Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes
2,3,5,6-Tetramethylpyrazine (TMP) as an active ingredient extracted from a traditional Chinese herbal medicine Ligusticum chuanxiong Hort. has been proved to penetrate blood-brain barrier (BBB) and show neuroprotective effects on cerebral ischemia. However, whether TMP could regulate astrocytic reac...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1125412/full |
| _version_ | 1827979198033035264 |
|---|---|
| author | Xue-feng Feng Xue-feng Feng Ming-cong Li Ming-cong Li Zi-yue Lin Zi-yue Lin Man-zhong Li Man-zhong Li Yun Lu Yun Lu Yu-ming Zhuang Yu-ming Zhuang Jian-feng Lei Lei Wang Lei Wang Hui Zhao Hui Zhao |
| author_facet | Xue-feng Feng Xue-feng Feng Ming-cong Li Ming-cong Li Zi-yue Lin Zi-yue Lin Man-zhong Li Man-zhong Li Yun Lu Yun Lu Yu-ming Zhuang Yu-ming Zhuang Jian-feng Lei Lei Wang Lei Wang Hui Zhao Hui Zhao |
| author_sort | Xue-feng Feng |
| collection | DOAJ |
| description | 2,3,5,6-Tetramethylpyrazine (TMP) as an active ingredient extracted from a traditional Chinese herbal medicine Ligusticum chuanxiong Hort. has been proved to penetrate blood-brain barrier (BBB) and show neuroprotective effects on cerebral ischemia. However, whether TMP could regulate astrocytic reactivity to facilitate neurovascular restoration in the subacute ischemic stroke needs to be urgently verified. In this research, permanent occlusion of the middle cerebral artery (MCAO) model was conducted and TMP (10, 20, 40 mg/kg) was intraperitoneally administrated to rats once daily for 2 weeks. Neurological function was evaluated by motor deficit score (MDS). Magnetic resonance imaging (MRI) was implemented to analyze tissue injury and cerebral blood flow (CBF). Magnetic resonance angiography (MRA) was applied to exhibit vascular signals. Transmission electron microscopy (TEM) was performed to detect the neurovascular unit (NVU) ultrastructure. Haematoxylin and eosin (HE) staining was utilized to evaluate cerebral histopathological lesions. The neurogenesis, angiogenesis, A1/A2 reactivity, aquaporin 4 (AQP4) and connexin 43 (Cx43) of astrocytes were observed with immunofluorescent staining. Then FGF2/PI3K/AKT signals were measured by western blot. Findings revealed TMP ameliorated neurological functional recovery, preserved NVU integrity, and enhanced endogenous neurogenesis and angiogenesis of rats with subacute ischemia. Shifting A1 to A2 reactivity, suppressing excessive AQP4 and Cx43 expression of astrocytes, and activating FGF2/PI3K/AKT pathway might be potential mechanisms of promoting neurovascular restoration with TMP after ischemic stroke. |
| first_indexed | 2024-04-09T21:33:30Z |
| format | Article |
| id | doaj.art-39d1e6d6344c4cbd98a91d658f0116df |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-09T21:33:30Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-39d1e6d6344c4cbd98a91d658f0116df2023-03-27T05:52:31ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-03-011710.3389/fncel.2023.11254121125412Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytesXue-feng Feng0Xue-feng Feng1Ming-cong Li2Ming-cong Li3Zi-yue Lin4Zi-yue Lin5Man-zhong Li6Man-zhong Li7Yun Lu8Yun Lu9Yu-ming Zhuang10Yu-ming Zhuang11Jian-feng Lei12Lei Wang13Lei Wang14Hui Zhao15Hui Zhao16School 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, 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, China2,3,5,6-Tetramethylpyrazine (TMP) as an active ingredient extracted from a traditional Chinese herbal medicine Ligusticum chuanxiong Hort. has been proved to penetrate blood-brain barrier (BBB) and show neuroprotective effects on cerebral ischemia. However, whether TMP could regulate astrocytic reactivity to facilitate neurovascular restoration in the subacute ischemic stroke needs to be urgently verified. In this research, permanent occlusion of the middle cerebral artery (MCAO) model was conducted and TMP (10, 20, 40 mg/kg) was intraperitoneally administrated to rats once daily for 2 weeks. Neurological function was evaluated by motor deficit score (MDS). Magnetic resonance imaging (MRI) was implemented to analyze tissue injury and cerebral blood flow (CBF). Magnetic resonance angiography (MRA) was applied to exhibit vascular signals. Transmission electron microscopy (TEM) was performed to detect the neurovascular unit (NVU) ultrastructure. Haematoxylin and eosin (HE) staining was utilized to evaluate cerebral histopathological lesions. The neurogenesis, angiogenesis, A1/A2 reactivity, aquaporin 4 (AQP4) and connexin 43 (Cx43) of astrocytes were observed with immunofluorescent staining. Then FGF2/PI3K/AKT signals were measured by western blot. Findings revealed TMP ameliorated neurological functional recovery, preserved NVU integrity, and enhanced endogenous neurogenesis and angiogenesis of rats with subacute ischemia. Shifting A1 to A2 reactivity, suppressing excessive AQP4 and Cx43 expression of astrocytes, and activating FGF2/PI3K/AKT pathway might be potential mechanisms of promoting neurovascular restoration with TMP after ischemic stroke.https://www.frontiersin.org/articles/10.3389/fncel.2023.1125412/fulltetramethylpyrazineischemic strokeneurogenesisangiogenesisastrocytesneurovascular unit |
| spellingShingle | Xue-feng Feng Xue-feng Feng Ming-cong Li Ming-cong Li Zi-yue Lin Zi-yue Lin Man-zhong Li Man-zhong Li Yun Lu Yun Lu Yu-ming Zhuang Yu-ming Zhuang Jian-feng Lei Lei Wang Lei Wang Hui Zhao Hui Zhao Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes Frontiers in Cellular Neuroscience tetramethylpyrazine ischemic stroke neurogenesis angiogenesis astrocytes neurovascular unit |
| title | Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes |
| title_full | Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes |
| title_fullStr | Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes |
| title_full_unstemmed | Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes |
| title_short | Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes |
| title_sort | tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of a1 a2 reactive astrocytes |
| topic | tetramethylpyrazine ischemic stroke neurogenesis angiogenesis astrocytes neurovascular unit |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1125412/full |
| work_keys_str_mv | AT xuefengfeng tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT xuefengfeng tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT mingcongli tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT mingcongli tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT ziyuelin tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT ziyuelin tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT manzhongli tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT manzhongli tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT yunlu tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT yunlu tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT yumingzhuang tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT yumingzhuang tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT jianfenglei tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT leiwang tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT leiwang tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT huizhao tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes AT huizhao tetramethylpyrazinepromotesstrokerecoverybyinducingtherestorationofneurovascularunitandtransformationofa1a2reactiveastrocytes |