RT Journal Article
T1 Inhibition of Astrocyte Reactivity by Mdivi-1 After Status Epilepticus in Rats Exacerbates Microglia-Mediated Neuroinflammation and Impairs Limbic–Cortical Glucose Metabolism
A1 Gómez Oliver, Francisca
A1 Fernández de La Rosa, Rubén
A1 Brackhan, Mirjam
A1 Bascuñana, Pablo
A1 Pozo García, Miguel Ángel
A1 García García, Luis
AB 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.
PB MDPI
YR 2025
FD 2025-08-27
LK https://hdl.handle.net/20.500.14352/124172
UL https://hdl.handle.net/20.500.14352/124172
LA eng
NO 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
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 18 dic 2025