunohistochemistry was used to identify MSCs or cells derived from MSCs in brain and other organs. Results-Significant recovery of somatosensory behavior and Neurological Severity Score (PϽ0.05) were found in animals infused with 3ϫ10 6 MSCs at 1 day or 7 days compared with control animals. MSCs survive and are localized to the ipsilateral ischemic hemisphere, and a few cells express protein marker phenotypic neural cells. Conclusions-MSCs delivered to ischemic brain tissue through an intravenous route provide therapeutic benefit after stroke. MSCs may provide a powerful autoplastic therapy for stroke.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies.

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Background and Purpose-Human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether ischemic brain tissue extract selectively induces chemotaxis of HUCBC in vitro. Methods-Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO).Experimental groups were as follows: group 1, MCAO alone (nϭ5); group 2, 3ϫ10 6 HUCBC injected into tail vein at 24 hours after MCAO (nϭ6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (nϭ5); group 4, MCAO injected with PBS at 1 day after stroke (nϭ8); and group 5, 3ϫ10 6 HUCBC injected into tail vein at 7 days after MCAO (nϭ5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO.