Ongoing loss of viable neurons for weeks after mild perinatal hypoxia-ischemia.

Unlabelled: Mild hypoxic-ischemic encephalopathy is common in neonates with no evidence-based therapies, and 30-40% of patients experience adverse outcomes. The nature and progression of mild injury is poorly understood. Thus, we studied the evolution of mild perinatal brain injury using longitudinal two-photon imaging of transgenic fluorescent proteins as a novel readout of neuronal viability and activity at cellular resolution.

Displacement of extracellular chloride by immobile anionic constituents of the brain's extracellular matrix.

GABA is the primary inhibitory neurotransmitter. Membrane currents evoked by GABA receptor activation have uniquely small driving forces: their reversal potential (E) is very close to the resting membrane potential. As a consequence, GABA currents can flow in either direction, depending on both the membrane potential and the local intra and extracellular concentrations of the primary permeant ion, chloride (Cl).

WONOEP appraisal: Targeted therapy development for early onset epilepsies.

The early onset epilepsies encompass a heterogeneous group of disorders, some of which result in drug-resistant seizures, developmental delay, psychiatric comorbidities, and sudden death. Advancement in the widespread use of targeted gene panels as well as genome and exome sequencing has facilitated the identification of different causative genes in a subset of these patients. The ability to recognize the genetic basis of early onset epilepsies continues to improve, with de novo coding variants accounting for most of the genetic etiologies identified.

Neuronal Death: Now You See It, Now You Don't.

Fatally injured neurons may necrose and rupture immediately, or they may initiate a programmed cell death pathway and then wait for microglial phagocytosis. Biochemical and histopathologic assays of neuronal death assess the numbers of neurons awaiting phagocytosis at a particular time point after injury. This number varies with the fraction of neurons that have necrosed vs initiated programmed cell death, the time elapsed since injury, the rate of phagocytosis, and the assay's ability to detect neurons at different stages of programmed cell death.

Timing of interventions to control neuronal chloride elevation in a model of neonatal seizures after hippocampal injury.

Objective: Following hypoxic-ischemic (HI) brain injury, neuronal cytoplasmic chloride concentration ([Cl]) increases, potentially contributing to depolarizing γ-aminobutyric acid (GABA) responses, onset of seizures, and the failure of antiepileptic drugs that target inhibitory chloride-permeable GABA receptors. Post-HI seizures characteristically begin hours after injury, by which time substantial accumulation of [Cl] may have already occurred. In immature neurons, a major pathway for Cl influx is the reversible Na-K-2Cl cotransporter NKCC1.