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While ionotropic glutamate receptors are traditional targets for neuroprotection, their direct inhibition often leads to severe side effects due to their critical roles in normal neurotransmission and synaptic plasticity. Group III mGluRs provide a more nuanced and potentially safer approach by modulating rather than blocking glutamatergic transmission. Their downstream signaling cascade results in the regulation of intracellular calcium levels, neuronal hyperpolarization, and reduced neurotransmitter release, effectively decreasing excitotoxic signaling without completely suppressing essential glutamatergic functions. Importantly, the neuroprotective effects of group III mGluRs extend beyond direct modulation of glutamate release influencing glial cell function, neuroinflammation, and oxidative stress, all of which contribute to secondary injury cascades in brain ischemia. This comprehensive analysis of group III mGluRs multifaceted neuroprotective potential provides valuable insights for developing novel therapeutic strategies to combat excitotoxicity in neonatal ischemic brain injury.<\/jats:p>","DOI":"10.1007\/s43440-024-00651-z","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T09:02:07Z","timestamp":1726736527000},"page":"1199-1218","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Group III metabotropic glutamate receptors: guardians against excitotoxicity in ischemic brain injury, with implications for neonatal contexts"],"prefix":"10.1007","volume":"76","author":[{"given":"Damian","family":"Mielecki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Sali\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"651_CR1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","volume":"50","author":"CM Niswender","year":"2010","unstructured":"Niswender CM, Conn PJ. 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