2026-06-28T14:58:27Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1241722025-09-23T00:15:46Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Gómez Oliver, Francisca author Fernández de La Rosa, Rubén author Brackhan, Mirjam author Bascuñana, Pablo author Pozo García, Miguel Ángel author García García, Luis 2025-09-22T07:23:12Z 2025-09-22T07:23:12Z 2025-08-27 Gómez-Oliver, F., Fernández de la Rosa, R., Brackhan, M., Bascuñana, P., Pozo, M. Á., & García-García, L. (2025). Inhibition of Astrocyte Reactivity by Mdivi-1 After Status Epilepticus in Rats Exacerbates Microglia-Mediated Neuroinflammation and Impairs Limbic–Cortical Glucose Metabolism. Biomolecules, 15(9), 1242. https://doi.org/10.3390/biom15091242 10.3390/biom15091242 https://hdl.handle.net/20.500.14352/124172 2218-273X https://doi.org/10.3390/biom15091242 https://www.mdpi.com/2218-273X/15/9/1242 The lithium–pilocarpine rat model of status epilepticus (SE) is a well-established paradigm for studying epileptogenesis. Astrocyte reactivity has been implicated in modulating seizure susceptibility and neuroinflammation, yet its functional role in early epileptogenesis remains unclear. Herein, we evaluated the effects of Mdivi-1, a pharmacological inhibitor of mitochondrial fission protein Drp1, for its ability to modulate astrocytic mitochondrial dynamics and for its reported preventive neuroprotective properties. Mdivi-1 was administered shortly after SE onset, and we assessed brain glucose metabolism using [18F]FDG PET, alongside histological markers of neurodegeneration, astrocyte reactivity, and microglial activation, at 3 days post-SE. As expected, SE induced widespread brain hypometabolism measured by a VOI analysis, hippocampal neurodegeneration, and glial activation. Post-SE Mdivi-1 administration reduced hippocampal astrogliosis but neither conferred neuroprotection nor rescued glucose metabolism. On the contrary, Mdivi-1 exacerbated limbic–cortical hypometabolism when evaluated by SPM and normalized to whole brain tracer uptake and microglia-mediated neuroinflammation. These findings challenge the assumption that early astrocyte inhibition confers neuroprotection. Furthermore, early suppression of astrocyte reactivity after the damage has occurred may shift the neuroinflammatory response toward maladaptive microglial activation. Thus, while Mdivi-1 holds promise as a preventive neuroprotective agent, its use post-SE may have unintended adverse effects on the brain’s response to SE. eng Attribution 4.0 International Inhibition of Astrocyte Reactivity by Mdivi-1 After Status Epilepticus in Rats Exacerbates Microglia-Mediated Neuroinflammation and Impairs Limbic–Cortical Glucose Metabolism journal article 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URL https://docta.ucm.es/bitstreams/8c8b9826-b32f-4c8a-a3d3-94583ec9e2af/download File MD5 15d6051bc44d97d9a8608e90fa8038a2 4155268 application/pdf Inhibition of Astrocyte Reactivity.pdf