Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats.
We investigated intra-arterially administered autologous bone marrow mononuclear cells (MNCs) in rats with acute ischemic stroke. Long Evans rats (2 to 3 months or 12 months old) underwent tandem reversible common carotid artery (CCA)/middle cerebral artery (MCA) occlusion (CCAo/MCAo) for 3 h and then 24 h later underwent tibial bone marrow harvest. Ten million or 4 million cells were re-injected by an intra-carotid infusion. Control animals underwent marrow needle insertion and then saline injection into the carotid artery. Animals were assessed on a battery of neurological tests. MNCs in the ischemic brain were tracked using Q-dot nanocrystal labeling. Infarct volume and cytokines in the ischemia-affected brain were analyzed. Cell-treated animals in the younger and older groups showed improvement from 7 to 30 days after stroke compared with vehicle-treated animals. MNCs significantly reduced infarct volume compared with saline. There was a significant reduction in tumor necrosis factor-alpha, interleukin-1alpha (IL-1alpha), IL-beta, IL-6, and a significant increase in IL-10 in injured brains harvested from the cell-treated groups compared with saline controls. Labeled MNCs were found in the peri-infarcted area at 1 h and exponentially decreased over the ensuing week after injection. Autologous bone marrow MNCs can be safely harvested from rodents after stroke, migrate to the peri-infarct area, enhance recovery, and modulate the post-ischemic inflammatory response.
Department ofNeurology, University of Texas, Houston Medical School, Houston, Texas 77030, USA.
Miranda
M
Brenneman
Sushil
S
Sharma
Matthew
M
Harting
Roger
R
Strong
Charles S
CS
Cox
Jarek
J
Aronowski
James C
JC
Grotta
Sean I
SI
Savitz
D000375:Aging / Q000502:physiology*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods / Q000502:physiology*; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D002544:Cerebral Infarction / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology; D007269:Injections, Intra-Arterial; D008297:Male; D009069:Movement Disorders / Q000209:etiology / Q000473:pathology; D010641:Phenotype; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000628:therapy*
D016207:Cytokines