Gestational deltamethrin exposure exacerbates post-traumatic epileptiform activity and social deficits, diminishing the therapeutic efficacy of curcumin in rats.

Gestational exposure to the neurotoxic insecticide deltamethrin (DLT) is suspected to increase susceptibility to neurological disorders, but its impact on secondary brain injuries and therapeutic interventions remains poorly understood. This study investigates whether prenatal DLT exposure exacerbates post-traumatic epileptogenesis in offspring and evaluates whether it compromises the neuroprotective efficacy of curcumin. Pregnant rats were exposed to DLT during gestation, and post-traumatic epileptiform activity was subsequently induced in the offspring using a focal FeCl₃ cortical injury model. Following oral curcumin administration, subjects were evaluated utilizing electrocorticography, behavioral assays, Golgi staining, and immunohistochemistry. We found that gestational DLT exposure significantly exacerbated injury pathology, evidenced by heightened neuronal hyperexcitability, severe social behavioral deficits, reduced dendritic complexity, profound loss of synaptic markers (PSD95 and SYP), upregulation of voltage-gated sodium channels (NaV1.1 and NaV1.6), and aggravated glial activation. Crucially, while curcumin treatment successfully attenuated molecular, histological, and electrophysiological pathologies, prior DLT exposure exacerbated the epileptic phenotype and severely interfered with curcumin's overall therapeutic efficacy, preventing absolute cellular markers from fully returning to unexposed recovery levels. Furthermore, prior DLT exposure actively blunted curcumin's ability to rescue complex social behavioral deficits. These findings demonstrate that early-life environmental toxicant exposure increases vulnerability to post-traumatic epileptogenesis and establishes a severely aggravated pathological baseline that limits the overall restorative capacity of subsequent interventions.