Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemia
Global cerebral ischemia (GCI), a severe form of ischemic stroke, leads to significant cognitive and neurological deficits, with neuroinflammation playing a central role in its pathophysiology. Trans-cinnamaldehyde (TCA), derived from Cinnamomum cassia (L.), has demonstrated anti-inflammatory and ne...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025002680 |
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| author | Xinjuan Liu Zhiyuan Lu Gaiying He Waimao Gao Kaifan Hu Jie Pan Yan Zhao Xingyu Wang Guang Yang Ying Xu |
| author_facet | Xinjuan Liu Zhiyuan Lu Gaiying He Waimao Gao Kaifan Hu Jie Pan Yan Zhao Xingyu Wang Guang Yang Ying Xu |
| author_sort | Xinjuan Liu |
| collection | DOAJ |
| description | Global cerebral ischemia (GCI), a severe form of ischemic stroke, leads to significant cognitive and neurological deficits, with neuroinflammation playing a central role in its pathophysiology. Trans-cinnamaldehyde (TCA), derived from Cinnamomum cassia (L.), has demonstrated anti-inflammatory and neuroprotective effects, but its role in GCI remains unclear. This study investigated whether TCA could ameliorate cognitive impairments in GCI rats by targeting neuroinflammation. A GCI rat model was established using the Pulsinelli four-vessel occlusion method. Behavioral tests, including the open field test, novel object recognition, and water maze, were conducted to assess cognitive function, while long-term potentiation (LTP) analysis was used to evaluate synaptic plasticity. Histological methods, including immunofluorescence and immunohistochemistry, assessed neuronal integrity and microglial activation in the hippocampus. Molecular techniques quantified synaptic protein expression, pro-inflammatory cytokines and TLR4/MyD88/MAPKs pathway activation in GCI rats and primary microglia. We found that TCA significantly improved learning and memory, as demonstrated by behavioral tests, and enhanced synaptic plasticity in GCI rats. Histological analysis revealed that TCA preserved neuronal morphology and inhibited microglial activation. Molecular assays confirmed that TCA reduced synaptic protein overexpression, decreased pro-inflammatory cytokine (IL-6, IL-1β, TNF-α) levels, and suppressed TLR4/MyD88/MAPKs pathway activation in GCI rats or primary microglia induced by LPS. In conclusion, TCA shows neuroprotective potential in GCI by modulating synaptic damage and microglia activation mediated by the TLR4/MyD88/MAPKs pathway and may serve as a therapeutic strategy for ischemic brain injury and related neurodegenerative conditions. |
| format | Article |
| id | doaj-art-30b9a197a72c44e098b2940fac91056e |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-30b9a197a72c44e098b2940fac91056e2025-08-20T03:57:56ZengElsevierBrain Research Bulletin1873-27472025-09-0122911145610.1016/j.brainresbull.2025.111456Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemiaXinjuan Liu0Zhiyuan Lu1Gaiying He2Waimao Gao3Kaifan Hu4Jie Pan5Yan Zhao6Xingyu Wang7Guang Yang8Ying Xu9Department of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaExperimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaDepartment of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Department of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Global cerebral ischemia (GCI), a severe form of ischemic stroke, leads to significant cognitive and neurological deficits, with neuroinflammation playing a central role in its pathophysiology. Trans-cinnamaldehyde (TCA), derived from Cinnamomum cassia (L.), has demonstrated anti-inflammatory and neuroprotective effects, but its role in GCI remains unclear. This study investigated whether TCA could ameliorate cognitive impairments in GCI rats by targeting neuroinflammation. A GCI rat model was established using the Pulsinelli four-vessel occlusion method. Behavioral tests, including the open field test, novel object recognition, and water maze, were conducted to assess cognitive function, while long-term potentiation (LTP) analysis was used to evaluate synaptic plasticity. Histological methods, including immunofluorescence and immunohistochemistry, assessed neuronal integrity and microglial activation in the hippocampus. Molecular techniques quantified synaptic protein expression, pro-inflammatory cytokines and TLR4/MyD88/MAPKs pathway activation in GCI rats and primary microglia. We found that TCA significantly improved learning and memory, as demonstrated by behavioral tests, and enhanced synaptic plasticity in GCI rats. Histological analysis revealed that TCA preserved neuronal morphology and inhibited microglial activation. Molecular assays confirmed that TCA reduced synaptic protein overexpression, decreased pro-inflammatory cytokine (IL-6, IL-1β, TNF-α) levels, and suppressed TLR4/MyD88/MAPKs pathway activation in GCI rats or primary microglia induced by LPS. In conclusion, TCA shows neuroprotective potential in GCI by modulating synaptic damage and microglia activation mediated by the TLR4/MyD88/MAPKs pathway and may serve as a therapeutic strategy for ischemic brain injury and related neurodegenerative conditions.http://www.sciencedirect.com/science/article/pii/S0361923025002680Trans-cinnamaldehydeGlobal cerebral ischemiaSynaptic plasticityMicroglia activationTLR4/MyD88/MAPKs pathway |
| spellingShingle | Xinjuan Liu Zhiyuan Lu Gaiying He Waimao Gao Kaifan Hu Jie Pan Yan Zhao Xingyu Wang Guang Yang Ying Xu Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemia Brain Research Bulletin Trans-cinnamaldehyde Global cerebral ischemia Synaptic plasticity Microglia activation TLR4/MyD88/MAPKs pathway |
| title | Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemia |
| title_full | Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemia |
| title_fullStr | Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemia |
| title_full_unstemmed | Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemia |
| title_short | Trans-cinnamaldehyde ameliorates neuroinflammation-mediated synaptic plasticity and memory impairment by blocking TLR4/MyD88/MAPKs pathway in global cerebral ischemia |
| title_sort | trans cinnamaldehyde ameliorates neuroinflammation mediated synaptic plasticity and memory impairment by blocking tlr4 myd88 mapks pathway in global cerebral ischemia |
| topic | Trans-cinnamaldehyde Global cerebral ischemia Synaptic plasticity Microglia activation TLR4/MyD88/MAPKs pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025002680 |
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