Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells
Version of Record online: 11 NOV 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 49, Issue 3, pages 407–417, February 2005
How to Cite
Li, Y., Chen, J., Zhang, C. L., Wang, L., Lu, D., Katakowski, M., Gao, Q., Shen, L. H., Zhang, J., Lu, M. and Chopp, M. (2005), Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia, 49: 407–417. doi: 10.1002/glia.20126
- Issue online: 20 DEC 2004
- Version of Record online: 11 NOV 2004
- Manuscript Accepted: 24 AUG 2004
- Manuscript Received: 14 MAY 2004
- National Institute of Neurological Disorders and Stroke (NINDS). Grant Numbers: PO1 NS23393, RO1 NS45041
- cerebral ischemia;
- bone marrow stromal cells;
- functional recovery;
The long-term (4-month) responses to treatment of stroke in the older adult rat, using rat bone marrow stromal cells (MSCs), have not been investigated. Retired breeder rats were subjected to middle cerebral artery occlusion (MCAo) alone, or injected intravenously with 3 × 106 MSCs, at 7 days after MCAo. Functional recovery was measured using an adhesive-removal patch test and a modified neurological severity score. Bromodeoxyuridine, a cell proliferation marker, was injected daily for 14 before sacrifice. Animals were sacrificed 4 months after stroke. Double immunostaining was used to identify cell proliferation and cell types for axons, astrocytes, microglia, and oligodendrocytes. MSC treatment induced significant improvement in neurological outcome after MCAo compared with control rats. MSC treatment reduced the thickness of the scar wall (P < 0.05) and reduced the numbers of microglia/macrophages within the scar wall (P < 0.01). Double staining showed increased expression of an axonal marker (GAP-43), among reactive astrocytes in the scar boundary zone and in the subventricular zone in the treated rats. Bromodeoxyuridine in cells preferentially colocalized with markers of astrocytes (GFAP) and oligodendrocytes (RIP) in the ipsilateral hemisphere, and gliogenesis was enhanced in the subventricular zone of the rats treated with MSCs. This is the first report to show that MSCs injected at 7 days after stroke improve long-term neurological outcome in older animals. Brain tissue repair is an ongoing process with reactive gliosis, which persists for at least 4 months after stroke. Reactive astrocytes responding to MSC treatment of ischemia may also promote axonal regeneration during long-term recovery. © 2004 Wiley-Liss, Inc.