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

Indian Journal of Pharmaceutical Education and Research

  • Wenyan Liu1Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei, CHINA.
  • Guiyu Zhang1Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei, CHINA.
  • Jin Wang1Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei, CHINA.
  • Jing Liu1Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei, CHINA.
  • Yu Yuan1Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei, CHINA.
  • Jun Hong1Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei, CHINA.
  • Yi Ding2Surgical Intensive Care Unit, Chongqing Jiangjin Central Hospital, Chongqing, CHINA.

Volume 55 Issue 3 Pages 756-764

DOI: 10.5530/ijper.55.3.148

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.

Keywords

  • Neuroinflammation
  • Oxidative stress
  • Intracerebral hemorrhage
  • Mechanosensitive channels
  • BDNF
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