Remote Ischaemic Preconditioning Accelerates Brain to Blood Glutamate Efflux via EAATs-mediated Transport

Končekova, Jana; Kotorova, Klaudia; Gottlieb, Miroslav; Bona, Martin; Bonova, Petra

doi:10.1007/s11064-023-04002-x

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…The endogenous production of glutamate through metabolic pathways is very important in the brain, since the transport of circulating glutamate to brain normally plays only a minor role in regulating the brain glutamate levels. 41 The general decrease of NAD-GDH in different brain regions indicates that metabolism of glutamate by this reaction presumably increases the levels of glutamate during PTZ impact.…”

Section: Discussionmentioning

confidence: 99%

Pentylenetetrazole-Induced Seizures in Wistar Male Albino Rats with Reference to Glutamate Metabolism

Kanchi,

Meesala

2024

J Epilepsy Res

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Background and Purpose: Epilepsy is a common and heterogenous neurological disorder characterized by recurrent spontaneous seizures. Animal models like rats play a crucial role in finding of mechanism of epilepsy in different brain regions. i.e., cerebral cortex, cerebellum, hippocampus, and pons medulla. Glutamate is an important excitatory neurotransmitter in the central nervous system and also glutamate plays a vital role in neuronal development and memory. The process of neuronal death evolved by glutamate receptor activation, has been hypothesized in both acute and chronic degenerative disorders including epilepsy. Considering the multifactorial neurochemical and neurophysiological malfunctions consequent to epileptic seizures, a few antiepileptic drugs are designed, to mitigate the debilitating aspects of epilepsy.Methods: Rat model, pentylenetetrazole (PTZ), an anticonvulsant drug, was selected for the present study. Induction of epilepsy/convulsions was induced by an intraperitoneal injection of PTZ (60 mg/kg body weight) in saline. Biochemical assays performed through spectrophotometer.Results: Glutamine and Glutamine synthetase levels were decreased in the epileptic rats brain regions i.e., hippocampus, cerebellum, cerebral cortex, and pons medulla; glutamate dehydrogenase and glutaminase levels were increased in all the regions of epilepsy induced rats. Highest values are recorded in hippocampus when compared to other brain regions.Conclusion: PTZ suppresses the function of Glutamine and Glutamine synthetase activities in selected brain regions of rat and enhances the activities of the glutaminase and glutamate dehydrogenase when compared to control rats.

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Section: Discussionmentioning

confidence: 99%

Pentylenetetrazole-Induced Seizures in Wistar Male Albino Rats with Reference to Glutamate Metabolism

Kanchi,

Meesala

2024

J Epilepsy Res

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New alternative approaches to stroke treatment: the blood cell–derived secretome shows promise in individuals with obesity

Kotorová,

Končeková,

Bona

et al. 2024

Metab Brain Dis

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Ischaemic tolerance induced by remote ischaemic conditioning (RIC) has been extensively demonstrated in several preclinical models of cerebral ischaemia. However, animals with common stroke-related comorbidities do not benefit from the recent advances of RIC. Therefore, we investigated two alternative approaches for obese animals with stroke: (1) the efficacy of an additional round of the standard RIC protocol, and (2) the paracrine potential of the blood cell–derived secretome derived from RIC-induced healthy young rats. We found that a second round of remote ischaemic postconditioning (RIPostC) stimulus reduced neurodegeneration and exerted antioxidant effects but failed to decrease the infarct volume and alter glutamate homeostasis. However, when obese rats were administered the secretome from healthy, young RIC-stimulated rats, they exhibited improved neurological post-stroke outcomes. Intravenous administration of the tolerant secretome activated several endogenous mechanisms, including a reduction in the infarct volume and neurodegeneration in the penumbra. Furthermore, the blood cell–derived secretome accelerated brain-to-blood glutamate efflux in obese rats, and demonstrated antioxidant properties that may have contributed to the induction of tolerance in obese rats with stroke. These findings indicate that the blood cell–derived secretome has unique abilities and represents a new potential treatment for individuals with obesity and ischaemic stroke.

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Age affects the association of red blood cell indices with efficacy of remote ischemic conditioning in patients with acute moderate ischemic stroke

Wu,

Zhang,

Zhang

et al. 2024

Sci Rep

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We conducted a post hoc analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to investigate whether red blood cell (RBC) indices are associated with efficacy of remote ischemic conditioning (RIC), and whether the association is affected by age. In this post hoc analysis, patients with RBC indices at admission were enrolled. RBC indices including RBC count, hematocrit (HCT), mean corpuscular volume (MCV), hemoglobin (HB), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed. According to the median of these RBC indices, eligible patients were divided into high and low groups, which were further subdivided into RIC and control subgroups. Primary endpoint was excellent functional outcome defined as a modified Rankin Scale score of 0–1 at 90 days, which was used to evaluate RIC efficacy. RIC efficacy as well as effect of age on RIC efficacy were analyzed across the high and low groups of different RBC indices, and the interaction effects of RBC indices on RIC efficacy were evaluated. A total of 1640 patients were enrolled in the final analysis. In overall patients, no significant interaction effects of RIC intervention by all RBC indices were found, although there was a trend in interaction effect of RIC intervention by MCH (p = 0.116). However, we found an effect of age on the association of MCH with RIC efficacy. In patients over 60 years old, MCH significantly affected RIC efficacy (p = 0.006) and RIC significantly produced a higher proportion of primary outcome in high MCH (72.6% vs. 59.1%, P < 0.001) vs. low MCH group (61.2% vs. 62%, P = 0.829), which was not identified in patients under 60 years old. Furthermore, RIC efficacy decreased with increasing age in patients with low MCH with significant interaction effect (p = 0.012), while RIC efficacy increased with increasing age in patients with high MCH although no significant interaction (p = 0.126). No significant interaction effects of RIC intervention by RBC count, HCT, MCV, HB, and MCHC were found regardless of age. This secondary analysis of RICAMIS suggested that RIC exhibited more obvious benefit in AIS patients over 60 years old with high MCH compared with those with low MCH group, but RBC count, HCT, MCV, HB, and MCHC were not associated with the efficacy of RIC treatment regardless of age. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-74293-9.

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Remote Ischaemic Preconditioning Accelerates Brain to Blood Glutamate Efflux via EAATs-mediated Transport

Cited by 4 publications

References 38 publications

Pentylenetetrazole-Induced Seizures in Wistar Male Albino Rats with Reference to Glutamate Metabolism

Pentylenetetrazole-Induced Seizures in Wistar Male Albino Rats with Reference to Glutamate Metabolism

New alternative approaches to stroke treatment: the blood cell–derived secretome shows promise in individuals with obesity

Age affects the association of red blood cell indices with efficacy of remote ischemic conditioning in patients with acute moderate ischemic stroke

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