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Activation in the amygdala and associated structures. Horizontal sections at bregma −4.28 mm showing TdT‐labeled cells (red) and ChAT‐labeled cells (green) and merged images of a mouse with a grade 2 behavioral seizure (top panel) and a control mouse (bottom panel). Regions marked are Acb, nucleus accumbens; BLA, basolateral amygdaloid nucleus; BNST, bed nucleus of the stria terminalis; CeM, central amygdaloid nucleus; CPu, striatum; GP, globus pallidus; La, lateral amygdaloid nucleus; nbM, nucleus basalis of Meynert; PH, posterior hypothalamic nucleus
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Objective
Patients with temporal lobe epilepsy (TLE) frequently report debilitating comorbidities such as memory impairments, anxiety, and depression. An extensive neuronal network generates epileptic seizures and associated comorbidities, but a detailed description of this network is unavailable, which requires the generation of neuronal activatio...
Citations
... Our results also confirmed that seizure intensity is not related to neurodegeneration. Instead, DFP-exposed male rats showed more neurodegeneration in the somatosensory cortex, consistent with a recent study that reported a positive correlation between seizure severity and increased involvement of cortical regions (Dabrowska et al., 2019;Singh et al., 2020Singh et al., , 2022Adotevi and Kapur, 2022). Clinical studies also suggested that cortical structures involved in focal hippocampal seizures contribute to the manifestation of more severe convulsions in patients with epilepsy (Kwan and Brodie, 2000;Bragin et al., 2005). ...
Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure are unclear. The organophosphate (OP), diisopropylfluorophosphate (DFP), is known to cause neurotoxicity and status epilepticus (SE), a serious neurologic condition that causes prolonged seizures and brain damage. Current therapies for OP poisoning and SE do not consider neuronal variations between male and female brains. Therefore, we investigated sex-dependent differences in electrographic seizure activity and neuronal injury using the DFP model of refractory SE in rats. EEG recordings were used to monitor DFP-induced SE, and the extent of brain injury was determined using fluoro-jade-B staining to detect cellular necrosis. After DFP exposure, we observed striking sex-dependent differences in SE and seizure activity patterns as well as protective responses to midazolam treatment. Following acute DFP exposure, male animals displayed more severe SE with intense epileptiform spiking and greater mortality than females. In contrast, we observed significantly more injured cells and cellular necrosis in the hippocampus and other brain regions in females than in males. We also observed extensive neuronal injury in the somatosensory cortex of males. The anticonvulsant effect of midazolam against SE was limited and found to be similar in males and females. However, unlike males, females exhibited substantially more protection against neuronal damage after midazolam treatment. Overall, these results demonstrate significant sex-dependent differences in DFP-induced refractory SE and neuronal damage, suggesting that it may be possible to develop sex-specific neuroprotective strategies for OP intoxication and refractory SE. Significance Statement Sex-dependent differences in neurotoxicity and SE are key biological variables after OP exposure. Here, we investigated sex-dependent differences in SE and brain injury after acute DFP exposure. Male rats had more severe SE and less survival than females, while females had more neuronal damage. Females had more neuroprotection to midazolam than males, while both sexes had similar but partial anticonvulsant effects. These findings suggest that a sex-specific therapeutic approach may prevent neurological complications of OP-induced SE.
