Treatment of traumatic brain injury with a combination therapy of marrow stromal cells and atorvastatin in rats.
OBJECTIVE
This study investigated the effects of a combination therapy of marrow stromal cells (MSCs) and statins (atorvastatin) after traumatic brain injury in rats.


METHODS
Thirty-two female Wistar rats were injured by controlled cortical impact and divided into four groups. Group I was injected with MSCs (1 x 10(6)) intravenously 24 hrs after traumatic brain injury. Group II was administered atorvastatin (0.5 mg/kg) orally for 14 days starting 24 hours after traumatic brain injury. Group III received MSCs (1 x 10(6)) combined with atorvastatin (0.5 mg/kg). Group IV (control) was injected with saline. MSCs were harvested from the bone marrow of male rats to identify male donor cells within female recipient animals by localization of Y chromosomes. Functional analysis was performed using modified neurological severity scores and the Morris water maze test. Animals were sacrificed 35 days after injury and brain sections stained with immunohistochemistry.


RESULTS
No functional improvement was seen in animals treated with MSCs or atorvastatin alone (Groups I and II). However, functional improvement was seen with both testing modalities (modified neurological severity scores and Morris water maze) in animals receiving combination therapy (Group III). Microscopic analysis showed that significantly more MSCs were present in animals receiving combination therapy than in those receiving MSCs alone. Also, significantly more endogenous cellular proliferation was seen in the hippocampus and injury boundary zone of the combination therapy group than in the monotherapy or control groups.


CONCLUSIONS
When administered in combination with MSCs, atorvastatin increases MSC access and/or survival within the injured brain and enhances functional recovery compared with monotherapy.
Mahmood
Asim
A
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA. nsaam@neuro.hfh.edu
Lu
Dunyue
D
Qu
Changsheng
C
Goussev
Anton
A
Chopp
Michael
M
D000818:Animals; D000069059:Atorvastatin; D016026:Bone Marrow Transplantation; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000637:transplantation; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin