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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Exploring the Neuroprotective Effects of Mechanosensitive Channel Blocker, GsMTX4 in Intracerebral Hemorrhage Model in Rats

Wenyan Liu1, Guiyu Zhang1, Jin Wang1, Jing Liu1, Yu Yuan1, Jun Hong1, Yi Ding2★★ Corresponding author

  1. 1Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei, CHINA.
  2. 2Surgical Intensive Care Unit, Chongqing Jiangjin Central Hospital, Chongqing, CHINA.

CORRESPONDENCE

Yi Ding

Surgical Intensive Care Unit, Chongqing Jiangjin Central Hospital, Chongqing-402260, CHINA.

dingyi321654@sina.com

Received: 06-10-2020; Revised: 25-01-2021; Accepted: 12-04-2021.

Volume 55, Issue 3 · pp. 756–764 · PUBLISHED 2021 · DOI: 10.5530/ijper.55.3.148

View on IJPER original site ↗

ABSTRACT

Aim: The current study explored the usefulness of a mechanosensitive channel blocker, GsMTX4 in intracerebral hemorrhage (ICH)-associated deleterious effects along with the possible mechanisms. Materials and Methods: Type VII collagenase was administered in the right basal ganglia using stereotactic apparatus to induce ICH in rats. The ICH-associated injury was assessed using corner turn and forelimb placement tests (behavioral test); Evans blue extravasation test (blood-brain barrier damage), brain edema, apoptotic markers (caspase-3 and Bcl-2 levels). The levels of TNF-α (neuroinflammation), reactive oxygen species, and Brain-derived neurotrophic factor (BDNF) were also measured in ICH-subjected rats. GsMTx4, as a mechanosensitive channel blocker, and ANA-12, as a selective BDNF receptor blocker were employed as pharmacological agents. Results: Administration of GsMTx4 attenuated ICH-associated behavioral changes, preserved blood-brain barrier, prevented brain edema, and decreased apoptosis. GsMTx4 also decreased neuroinflammation and oxidative stress, while it increased the levels of BDNF. Moreover, administration of ANA-12 attenuated the neuroprotective effects of GsMTx4 suggesting that BDNF may be important in inducing neuroprotective effects of GsMTx4. Conclusion: GsMTx4 exerts neuroprotective effects in intracerebral hemorrhage-associated deleterious effects, which may be possibly due to an increase in BDNF levels along with a decrease in neuroinflammation and oxidative stress.

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    Liu, W., Zhang, G., Wang, J., Liu, J., Yuan, Y., Hong, J., & Ding, Y. (2021). Exploring the Neuroprotective Effects of Mechanosensitive Channel Blocker, GsMTX4 in Intracerebral Hemorrhage Model in Rats. Indian Journal of Pharmaceutical Education and Research, 55(3), 756–764. https://doi.org/10.5530/ijper.55.3.148