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Treatment of traumatic brain injury with a combination therapy of marrow stromal cells and atorvastatin in rats.
- Source :
-
Neurosurgery [Neurosurgery] 2007 Mar; Vol. 60 (3), pp. 546-53; discussion 553-4. - Publication Year :
- 2007
-
Abstract
- Objective: This study investigated the effects of a combination therapy of marrow stromal cells (MSCs) and statins (atorvastatin) after traumatic brain injury in rats.<br />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.<br />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.<br />Conclusion: When administered in combination with MSCs, atorvastatin increases MSC access and/or survival within the injured brain and enhances functional recovery compared with monotherapy.
- Subjects :
- Animals
Atorvastatin
Brain Injuries physiopathology
Combined Modality Therapy
Female
Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
Rats
Rats, Wistar
Stromal Cells transplantation
Treatment Outcome
Bone Marrow Transplantation
Brain Injuries pathology
Brain Injuries therapy
Hematopoietic Stem Cell Transplantation
Heptanoic Acids therapeutic use
Pyrroles therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4040
- Volume :
- 60
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neurosurgery
- Publication Type :
- Academic Journal
- Accession number :
- 17327800
- Full Text :
- https://doi.org/10.1227/01.NEU.0000255346.25959.99