EVALUATING THE ELECTROPHYSIOLOGICAL SIGNATURES OF INFANTILE SPASMS IN A MODEL OF NEONATAL HYPOXIA

Infantile Spasms (IS) are a rare condition occurring in infancy, characterised by epileptic spasms, developmental regression, and electroencephalographic abnormalities including hypsarrhythmia. Although rare (1.6–4.5 cases per 10,000 births), its presentation (3-7 months of age) poses a risk of neurodevelopment impairment, with many cases being treatment resistant. The pathophysiology remains unclear, and pre-clinical models rarely capture the phenotype. Hypoxic-ischemic encephalopathy (HIE) is an associated aetiology, but its contribution to IS-relevant neuronal network dysfunction remains poorly understood. To define the pathophysiological signature of IS, we developed an ex vivo electrophysiological model in hypoxic mice. Neonatal hypoxia was induced in C57BL/6J mice on postnatal day 7 (P7), and somatosensory cortex slices (400μm) were prepared for local field potential recordings at P10, P12, and P14, alongside age-matched controls. To induce slow-wave activity relevant to hypsarrhythmia-like patterns, we applied the cholinergic agonist carbachol (2μM) and the D₁ receptor antagonist SCH23390 (10μM), followed by corticotrophin-releasing factor (CRF) (20nM), a factor implicated in neonatal seizure susceptibility. At baseline, hypoxia slices showed increased delta-band (0.5-4Hz) power with area under the curve (AUC) and maximal event amplitude increased by 2–3-fold compared to controls. CRF increased network activity across ages, with hypoxia slices exhibiting greater increases in AUC and maximal amplitude, alongside increased event variability, particularly at P10–P12. Post-hypoxia behavioural assessment indicated deficits in motor and sensorimotor performance. Together, these findings support the development of an HIE-relevant ex vivo model of IS-like network activity for future mechanistic and pharmacological studies.