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

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 ICHassociated 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 hemorrhageassociated deleterious effects, which may be possibly due to an increase in BDNF levels along with a decrease in neuroinflammation and oxidative stress.

Key words: Neuroinflammation, Oxidative stress, Intracerebral hemorrhage, Mechanosensitive channels, BDNF.