Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibition
Tetramethylpyrazine (TMP) is an active component of the Chuanxiong, effectively crosses blood-brain barrier (BBB). It exhibits neuroprotective potential in cerebral ischemia-reperfusion injury (CIRI). This study performed middle cerebral artery occlusion/reperfusion (MCAO/R) surgery in rats to evalu...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1594283/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850254058877616128 |
|---|---|
| author | Yixin Zhang Xin Zhang Xiaocheng Shi Weijing Liao Junbin Lin |
| author_facet | Yixin Zhang Xin Zhang Xiaocheng Shi Weijing Liao Junbin Lin |
| author_sort | Yixin Zhang |
| collection | DOAJ |
| description | Tetramethylpyrazine (TMP) is an active component of the Chuanxiong, effectively crosses blood-brain barrier (BBB). It exhibits neuroprotective potential in cerebral ischemia-reperfusion injury (CIRI). This study performed middle cerebral artery occlusion/reperfusion (MCAO/R) surgery in rats to evaluate TMP’s efficacy and mechanisms in mitigating CIRI. Rats received intraperitoneal TMP (40 mg/kg) for 3 days prior to MCAO/R and continued for 14 days post-surgery. Behavioral tests were conducted using mNSS and Morris water maze tests. Histopathological analyses, including HE, Nissl, and TUNEL staining. mRNA sequencing revealed that RhoA and ROCK2 were upregulated in the CIRI model and downregulated by TMP treatment. GO enrichment and KEGG enrichment showed RhoA and ROCK were related to neuroplasticity. Western blot and immunofluorescence staining confirmed that TMP inhibited RhoA, ROCK2, phosphorylated LIMK, and phosphorylated cofilin expression. Additionally, TMP increased the levels of neuroplasticity-related proteins PSD95 and MAP2, promoting synaptic and dendritic regeneration. Administration of lysophosphatidic acid (LPA), a RhoA/ROCK pathway agonist, attenuated TMP’s neuroprotective effects, validating the pathway’s role in TMP-mediated protection. These findings indicate that TMP confers neuroprotection in CIRI by inhibiting the RhoA/ROCK pathway and enhancing neuroplasticity, underscoring its therapeutic potential in CIRI. |
| format | Article |
| id | doaj-art-81a4bcd8428f420fb2eff54287da4600 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-81a4bcd8428f420fb2eff54287da46002025-08-20T01:57:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15942831594283Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibitionYixin ZhangXin ZhangXiaocheng ShiWeijing LiaoJunbin LinTetramethylpyrazine (TMP) is an active component of the Chuanxiong, effectively crosses blood-brain barrier (BBB). It exhibits neuroprotective potential in cerebral ischemia-reperfusion injury (CIRI). This study performed middle cerebral artery occlusion/reperfusion (MCAO/R) surgery in rats to evaluate TMP’s efficacy and mechanisms in mitigating CIRI. Rats received intraperitoneal TMP (40 mg/kg) for 3 days prior to MCAO/R and continued for 14 days post-surgery. Behavioral tests were conducted using mNSS and Morris water maze tests. Histopathological analyses, including HE, Nissl, and TUNEL staining. mRNA sequencing revealed that RhoA and ROCK2 were upregulated in the CIRI model and downregulated by TMP treatment. GO enrichment and KEGG enrichment showed RhoA and ROCK were related to neuroplasticity. Western blot and immunofluorescence staining confirmed that TMP inhibited RhoA, ROCK2, phosphorylated LIMK, and phosphorylated cofilin expression. Additionally, TMP increased the levels of neuroplasticity-related proteins PSD95 and MAP2, promoting synaptic and dendritic regeneration. Administration of lysophosphatidic acid (LPA), a RhoA/ROCK pathway agonist, attenuated TMP’s neuroprotective effects, validating the pathway’s role in TMP-mediated protection. These findings indicate that TMP confers neuroprotection in CIRI by inhibiting the RhoA/ROCK pathway and enhancing neuroplasticity, underscoring its therapeutic potential in CIRI.https://www.frontiersin.org/articles/10.3389/fphar.2025.1594283/fulltetramethylpyrazinecerebral ischemia-reperfusion injuryneuroplasticityneuroprotectionnature products |
| spellingShingle | Yixin Zhang Xin Zhang Xiaocheng Shi Weijing Liao Junbin Lin Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibition Frontiers in Pharmacology tetramethylpyrazine cerebral ischemia-reperfusion injury neuroplasticity neuroprotection nature products |
| title | Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibition |
| title_full | Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibition |
| title_fullStr | Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibition |
| title_full_unstemmed | Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibition |
| title_short | Tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia-reperfusion injury via RhoA/ROCK2 pathway inhibition |
| title_sort | tetramethylpyrazine enhances neuroprotection and plasticity in cerebral ischemia reperfusion injury via rhoa rock2 pathway inhibition |
| topic | tetramethylpyrazine cerebral ischemia-reperfusion injury neuroplasticity neuroprotection nature products |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1594283/full |
| work_keys_str_mv | AT yixinzhang tetramethylpyrazineenhancesneuroprotectionandplasticityincerebralischemiareperfusioninjuryviarhoarock2pathwayinhibition AT xinzhang tetramethylpyrazineenhancesneuroprotectionandplasticityincerebralischemiareperfusioninjuryviarhoarock2pathwayinhibition AT xiaochengshi tetramethylpyrazineenhancesneuroprotectionandplasticityincerebralischemiareperfusioninjuryviarhoarock2pathwayinhibition AT weijingliao tetramethylpyrazineenhancesneuroprotectionandplasticityincerebralischemiareperfusioninjuryviarhoarock2pathwayinhibition AT junbinlin tetramethylpyrazineenhancesneuroprotectionandplasticityincerebralischemiareperfusioninjuryviarhoarock2pathwayinhibition |