Semaglutide Inhibits Neuronal Apoptosis and Improves Cognitive Function in Mice after Traumatic Brain Injury, Mainly...

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Traumatic brain injury (TBI) poses a significant global health challenge, with secondary injuries critically impacting outcomes.
• Semaglutide, a glucose-dependent hypoglycemic agent, has shown potential in mitigating neuroinflammation and cell death in neurodegenerative diseases.
• The specific role of semaglutide in TBI pathophysiology remains largely unexplored.

Purpose of the Study:

• To investigate the potential neuroprotective effects of semaglutide in a mouse model of TBI.
• To elucidate the mechanisms underlying semaglutide's impact on neuronal survival and neuroinflammation post-TBI.

Main Methods:

• Sixty male C57 mice were allocated into SHAM, TBI, and SEMAGLUTIDE (TBI + 50 nmol/kg/day semaglutide) groups.
• Neuroprotection was assessed 72 hours post-injury using behavioral tests, immunofluorescence, and Western blotting.

Main Results:

• Semaglutide treatment significantly reduced neuronal apoptosis by downregulating Bax and upregulating Bcl-2 expression.
• The drug modulated proteins in both caspase-dependent and independent apoptosis pathways, with a predominant effect on the former.
• Semaglutide inhibited M1 microglial activation, suggesting a role in reducing neuroinflammation.

Conclusions:

• Semaglutide administration enhanced neuronal survival and improved cognitive function in TBI mice.
• The observed neuroprotective effects are linked to the inhibition of apoptosis and M1 microglial activation.
• The therapeutic efficacy of semaglutide in TBI may be dependent on specific brain regions and treatment timing.