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

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 apopt...

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Main Authors: Mal Soon Shin, Hun Kyung Park, Tae Woon Kim, Eun Sang Ji, Jae Min Lee, Han Sung Choi, Mi Ye Kim, Young Pyo Kim
Format: Article
Language:English
Published: Korean Continence Society 2016-05-01
Series:International Neurourology Journal
Subjects:
Online Access:http://www.einj.org/upload/pdf/inj-1632616-308.pdf
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author Mal Soon Shin
Hun Kyung Park
Tae Woon Kim
Eun Sang Ji
Jae Min Lee
Han Sung Choi
Mi Ye Kim
Young Pyo Kim
author_facet Mal Soon Shin
Hun Kyung Park
Tae Woon Kim
Eun Sang Ji
Jae Min Lee
Han Sung Choi
Mi Ye Kim
Young Pyo Kim
author_sort Mal Soon Shin
collection DOAJ
description 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-2ʹ-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.
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spelling doaj.art-608e376b718f4c8d9e80c82ddd256e652022-12-21T23:44:36ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312016-05-0120Suppl 1S495610.5213/inj.1632616.308583Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain InjuryMal Soon Shin0Hun Kyung Park1Tae Woon Kim2Eun Sang Ji3Jae Min Lee4Han Sung Choi5Mi Ye Kim6Young Pyo Kim7 School of Global Sport Studies, Korea University, Sejong, Korea Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea Department of Emergency Medicine, College of Medicine, Kyung Hee University, Seoul, Korea Department of Kinesiology, College of Natural Science, Jeju National University, Jeju, Korea Department of Kinesiology, College of Natural Science, Jeju National University, Jeju, KoreaPurpose: 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-2ʹ-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.http://www.einj.org/upload/pdf/inj-1632616-308.pdfBrain InjuriesMesenchymal Stromal CellsExercise TestNeurogenesisApoptosis
spellingShingle Mal Soon Shin
Hun Kyung Park
Tae Woon Kim
Eun Sang Ji
Jae Min Lee
Han Sung Choi
Mi Ye Kim
Young Pyo Kim
Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury
International Neurourology Journal
Brain Injuries
Mesenchymal Stromal Cells
Exercise Test
Neurogenesis
Apoptosis
title Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury
title_full Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury
title_fullStr Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury
title_full_unstemmed Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury
title_short Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury
title_sort neuroprotective effects of bone marrow stromal cell transplantation in combination with treadmill exercise following traumatic brain injury
topic Brain Injuries
Mesenchymal Stromal Cells
Exercise Test
Neurogenesis
Apoptosis
url http://www.einj.org/upload/pdf/inj-1632616-308.pdf
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