Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps

Objective To determine the activation of glial cells after brachial plexus injury (BPI), and to explore whether glatiramer acetate (GA) can improve the survival rate of spinal motoneurons of nerve stumps by inhibiting the activation of glial cells. Methods A nerve stumps model of 76 SD rats after BP...

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Main Authors: LI Liang, HUANG Jiajun, GU Liqiang
Format: Article
Language:zho
Published: The Editorial Department of Chinese Journal of Clinical Research 2024-12-01
Series:Zhongguo linchuang yanjiu
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Online Access:http://zglcyj.ijournals.cn/zglcyj/ch/reader/create_pdf.aspx?file_no=20241221
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author LI Liang
HUANG Jiajun
GU Liqiang
author_facet LI Liang
HUANG Jiajun
GU Liqiang
author_sort LI Liang
collection DOAJ
description Objective To determine the activation of glial cells after brachial plexus injury (BPI), and to explore whether glatiramer acetate (GA) can improve the survival rate of spinal motoneurons of nerve stumps by inhibiting the activation of glial cells. Methods A nerve stumps model of 76 SD rats after BPI was established by operation, and the rats were randomly divided into GA group (n=38) and control group (n=38). After operation, GA group was given subcutaneous injection of GA, and control group was given subcutaneous injection of normal saline of equal volume. The following indexes were detected at 5 time points on the 1st, 3rd, 7th, 14th, and 28th day after operation and administration. The cerebrospinal fluid(CSF)of rats was collected and the levels of tumor necrosis factor -α(TNF-α), interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) in CSF were measured by ELISA. The C5 stump and spinal cord were removed. The spinal cord was stained with Nissl to observe the histopathological changes. Immunohistochemistry and western blot were used to detect the astrocyte activation marker [glial fibrillary acidic protein (GFAP)] and microglia activation marker [ionic calcium adaptor protein-1 (Iba-1)] in spinal cord, and western blot was used to detect the synaptophysin (SYP) in spinal cord also. HE staining and immunohistochemical staining were used for detecting axonal growth marker [growth-associated protein 43 (GAP-43)] and Schwann cell marker S100 in nerve stump, and toluidine blue staining was used to observe myelinated nerve fiber density of regenerated nerve. Results The nerve stump model of all rats after BPI was successfully established. Compared with the control group at each time point after surgery and administration, TNF-α and IL-6 levels decreased and BDNF increased in the GA group (P<0.05);the survival percentage of motorneurons in the injured anterior horn increased in GA group (P<0.05);the expressions of GFAP and Iba-1 decreased and the expression of SYP increased in the GA group (P<0.01); the positive rates of GAP43 and S100 immunohistochemical staining per unit area of stump increased in GA group except for the first day (P<0.05); and the myelinated nerve fibers density in the stump increased in the GA group (P<0.05). In addition, HE staining of stump roots showed that the neural structure of the control group was chaotic and that of the GA group was orderly. Conclusion After BPI, glial cells are activated, the functional status of nerve stump and the number of spinal motoneurons in anterior horn of spinal cord decrease. GA-protected spinal motoneurons and their nerve stump functions are improved and maintained, and GA can inhibit the activation of microglia and astrocytes.
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spelling doaj-art-8546cd6b4af640e59bd64d7e6e7aecaa2024-12-30T07:17:22ZzhoThe Editorial Department of Chinese Journal of Clinical ResearchZhongguo linchuang yanjiu1674-81822024-12-0137121921 192710.13429/j.cnki.cjcr.2024.12.021Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumpsLI Liang0HUANG Jiajun1GU Liqiang2Department of Spine Surgery, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541002, ChinaDepartment of Spine Surgery, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541002, ChinaMicrosurgery Department of Hand Surgery, First Affiliated Hospital of Sun Yat sen University, Guangzhou, Guangdong 510080, ChinaObjective To determine the activation of glial cells after brachial plexus injury (BPI), and to explore whether glatiramer acetate (GA) can improve the survival rate of spinal motoneurons of nerve stumps by inhibiting the activation of glial cells. Methods A nerve stumps model of 76 SD rats after BPI was established by operation, and the rats were randomly divided into GA group (n=38) and control group (n=38). After operation, GA group was given subcutaneous injection of GA, and control group was given subcutaneous injection of normal saline of equal volume. The following indexes were detected at 5 time points on the 1st, 3rd, 7th, 14th, and 28th day after operation and administration. The cerebrospinal fluid(CSF)of rats was collected and the levels of tumor necrosis factor -α(TNF-α), interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) in CSF were measured by ELISA. The C5 stump and spinal cord were removed. The spinal cord was stained with Nissl to observe the histopathological changes. Immunohistochemistry and western blot were used to detect the astrocyte activation marker [glial fibrillary acidic protein (GFAP)] and microglia activation marker [ionic calcium adaptor protein-1 (Iba-1)] in spinal cord, and western blot was used to detect the synaptophysin (SYP) in spinal cord also. HE staining and immunohistochemical staining were used for detecting axonal growth marker [growth-associated protein 43 (GAP-43)] and Schwann cell marker S100 in nerve stump, and toluidine blue staining was used to observe myelinated nerve fiber density of regenerated nerve. Results The nerve stump model of all rats after BPI was successfully established. Compared with the control group at each time point after surgery and administration, TNF-α and IL-6 levels decreased and BDNF increased in the GA group (P<0.05);the survival percentage of motorneurons in the injured anterior horn increased in GA group (P<0.05);the expressions of GFAP and Iba-1 decreased and the expression of SYP increased in the GA group (P<0.01); the positive rates of GAP43 and S100 immunohistochemical staining per unit area of stump increased in GA group except for the first day (P<0.05); and the myelinated nerve fibers density in the stump increased in the GA group (P<0.05). In addition, HE staining of stump roots showed that the neural structure of the control group was chaotic and that of the GA group was orderly. Conclusion After BPI, glial cells are activated, the functional status of nerve stump and the number of spinal motoneurons in anterior horn of spinal cord decrease. GA-protected spinal motoneurons and their nerve stump functions are improved and maintained, and GA can inhibit the activation of microglia and astrocytes. http://zglcyj.ijournals.cn/zglcyj/ch/reader/create_pdf.aspx?file_no=20241221glatiramer acetatespinal motoneuronbrachial plexus injuryactivation of glial cellssynaptophysin
spellingShingle LI Liang
HUANG Jiajun
GU Liqiang
Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps
Zhongguo linchuang yanjiu
glatiramer acetate
spinal motoneuron
brachial plexus injury
activation of glial cells
synaptophysin
title Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps
title_full Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps
title_fullStr Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps
title_full_unstemmed Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps
title_short Experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps
title_sort experimental study on the protection of spinal motoneurons by using glatiramer acetate based on a rat model of nerve stumps
topic glatiramer acetate
spinal motoneuron
brachial plexus injury
activation of glial cells
synaptophysin
url http://zglcyj.ijournals.cn/zglcyj/ch/reader/create_pdf.aspx?file_no=20241221
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AT huangjiajun experimentalstudyontheprotectionofspinalmotoneuronsbyusingglatirameracetatebasedonaratmodelofnervestumps
AT guliqiang experimentalstudyontheprotectionofspinalmotoneuronsbyusingglatirameracetatebasedonaratmodelofnervestumps