Autologous bone marrow mononuclear cells therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.
BACKGROUND
Autologous bone marrow-derived mononuclear cells (AMNCs) have shown therapeutic promise for central nervous system insults such as stroke and traumatic brain injury (TBI). We hypothesized that intravenous injection of AMNC provides neuroprotection, which leads to cognitive improvement after TBI.


METHODS
A controlled cortical impact (CCI) rodent TBI model was used to examine blood-brain barrier (BBB) permeability, neuronal and glial apoptosis, as well as cognitive behavior. Two groups of rats underwent CCI with AMNC treatment (CCI-autologous) or without AMNC treatment (CCI-alone), consisting of 2 million AMNC per kilogram body weight harvested from the tibia and intravenously injected 72 hours after injury. CCI-alone animals underwent sham harvests and received vehicle injections.


RESULTS
Ninety-six hours after injury, AMNC significantly reduced the BBB permeability in injured animals, and there was an increase in apoptosis of proinflammatory activated microglia in the ipsilateral hippocampus. At 4 weeks after injury, we observed significant improvement in probe testing of CCI-Autologous group in comparison to CCI-Alone in the Morris Water Maze paradigm.


CONCLUSIONS
Our data demonstrate that the intravenous injection of AMNC after TBI leads to neuroprotection by preserving early BBB integrity, increasing activated microglial apoptosis and improving cognitive function.
From the Departments of Pediatric Surgery (S.S.B., P.A.W., S.K.S., F.J., C.P.T., P.S., R.A.H., H.X., C.S.C.), Surgery (P.A.W., S.K.S., R.A.H., H.X., C.S.C.), and Neurobiology and Anatomy (P.K.D.), University of Texas, Health Science Center at Houston, Houston; and Michael E DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices (S.K.S.), Texas A & M University, College Station, Texas; and Blood Systems Research Institute (S.P.); and Department of Laboratory Medicine (S.P.), University of California San Francisco, San Francisco, California.
Supinder S
SS
Bedi
Peter A
PA
Walker
Shinil K
SK
Shah
Fernando
F
Jimenez
Chelsea P
CP
Thomas
Philippa
P
Smith
Robert A
RA
Hetz
Hasen
H
Xue
Shibani
S
Pati
Pramod K
PK
Dash
Charles S
CS
Cox
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001812:Blood-Brain Barrier / Q000503:physiopathology; D016026:Bone Marrow Transplantation / Q000379:methods*; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology / Q000601:surgery*; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D017628:Microglia / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley