Targeting ischemia-induced KCC2 hypofunction rescues refractory neonatal seizures and mitigates epileptogenesis in a mouse model.

ABSTRACT: Neonatal seizures pose a clinical challenge in their early detection, acute management, and long-term comorbidities. They are often caused by hypoxic-ischemic encephalopathy and are frequently refractory to the first-line antiseizure medication phenobarbital. One proposed mechanism for phenobarbital inefficacy during neonatal seizures is the reduced abundance and function of the neuron-specific K⁺/Cl⁻ cotransporter 2 (KCC2), which maintains chloride homeostasis and promotes GABAergic inhibition upon its phosphorylation during postnatal development. Here, we investigated whether this mechanism is causal and whether it can be rescued by KCC2 functional enhancement. In a CD-1 mouse model of refractory ischemic neonatal seizures, treatment with the KCC2 functional enhance

SUBMITTER: Sullivan BJ 

PROVIDER: S-EPMC8763016 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature