Journal
NEUROSCIENCE
Volume 141, Issue 2, Pages 687-695Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2006.04.054
Keywords
astrocyte; gap junction protein; synaptophysin; functional recovery; ischemia
Categories
Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS042345, P01NS023393, R01NS045041] Funding Source: NIH RePORTER
- NINDS NIH HHS [P01 NS23393, P01 NS042345, R01 NS045041, R01 NS45041] Funding Source: Medline
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Bone morphogenetic proteins play a key role in astrocytic differentiation. Astrocytes express the gap junctional protein connexin-43, which permits exchange of small molecules in brain and enhances synaptic efficacy. Bone marrow stromal cells produce soluble factors including bone morphogenetic protein 2 and bone morphogenetic protein 4 (bone morphogenetic protein 2/4) in ischemic brain. Here, we tested whether intra-carotid infusion of bono marrow stromal cells promotes synaptophysin expression and neurological functional recovery after stroke in rats. Adult male Wistar rats were subjected to 2 h of right middle cerebral artery occlusion. Rats were treated with or without bone marrow stromal cells at 24 h after middle cerebral artery occlusion via intraarterial injection (n=8/group). A battery of functional tests was performed. Immunostaining of 5-bromo-2-deoxyuridine, Ki67, bone morphogenetic protein 2/4, connexin-43, synaptophysin, glial fibrillary acidic protein, neuronal nuclear antigen, and double staining of 5-bromo-2-deoxyuridine/glial fibrillary acidic protein, 5-bromo-2-deoxyuricline/neuronaI nuclear antigen, glial fibrillary acidic protein/bone morphogenetic protein 2/4 and glial fibrillary acidic protein/connexin-43 were employed. Rats treated with bone marrow stromal cells significantly (P < 0.05) improved functional recovery compared with the controls. 5-Bromo-2-deoxyuridine and Ki67 positive cells in the ipsilateral subventricular zone were significantly (P < 0.05) increased in bone marrow stromal cell treatment group compared with the controls, respectively. Administration of bone marrow stromal cells significantly (P < 0.05) promoted the proliferating cell astrocytic differentiation, and increased bone morphogenetic protein 2/4, connexin-43 and synaptophysin expression in the ischemic boundary zone compared with the contrals, respectively. Bone morphogenetic protein 2/4 expression correlated with the expression of connexin-43 (r=0.84, P < 0.05) and connexin-43 expression correlated with the expression of synaptophysin (r=0.73, P < 0.05) in the ischernic boundary zone, respectively. Administration of bone marrow stromal cells via an intra-carotid route increases endogenous brain bone morphogenetic protein 2/4 and connexin-43 expression in astrocytes and promotes synaptophysin expression, which may benefit functional recovery after stroke in rats. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.
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