Preclinical Use of Group I Metabotropic Glutamate Receptors (Group I mGluRs) for Ischemic Stroke: Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.54536/ajmsi.v4i2.6056Keywords:
Agonist, Antagonist, Group I mGluRs, Ischemic Stroke, Preclinical StudiesAbstract
In ischemic stroke, metabotropic glutamate receptors (mGluRs) have a complex role. Results from studies using both agonists and antagonists of these receptors have been inconsistent. This systematic review and meta-analysis assesses multiple preclinical investigations on group I mGluR agonists and antagonists. Effect sizes for various outcomes, study quality scores, bias risk, and interactions with clinical factors related to functional and histological outcomes were analyzed based on relevant papers. Twelve papers covering 41 treatment groups of 26 interventions from 1999 to 2023 were included. Twelve studies (25 treatment arms) reported structural outcomes, while eight studies (16 treatment arms) reported functional outcomes, with a median quality score of 4 out of 10. Expected results showed larger effect sizes. The mean effect sizes for neurological score and infarct volume improved by -0.75 SMD and -1.37 SMD, respectively, after subgroup adjustments and sensitivity analysis. Effect sizes for neuroprotection, neuronal loss, brain temperature, and NMDA receptor activity with antagonist treatment were 1.73 SMD, -1.35 SMD, -0.05 SMD, and -0.41 SMD, respectively. While antagonists significantly (P < 0.05) improved both structural and functional outcomes, agonists only improved structural results. However, SYRCLE’s risk-of-bias tool for animal studies identified potential bias. Additionally, clinical variables such as dosage and administration mode of agonist or antagonist medications influenced the effect magnitude. Despite the promising results in preclinical studies, several drugs have failed to prevent ischemic stroke in human clinical trials. Future research using animal models of stroke is recommended to improve study quality, validity, and reduce the risk of bias.
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