Diisopropylfluorophosphate-induced status epilepticus drives complex glial cell phenotypes in adult male mice

Neuroinflammation as a Therapeutic Target for Mitigating the Long-Term Consequences of Acute Organophosphate Intoxication

“…Experimental findings suggest that initial astrocytic responses are neuroprotective, whereas a second "wave" of activation in the first few days post-SE promotes acute neurodegeneration (Lazar et al, 2016). Consistent with these observations, a recent functional characterization of astrocytic responses in a mouse model of acute DFP intoxication suggested that neurotoxic "A1" astrocytes emerge several days post-SE (Maupu et al, 2021). Specific functional subsets of astrocytes have not been targeted by therapeutic intervention; therefore, the relative contributions of A1 vs. A2 astrocytes to the neurologic sequelae of SE induced by OPs or other chemicals remain in question.…”

“…These data suggest that the functional profile of microglia similarly changes with time following acute OP intoxication. Consistent with this possibility, temporal shifts in microglial phenotype are observed in non-OP models of SE ( Benson et al, 2015 ), and evidence from a mouse model of acute DFP intoxication hints at similar changes in microglial phenotype during the first several days following DFP-induced SE ( Maupu et al, 2021 ). More research is needed to fully characterize the spatiotemporal profile of microglial polarization over more extended periods of time after acute OP intoxication and to determine the effects of interventions targeting functional subsets of microglia on long-term neurologic consequences.…”

“…This schematic presents one model of the functional polarization of microglia and astrocytes following acute OP intoxication illustrating a continuum from the extreme pro-inflammatory to anti-inflammatory state. There is some evidence of phenotypic diversity of microglia and astrocytes in animal models of acute OP intoxication ( Maupu et al, 2021 ). Figure created with BioRender.com .…”

“…Thus, in situations with robust and potentially shifting profiles of microglial activation, it is likely that the functional polarization of microglia critically influences the functional polarization of astrocytes, and ultimately, the general direction of the neuroinflammatory response following acute OP intoxication. Indeed, there is evidence that neurotoxic C3-positive astrocyte polarization develops by 3 days after kainate- or DFP-induced SE ( Wei et al, 2020 ; Maupu et al, 2021 ) and remains elevated at 6 weeks post intoxication ( Putra et al, 2020 ). Importantly, this astrocytic polarization was dependent on microglial function ( Wei et al, 2020 ), suggesting that microglia promoted the delayed development of neurotoxic astrocytes following acute OP intoxication.…”

Neuroinflammation and Modulation Role of Natural Products After Spinal Cord Injury

“…63 By analogy with M1 and M2 macrophages/microglia, two phenotypes of reactive astrocytes are defined as A1 and A2. 64,65 A1 astrocytes possess a neurotoxic effect and participate in the pathogenesis of multiple neurologic diseases. In contrast, A2 astrocytes are suggested to display a neuroprotective effect.…”