West syndrome, an age-specific epileptic
encephalopathy, manifests with
infantile spasms (IS) and impaired neurodevelopmental outcomes and
epilepsy. The multiple-hit rat model of IS is a chronic model of IS due to structural etiology, in which
spasms respond partially to
vigabatrin analogs. Using this model, we investigated whether IS due to structural etiology may have deficits in
parvalbumin (PRV) and
somatostatin (SST) immunoreactive (-ir) interneurons, and
calretinin-ir (CR-ir) neurons of the primary somatosensory cortex of postnatal day (PN) 20-24 rats, using specific immunohistochemical assays. PN3 Sprague-Dawley male rats underwent the multiple-hit induction protocol, were monitored until PN20-24, and were transcardially perfused to collect brains for histology. Age-matched
sham and naive control male rats were also used. Coronal brain cryosections were stained with anti-PRV, anti-CR, and anti-SST
antibodies, and regions of interest (ROIs) from the primary somatosensory cortices were selected to determine PRV-, CR-, and SST-ir cell counts and cortical ROI volumes, with blinding to experimental group. Statistical analyses were done using a linear mixed model accounting for repeated measures. We found PRV-ir interneuronal selective reduction, sparing of the CR-ir and SST-ir neurons, and bilateral cortical
atrophy. Our findings provide evidence for acquired PRV-selective interneuronopathy, possibly underlying the pathogenesis of IS, neurodevelopmental deficits, and
epilepsy, and potentially contributing to the partial response to
vigabatrin analogs in this model.