Gestational deltamethrin exposure increases susceptibility to post-traumatic epilepsy in offspring and attenuates the alleviating effects of dietary curcumin

Epilepsy is a serious neurological disorder, and gestational exposure to deltamethrin (DLT), a commonly used insecticide, is increasingly suspected to contribute to its pathogenesis. This is particularly concerning as many pregnant individuals may encounter DLT-containing insecticides, potentially influencing epileptogenesis in their offspring. Although DLT typically does not cross the blood-brain barrier in adults, its lipophilic nature renders it neurotoxic during early brain development. Post-traumatic epilepsy (PTE), a prevalent form of epilepsy in children following traumatic brain injury (TBI), has been shown to be alleviated by curcumin in preclinical studies. In this study, pregnant rats were exposed to DLT during gestation, and PTE was induced in the offspring postnatally. Curcumin was administered orally to evaluate its neuroprotective potential. Experimental assessments included electrocorticography (ECoG), behavioral analysis, Golgi staining, immunofluorescence, and immunohistochemistry. Our findings reveal that gestational DLT exposure exacerbates seizure severity, reduces dendritic complexity, and upregulates sodium channel subunits NaV1.1 and NaV1.6 during epileptogenesis. Concurrently, synaptic markers PSD95 and synaptophysin (SYP) were downregulated, while astrocytic and microglial activation increased. Curcumin treatment attenuated neuronal hyperexcitability, restored dendritic arborization, and modulated the expression of sodium channels and synaptic proteins. However, prenatal DLT exposure diminished the therapeutic efficacy of curcumin. These results highlight the increased vulnerability to PTE following gestational DLT exposure and suggest that such exposure may impair the effectiveness of curcumin as an antiepileptic intervention.