Intra-arterial transplantation of bone marrow mononuclear cells immediately after reperfusion decreases brain injury after focal ischemia in rats.
OBJECTIVE
Transplantation of bone marrow cells has been reported to exert neuroprotection against cerebral ischemia. However, the effect of bone marrow mononuclear cells (BMMCs) administered immediately after reperfusion has rarely been investigated. The present study was designed to examine whether brain injury in response to transient focal ischemia can be ameliorated by BMMC administration immediately after reperfusion in rats, and to determine whether there are differences in the route of administration.


METHODS
Autologous BMMCs were obtained from each rat. Rats were then subjected to transient focal ischemia followed by BMMC administration via the ipsilateral carotid artery (IA group) or the femoral vein (IV group) immediately after reperfusion. Control rats underwent the same procedure but received vehicle injection. Infarct volume was compared among the groups 24 h and 7 days after reperfusion. BMMCs were fluorescently labeled with PKH26 prior to administration to track transplanted cells.


RESULTS
Total infarct volume decreased in the IA group, but not in the IV group, when compared to the vehicle group. In the ipsilateral hemisphere, PKH26 positive cell count was greater in the IA group than in the IV group. Motor function, assessed with a rotarod test, improved in the IA group compared to the vehicle group.


CONCLUSIONS
These results show significant neuroprotection after transient focal ischemia by 1 x 10(7) autologous BMMCs administered intra-arterially, but not intravenously, immediately after reperfusion in rats. The larger number of transplanted BMMCs in the brain during the early stage of reperfusion may be responsible for the protective effect.
Kamiya
Nobuo
N
Division of Neurology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo113-8603, Japan. novo.k@nms.ac.jp
Ueda
Masayuki
M
Igarashi
Hironaka
H
Nishiyama
Yasuhiro
Y
Suda
Satoshi
S
Inaba
Toshiki
T
Katayama
Yasuo
Y
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000523:psychology; D002339:Carotid Arteries; D002544:Cerebral Infarction / Q000473:pathology; D005268:Femoral Vein; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D004856:Postural Balance / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D014182:Transplantation, Autologous