Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats
Ischemic stroke elicits white matter injury typically signed by axonal disintegration and demyelination; thus, the development of white matter reorganization is needed. 2,3,5,6-Tetramethylpyrazine (TMP) is widely used to treat ischemic stroke. This study was aimed to investigate whether TMP could pr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.851746/full |
| _version_ | 1828350318215168000 |
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| author | Xue-Feng Feng Xue-Feng Feng Jian-Feng Lei Man-Zhong Li Man-Zhong Li Yu Zhan Yu Zhan Le Yang Le Yang Yun Lu Yun Lu Ming-Cong Li Ming-Cong Li Yu-Ming Zhuang Yu-Ming Zhuang Lei Wang Lei Wang Hui Zhao Hui Zhao |
| author_facet | Xue-Feng Feng Xue-Feng Feng Jian-Feng Lei Man-Zhong Li Man-Zhong Li Yu Zhan Yu Zhan Le Yang Le Yang Yun Lu Yun Lu Ming-Cong Li Ming-Cong Li Yu-Ming Zhuang Yu-Ming Zhuang Lei Wang Lei Wang Hui Zhao Hui Zhao |
| author_sort | Xue-Feng Feng |
| collection | DOAJ |
| description | Ischemic stroke elicits white matter injury typically signed by axonal disintegration and demyelination; thus, the development of white matter reorganization is needed. 2,3,5,6-Tetramethylpyrazine (TMP) is widely used to treat ischemic stroke. This study was aimed to investigate whether TMP could protect the white matter and promote axonal repair after cerebral ischemia. Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with TMP (10, 20, 40 mg/kg) intraperitoneally for 14 days. The motor function related to gait was evaluated by the gait analysis system. Multiparametric magnetic resonance imaging (MRI) was conducted to noninvasively identify gray-white matter structural integrity, axonal reorganization, and cerebral blood flow (CBF), followed by histological analysis. The expressions of axonal growth-associated protein 43 (GAP-43), synaptophysin (SYN), axonal growth-inhibitory signals, and guidance factors were measured by Western blot. Our results showed TMP reduced infarct volume, relieved gray-white matter damage, promoted axonal remodeling, and restored CBF along the peri-infarct cortex, external capsule, and internal capsule. These MRI findings were confirmed by histopathological data. Moreover, motor function, especially gait impairment, was improved by TMP treatment. Notably, TMP upregulated GAP-43 and SYN and enhanced axonal guidance cues such as Netrin-1/DCC and Slit-2/Robo-1 but downregulated intrinsic growth-inhibitory signals NogoA/NgR/RhoA/ROCK-2. Taken together, our data indicated that TMP facilitated poststroke axonal remodeling and motor functional recovery. Moreover, our findings suggested that TMP restored local CBF, augmented guidance cues, and restrained intrinsic growth-inhibitory signals, all of which might improve the intracerebral microenvironment of ischemic areas and then benefit white matter remodeling. |
| first_indexed | 2024-04-14T01:23:15Z |
| format | Article |
| id | doaj.art-1b7499026103438da5eecb2477110d67 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T01:23:15Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-1b7499026103438da5eecb2477110d672022-12-22T02:20:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.851746851746Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated RatsXue-Feng Feng0Xue-Feng Feng1Jian-Feng Lei2Man-Zhong Li3Man-Zhong Li4Yu Zhan5Yu Zhan6Le Yang7Le Yang8Yun Lu9Yun Lu10Ming-Cong Li11Ming-Cong Li12Yu-Ming Zhuang13Yu-Ming Zhuang14Lei Wang15Lei Wang16Hui Zhao17Hui Zhao18School of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaMedical Imaging Laboratory of Core Facility Center, Capital Medical University, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaBeijing Key Lab of TCM Collateral Disease Theory Research, Beijing, ChinaIschemic stroke elicits white matter injury typically signed by axonal disintegration and demyelination; thus, the development of white matter reorganization is needed. 2,3,5,6-Tetramethylpyrazine (TMP) is widely used to treat ischemic stroke. This study was aimed to investigate whether TMP could protect the white matter and promote axonal repair after cerebral ischemia. Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with TMP (10, 20, 40 mg/kg) intraperitoneally for 14 days. The motor function related to gait was evaluated by the gait analysis system. Multiparametric magnetic resonance imaging (MRI) was conducted to noninvasively identify gray-white matter structural integrity, axonal reorganization, and cerebral blood flow (CBF), followed by histological analysis. The expressions of axonal growth-associated protein 43 (GAP-43), synaptophysin (SYN), axonal growth-inhibitory signals, and guidance factors were measured by Western blot. Our results showed TMP reduced infarct volume, relieved gray-white matter damage, promoted axonal remodeling, and restored CBF along the peri-infarct cortex, external capsule, and internal capsule. These MRI findings were confirmed by histopathological data. Moreover, motor function, especially gait impairment, was improved by TMP treatment. Notably, TMP upregulated GAP-43 and SYN and enhanced axonal guidance cues such as Netrin-1/DCC and Slit-2/Robo-1 but downregulated intrinsic growth-inhibitory signals NogoA/NgR/RhoA/ROCK-2. Taken together, our data indicated that TMP facilitated poststroke axonal remodeling and motor functional recovery. Moreover, our findings suggested that TMP restored local CBF, augmented guidance cues, and restrained intrinsic growth-inhibitory signals, all of which might improve the intracerebral microenvironment of ischemic areas and then benefit white matter remodeling.https://www.frontiersin.org/articles/10.3389/fphar.2022.851746/fulltetramethylpyrazineischemic strokeaxonal remodelingsynaptic plasticitywhite matter reorganization |
| spellingShingle | Xue-Feng Feng Xue-Feng Feng Jian-Feng Lei Man-Zhong Li Man-Zhong Li Yu Zhan Yu Zhan Le Yang Le Yang Yun Lu Yun Lu Ming-Cong Li Ming-Cong Li Yu-Ming Zhuang Yu-Ming Zhuang Lei Wang Lei Wang Hui Zhao Hui Zhao Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats Frontiers in Pharmacology tetramethylpyrazine ischemic stroke axonal remodeling synaptic plasticity white matter reorganization |
| title | Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats |
| title_full | Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats |
| title_fullStr | Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats |
| title_full_unstemmed | Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats |
| title_short | Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats |
| title_sort | magnetic resonance imaging investigation of neuroplasticity after ischemic stroke in tetramethylpyrazine treated rats |
| topic | tetramethylpyrazine ischemic stroke axonal remodeling synaptic plasticity white matter reorganization |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.851746/full |
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