Int Neurourol J.  2016 May;20(Suppl 1):S49-S56.

Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury

• Shin MS
• Park HK
• Kim TW
• Ji ES
• Lee JM
• Choi HS
• Kim MY
• Kim YP

Abstract

PURPOSE
Traumatic brain injury (TBI) causes cognitive impairments, motor deficits, and neuropsychiatric/behavioral deficits problems. Transplantation of bone marrow stromal cells (BMSCs) facilitates functional recovery from brain insults. Treadmill exercise increases neurogenesis and inhibits apoptosis. In this study, we investigated the effects of BMSC transplantation in combination with treadmill exercise on memory function, by evaluating its effect on neurogenesis and apoptosis in the hippocampus following TBI.
METHODS
TBI was induced using an electromagnetic-controlled cortical impact device. BMSCs were transplanted into both sides of traumatic scar region 1 week after TBI induction. One week after transplantation of BMSCs, the rats in the exercise groups were trained to run on a treadmill for 30 minutes once daily for 28 days. Step-down avoidance task and radial 8-arm maze test were conducted. Levels of 5-bromo-2'-deoxyuridine and caspase-3 were evaluated using immunohistochemistry. Western blot was used to evaluate the expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), total-extracellular signal-regulated kinase 1 and 2 (t-ERK1/2), phosphorylated-ERK1/2 (p-ERK1/2), Bcl-2, and Bax.
RESULTS
TBI deteriorated memory function, suppressed neurogenesis, and accelerated apoptosis in the hippocampus. Treadmill exercise and BMSC transplantation independently improved memory function by increasing neurogenesis with suppression of apoptosis through the BDNF-ERK pathway in the TBI-induced rats. Combination of BMSC transplantation with treadmill exercise showed additional enhancement of neurogenesis and suppression of apoptosis in the hippocampus.
CONCLUSIONS
The present study shows that treadmill exercise may aid the therapeutic effect of BMSC transplantation on TBI in rats.

Keyword

Brain Injuries; Mesenchymal Stromal Cells; Exercise Test; Neurogenesis; Apoptosis

MeSH Terms

Animals
Apoptosis
Blotting, Western
Bone Marrow*
Brain
Brain Injuries*
Brain-Derived Neurotrophic Factor
Caspase 3
Cicatrix
Cognition Disorders
Exercise Test
Hippocampus
Immunohistochemistry
Memory
Mesenchymal Stromal Cells*
Neurogenesis
Neuroprotective Agents*
Phosphotransferases
Protein-Tyrosine Kinases
Rats