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Maintenance of these neurotransmitters pools is strictly relying on the de novo synthesis of glutamine in astrocytes. Cerebral ischemic events disrupt the balance in uptake and re-synthesis, altering Glu, GABA, and glutamine (Gln) levels.\u00a0We focused on the determining of the ratios of glutamate, GABA and glutamine in the brain of rats in the intact state, the early changes and temporal development of changes towards the recovery after disruption of balance by global cerebral ischemia.\u00a0Animals underwent 15\u00a0min of global cerebral ischemia, and changes in Glu\/GABA\/Gln ratios in the hippocampus, cortex, and cerebellum were assessed at 3\u00a0h, 24\u00a0h, and 72\u00a0h post-reperfusion using high-resolution NMR. Ischemic preconditioning was also used to induce tolerance.\u00a0In an intact rat brain, glutamate level was about twice that of glutamine in all substructures, about sevenfold compared to GABA in the hippocampus and cortex, and almost eightfold compared to GABA in the cerebellum. There were three to four times as much glutamine compared to GABA. After severe cerebral ischemia, Glu\/Gln as well as GABA\/Gln ratios extensively dropped in early reperfusion (3\u00a0h) and gradually increased in 72\u00a0h reperfusion time, however, only the Glu\/Gln ratio recovered to the level of controls. Glu\/GABA ratio remained in all three reperfusion times over the level of control animals. We observed a decrease in glutathione NMR peak in brain tissue homogenates after ischemia.\u00a0The obtained data suggest the accelerated accumulation of intraparenchymal glutamate after ischemia, which was even more pronounced in the preconditioned animals three days after an ischemic event. The postischemic GABA level restoration did not achieve the level before ischemia in 72\u00a0h reperfusion, which could be one of the limiting factors in the complete postischemic GABA transmission recovery. Presented data may be of advantage not only when comparing glutamate and GABA homeostasis and neurotransmission, but also for glutamine reserve display as neurotransmitter precursor and ammonia transfer buffer in glutamate\/GABA\/glutamine cycle within the intact brain substructures as well after ischemic insult in rats.<\/jats:p>","DOI":"10.1007\/s11011-024-01511-8","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T07:30:01Z","timestamp":1738913401000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Glutamate\/GABA\/glutamine ratios in intact and ischemia reperfusion challenged rat brain subregions, the effect of ischemic preconditioning"],"prefix":"10.1007","volume":"40","author":[{"given":"Eva","family":"Baranovicova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Kalenska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lehotsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"1511_CR1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.pneurobio.2008.08.002","volume":"86","author":"MC Angulo","year":"2008","unstructured":"Angulo MC, Le Meur K, Kozlov AS et al (2008) GABA, a forgotten gliotransmitter. 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