Evidence map›Paper›PMID 41871059›Full record

ArticlePloS one2026

Effects of GABAAR modulators CL218872 and MRK-016 on neural repair and synaptic plasticity in mice with Intracerebral hemorrhage.

Tingting Chen, Hongxia He, Fei Huang, Junwu Liu, Hongli Zhou, Lei Xu

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Article in PloS one, 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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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Tingting ChenWest China Hospital Sichuan University, Meishan Hospital, Meishan, China.
Hongxia HeWest China Hospital Sichuan University, Meishan Hospital, Meishan, China.
Fei HuangWest China Hospital Sichuan University, Meishan Hospital, Meishan, China.ORCID https://orcid.org/0009-0003-5701-9781
Junwu LiuWest China Hospital Sichuan University, Meishan Hospital, Meishan, China.
Hongli ZhouWest China Hospital Sichuan University, Meishan Hospital, Meishan, China.
Lei XuWest China Hospital Sichuan University, Meishan Hospital, Meishan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntracerebral hemorrhage (ICH) is a devastating condition characterized by rapid onset, high rates of disability and mortality, and prolonged recovery. Dysregulated γ-aminobutyric acid type A receptor (GABAAR) signaling contributes to ICH-induced neurotoxicity, presenting a promising therapeutic target.

objectiveTo assess the neurorestorative effects of the GABAAR α1-selective partial positive allosteric modulator (PAM) CL218872 and the α5-selective negative allosteric modulator (NAM) MRK-016 on synaptic plasticity and neural repair following ICH.

methodsAn ICH mouse model was constructed using collagenase IV, and ICH mice were administered the GABAAR modulators CL218872 or MRK-016. Differences in inflammation and neurological deficit score were compared between different groups of mice. Morphologic and functional changes in mouse neuronal cells were next determined by Nissl and Golgi-Cox staining. Synaptic structural changes in ICH mice were visualized by transmission electron microscopy, and changes in synaptic plasticity-related molecules were quantified to assess the effects of GABAAR modulators on synapses in ICH mice.

resultsTreatment with CL218872 resulted in a reduction in hemorrhage and improved neurobehavioral outcomes in ICH mice. Additionally, CL218872 mitigated inflammation by downregulating phospho-p65, IL-6 and TNF-α expression. Histological analysis revealed an increase in neuronal density, preservation of cell morphology, and enhanced synaptic connectivity following CL218872 treatment. Furthermore, synaptic structure was restored, and there was an upregulation of brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density protein 95 (PSD-95), and synaptophysin in ICH mice. However, treatment with MRK-016 yielded the opposite result.

conclusionThe GABAAR α1-selective PAM CL218872 exerts neuroprotective and neurorestorative effects in ICH, suggesting its therapeutic potential for ICH management.

Indexed as

Cerebral HemorrhageNeuronal PlasticityNeuroprotective AgentsReceptors, GABA-AAnimalsBrain-Derived Neurotrophic FactorDisease Models, AnimalMaleMiceMice, Inbred C57BLNeuronsSynapsesBrain-Derived Neurotrophic FactorNeuroprotective AgentsReceptors, GABA-A

Identifiers

PMID41871059
PMCPMC13008086

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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.