Biology subjects

Roumes, H.

Publications and source records attributed to Roumes, H..

3 recordsLinked to original sources

bioRxiv2026

Lactate Promotes an Anti-Inflammatory Phenotype in Activated Microglia

Microglial activation is a central component of neuroinflammatory responses in many brain pathologies. Increasing evidence indicates that microglial phenotype is tightly linked to cellular metabolism, with pro-inflammatory activation associated with enhanced glycolytic flux. Lactate, traditionally considered a metabolic substrate, has recently emerged as a signaling molecule capable of modulating immune responses. However, its direct impact on microglial inflammatory activation remains incompletely understood. In the present study, we investigated the effects of lactate on microglial phenotype under inflammatory conditions using primary rat microglial cultures stimulated with lipopolysaccharide (LPS). Microglial activation was assessed through the expression of phenotypic markers, cytokine production, and secreted chemokine profiles. LPS stimulation induced a strong pro-inflammatory response characterized by increased CD86 expression, elevated TNF-alpha secretion, and enhanced release of several pro-inflammatory chemokines. Post-treatment with sodium L-lactate significantly attenuated these inflammatory responses, reducing pro-inflammatory marker expression and cytokine secretion, while restoring the anti-inflammatory marker CD206. To explore the relevance of these findings in a pathological context, the effects of lactate were further examined in a neonatal rat model of hypoxia-ischemia. Sodium L-lactate administration after injury reduced microglial activation and promoted a shift toward an anti-inflammatory phenotype in cortical regions, whereas hippocampal microglia showed a more limited response. Together, these results demonstrate that lactate directly modulates microglial inflammatory activation and cytokine production in vitro and suggest that lactate-mediated metabolic signaling may contribute in vivo to the regulation of neuroinflammatory responses.

neuroscience↗

bioRxiv2026

A Grape Seed Oligomeric Procyanidin Extract Reverses Diet-Induced Obesity Through Gut Microbiota Remodeling and Restoration of GLP-1, Gut-Brain, and Gut-Liver Signaling

BackgroundObesity is a complex multifactorial disease associated with chronic low grade inflammation, gut microbiota dysbiosis, and impaired gut-brain communication. Oligomeric procyanidins from grape seed extracts (GSE) are promising prebiotic candidates, capable of modulating host metabolism through interactions with the gut microbiota. MethodsC57Bl/6J male mice were rendered obese by feeding them a high fat, high sucrose diet and were orally administered GSE at a dose of 1or 2 g/kg/day for 12 weeks. We assessed body weight, adiposity, glucose tolerance, insulin sensitivity, circulating hormones, brain homeostasis markers, colonic and liver gene expression, 16S rRNA gene sequencing of the gut microbiota profiles, and untargeted cecal metabolomics. ResultsGSE reduced body weight gain, visceral adiposity, adipocyte hypertrophy, and improved oral glucose tolerance and insulin sensitivity. It normalized circulating lipid and glucose levels and lowered fasting insulin and leptin while increasing endogenous GLP-1. Hepatic gene expression analysis revealed a dose-dependent restoration of antioxidant defenses (SOD, CAT) and lipogenic transcription factors (SREBP, ChREBP). In the colon, GSE attenuated pro-inflammatory IL6 cytokine expression and strikingly upregulated GLP-1 and GLP-1 receptor expression. Microbiota analysis revealed a profound, dose-dependent remodeling of gut microbiota composition and diversity, with an expansion of health-associated taxa, such as Akkermansia muciniphila. Brain analyses revealed restoration of NAA and BDNF levels together with markers consistent with improved mitochondrial function. Cecal metabolomics revealed normalization of secondary bile acid metabolism, restoration of arginine bioavailability, and reduction in the accumulation of L-DOPA and spermidine. ConclusionsAn oligomeric procyanidin-rich grape seed extract acts as a multitarget prebiotic that alleviates diet-induced obesity and is associated with coordinated restoration of gut microbiota composition, GLP-1 signaling, and gut-brain and gut-liver communication pathways. Convergent dose-dependent effects on Akkermansia muciniphila abundance, GLP-1, NAA, and BDNF identify key mechanisms underlying its metabolic benefits.

microbiology↗

bioRxiv2026

Optimizing therapeutic hypothermia conditions in a translational preclinical model of neonatal hypoxia-ischemia in rats

BackgroundTherapeutic hypothermia is the only clinically approved treatment for neonatal hypoxia-ischemia (NHI), although its efficacy remains partial. In preclinical research, hypothermia is widely used as a reference therapy; however, its protocol is highly variable across studies, limiting robust comparisons with emerging neuroprotective strategies. This study aimed to define an optimal and standardized hypothermia protocol in the Rice-Vannucci model, not to challenge clinical practice, but to establish a reliable benchmark for preclinical therapeutic development. MethodsNHI was induced in postnatal day 7 (P7) rat pups, followed by normothermia or hypothermia for 2, 3, or 5 hours. Short- and long-term outcomes were assessed using lesion volume measurements by MRI, neurological scoring, behavioral tests, and histological analyses. The impact of immediate hypothermia initiation was also examined. ResultsAcross analyses, both 2- and 3-hour hypothermia durations provided greater neuroprotection than 5 hours--including brain lesion volume, motor and cognitive performances, and markers of neuronal preservation and neuroinflammation. However, for several parameters, 2 hours of hypothermia showed superior efficacy compared with 3 hours. Immediate initiation further modestly improved outcomes. ConclusionA 2-hour hypothermia protocol represents the most robust and reproducible preclinical reference, enabling meaningful comparison with novel therapies in the Rice-Vannucci model. IMPACTO_LIBy establishing an optimized hypothermia protocol in the Rice-Vannucci model, this study offers a consistent and robust reference for preclinical evaluation of emerging therapies. C_LIO_LIIt does not question clinical hypothermia protocols, but addresses variability in preclinical literature C_LIO_LIOptimizing the hypothermia reference protocol is mandatory to reliably identify new effective treatments in preclinical studies and to enhance their likelihood of successful and efficient clinical translation C_LI

neuroscience↗