Gui-Hua Wang1, Yang Liu2, Xiao-Bing Wu3, Ying Lu4, Jin Liu3, Ya-Ru Qin3, Tong Li5, Hai-Feng Duan6. 1. Department of Neurology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China; Beijing Institute of Radiation Medicine, Beijing, China. 2. College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China. 3. Beijing Institute of Radiation Medicine, Beijing, China. 4. No. 307 Hospital of the Chinese People's Liberation Army, Beijing, China. 5. Department of Neurology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China. Electronic address: litong0883@163.com. 6. Beijing Institute of Radiation Medicine, Beijing, China. Electronic address: dhf553@163.com.
Abstract
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) possess the ability to repair brain injuries. Additionally, nimodipine is a neuroprotective agent that increases cerebral blood flow and may help with the homing of MSCs to the injury site. Here we investigate the effectiveness of a combined human umbilical cord-derived MSCs and nimodipine therapy in radiation-induced brain injury (RIBI). METHODS: Female mice received whole brain irradiation (WBI) and were treated with saline, nimodipine, hUC-MSCs, or hUC-MSCs combined with nimodipine. Body weight was measured weekly. An open field test for locomotor activity and a step-down avoidance test for learning and memory function were conducted at week 4 and week 12 post-WBI. The histological damage was evaluated by hematoxylin and eosin staining and glial fibrillary acidic protein immunohistochemistry. Quantitative polymerase chain reaction and Western blotting were used to detect apoptosis-related mediators (p53, Bax and Bcl-2). RESULTS: In mice receiving the hUC-MSCs or the combined treatment, their body weight recovered, their locomotor and cognitive ability improved, and the percentage of necrotic neurons and astrocytes was reduced. The combined therapy was significantly (P < 0.05) more effective than hUC-MSCs alone; these mice showed decreased expression of pro-apoptotic indicators (p53, Bax) and increased expression of an anti-apoptotic indicator (Bcl-2), which may protect brain cells. CONCLUSIONS: We demonstrated that hUC-MSCs therapy helps recover body weight loss and behavior dysfunction in a mice model of RIBI. Moreover, the effectiveness of the combined hUC-MSCs and nimodipine therapy is due to apoptosis inhibition and enhancing homing of MSCs to the injured brain.
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) possess the ability to repair brain injuries. Additionally, nimodipine is a neuroprotective agent that increases cerebral blood flow and may help with the homing of MSCs to the injury site. Here we investigate the effectiveness of a combined human umbilical cord-derived MSCs and nimodipine therapy in radiation-induced brain injury (RIBI). METHODS: Female mice received whole brain irradiation (WBI) and were treated with saline, nimodipine, hUC-MSCs, or hUC-MSCs combined with nimodipine. Body weight was measured weekly. An open field test for locomotor activity and a step-down avoidance test for learning and memory function were conducted at week 4 and week 12 post-WBI. The histological damage was evaluated by hematoxylin and eosin staining and glial fibrillary acidic protein immunohistochemistry. Quantitative polymerase chain reaction and Western blotting were used to detect apoptosis-related mediators (p53, Bax and Bcl-2). RESULTS: In mice receiving the hUC-MSCs or the combined treatment, their body weight recovered, their locomotor and cognitive ability improved, and the percentage of necrotic neurons and astrocytes was reduced. The combined therapy was significantly (P < 0.05) more effective than hUC-MSCs alone; these mice showed decreased expression of pro-apoptotic indicators (p53, Bax) and increased expression of an anti-apoptotic indicator (Bcl-2), which may protect brain cells. CONCLUSIONS: We demonstrated that hUC-MSCs therapy helps recover body weight loss and behavior dysfunction in a mice model of RIBI. Moreover, the effectiveness of the combined hUC-MSCs and nimodipine therapy is due to apoptosis inhibition and enhancing homing of MSCs to the injured brain.
Authors: Raghavan Chinnadurai; Paul D Bates; Keith A Kunugi; Kwangok P Nickel; Larry A DeWerd; Christian M Capitini; Jacques Galipeau; Randall J Kimple Journal: Front Immunol Date: 2021-07-26 Impact factor: 7.561