Semaglutide Inhibits Neuronal Apoptosis and Improves Cognitive Function in Mice after Traumatic Brain Injury, Mainly via the Caspase-Dependent Pathway.

Xiyu Chen, Bin Zhang, Mengshi Yang, Yuan Zhuang, Xixian Liao, Guangzhi Shi

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Article in Neurocritical care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Xiyu Chen *Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

Bin Zhang *Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

Mengshi YangDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

Yuan ZhuangDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

Xixian LiaoDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

Guangzhi ShiDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China. shiguangzhi@bjtth.org.ORCID http://orcid.org/0000-0003-4189-5800

Funding

Beijing clinical key specialty project NO.2100199

6 · The paper itself

Abstract

backgroundTraumatic brain injury (TBI) is a global health problem, and its mechanisms can be divided into primary and secondary damage. Secondary injuries play a significant role in TBI outcomes. Recent studies have shown that semaglutide, a novel glucose-dependent hypoglycemic agent, inhibits neuroinflammation and cell death in some neurodegenerative diseases. However, the association between semaglutide level and TBI remains unclear. Therefore, this study aimed to investigate the neuroprotective effects of semaglutide in patients with TBI.

methodIn total, 60 C57 male mice were randomly divided into three groups: SHAM, TBI, and SEMAGLUTIDE (operation + 50 nmol/kg/day semaglutide). Behavioral tests, immunofluorescence, and western blotting were performed 72 h after impact.

resultsSemaglutide reduced neuronal apoptosis, downregulated Bax expression, and increased Bcl-2 expression after TBI. Additionally, in the downstream apoptosis pathway, semaglutide regulated proteins associated with caspase-dependent and caspase-independent pathways, with the caspase-dependent pathway being the major one. Moreover, the activation of M1 microglia was also inhibited by semaglutide, which may be related to its protective effects.

conclusionsSemaglutide inhibited apoptosis, increased neuronal survival rate, and inhibited M1 microglial activation to improve cognitive function in TBI mice. This neuroprotective effect of semaglutide may be regionally and time dependent. TRIAL REGISTRATION NUMBER: 202204008 Trial registration date: 2022Y12M3D.

Indexed as

ApoptosisBrain Injuries, TraumaticCognitionNeuronsNeuroprotective AgentsSemaglutideAnimalsCaspasesDisease Models, AnimalMaleMiceMice, Inbred C57BLSignal TransductionCaspasesNeuroprotective AgentsSemaglutideCaspase-3NeuroinflammationNeuronal survival rateSemaglutideTBI

Identifiers

PMID41644924

DOI10.1007/s12028-025-02446-3

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.