Anti-seizure efficacy of perampanel in two established rodent models of early-life epilepsy.

Early-life seizures can be refractory to conventional antiseizure medications (ASMs) and can also result in chronic epilepsy and long-term behavioral and cognitive deficits. Treatments targeting age-specific mechanisms contributing to epilepsy would be of clinical benefit. One such target is the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subtype of excitatory glutamate receptor, which is upregulated in the developing brain.

Altered hippocampal dendritic spine maturation after hypoxia-induced seizures in neonatal rats.

Cognitive comorbidities often follow early-life seizures (ELS), especially in the setting of autism and other neurodevelopmental syndromes. However, there is an incomplete understanding of whether neuronal and synaptic development are concomitantly dysregulated. We have previously shown that hypoxia-induced seizures (HS) in postnatal day (P)10 rats increase acute and later-life hippocampal glutamatergic neurotransmission and spontaneous recurrent seizures, and impair cognition and behavior.

Isotype-Switched Autoantibodies Are Necessary To Facilitate Central Nervous System Autoimmune Disease in and Mice.

B cell-depleting therapies have been shown to ameliorate symptoms in multiple sclerosis (MS) patients; however, the mechanism of action remains unclear. Following priming with Ag, B cells undergo secondary diversification of their BCR, including BCR class-switch recombination (CSR) and somatic hypermutation (SHM), with both processes requiring the enzyme activation-induced (cytidine) deaminase. We previously reported that activation-induced (cytidine) deaminase is required for full clinical manifestation of disease in an animal model of MS (experimental autoimmune encephalomyelitis; EAE) provoked by immunization with the extracellular domain of recombinant human myelin oligodendrocyte glycoprotein (hMOG).

Regulation of seizure-induced MeCP2 Ser421 phosphorylation in the developing brain.

Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of Ca1.2 L-type voltage gated calcium (Ca) channels (LT-VGCCs) and Ca-permeable AMPARs (CP-AMPARs) lacking GluA2 subunits.