Original Article

Journal of Cerebral Blood Flow & Metabolism (2000) 20, 1311–1319; doi:10.1097/00004647-200009000-00006

Intrastriatal Transplantation of Bone Marrow Nonhematopoietic Cells Improves Functional Recovery After Stroke in Adult Mice

Supported by NINDS grants PO1 NS23393 and RO1 NS35504.

Yi Li*, Michael Chopp*,, Jieli Chen*, Lei Wang*, Subhash C Gautam, Yong-Xian Xu and Zhenggang Zhang*

  1. *Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan, U.S.A.
  2. Department of Physics, Oakland University, Rochester, Michigan, U.S.A.
  3. Division of Hematology/Oncology, Henry Ford Health Sciences Center, Detroit, Michigan, U.S.A.

Correspondence: Michael Chopp, Henry Ford Hospital Neurology Department, 2799 West Grand Boulevard, Detroit, MI 48202, U.S.A.

Received 19 April 2000; Revised 31 May 2000; Accepted 31 May 2000.

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Abstract

The authors transplanted adult bone marrow nonhematopoietic cells into the striatum after embolic middle cerebral artery occlusion (MCAO). Mice (n = 23; C57BL/6J) were divided into four groups: (1) mice (n = 5) were subjected to MCAO and transplanted with bone marrow nonhematopoietic cells (prelabeled by bromodeoxyuridine, BrdU) into the ischemic striatum, (2) MCAO alone (n = 8), (3) MCAO with injection of phosphate buffered saline (n = 5), and (4) bone marrow nonhematopoietic cells injected into the normal striatum (n = 5). Mice were killed at 28 days after stroke. BrdU reactive cells survived and migrated a distance of approximately 2.2 mm from the grafting areas toward the ischemic areas. BrdU reactive cells expressed the neuronal specific protein NeuN in 1% of BrdU stained cells and the astrocytic specific protein glial fibrillary acidic protein (GFAP) in 8% of the BrdU stained cells. Functional recovery from a rotarod test (P < 0.05) and modified neurologic severity score tests (including motor, sensory, and reflex;P < 0.05) were significantly improved in the mice receiving bone marrow nonhematopoietic cells compared with MCAO alone. The current findings suggest that the intrastriatal transplanted bone marrow nonhematopoietic cells survived in the ischemic brain and improved functional recovery of adult mice even though infarct volumes did not change significantly. Bone marrow nonhematopoietic cells may provide a new avenue to promote recovery of injured brain.

Keywords:

Bone marrow cells, Transplantation, Stroke, Mice

Abbreviations:

BMPs, bone morphogenetic proteins; BrdU, bromodeoxyuridine; DAB, 3,3'-diaminobenzidine; 5-FU, 5-fluorouracil; GFAP, glial fibrillary acidic protein; H&E, hematoxylin and eosin; HSCs, hematopoietic stem and progenitor cells; MCAO, middle cerebral artery occlusion; MSCs, marrow stromal cells; NSS, neurologic severity score; PBS, phosphate-buffered saline

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