Prolonged prophylactic effects of gabapentin on status epilepticus-induced neocortical injury

NEUROBIOLOGY OF DISEASE

卷:142

Article

Perez-Ramirez, Maria-Belen¹  Gu, Feng¹  Prince, David A.¹ 

[1] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA

关键词: Focal neocortical SE;    Epileptogenesis;    Neuronal injury;    Gliosis;    Aberrant hyperexcitability;    SE prophylaxis;   

DOI  :  10.1016/j.nbd.2020.104949

来源: Elsevier

【 摘 要 】

Long-term consequences of status epilepticus (SE) occur in a significant proportion of those who survive the acute episode. We developed an in vivo model of acute focal neocortical SE (FSE) to study long-term effects on local cortical structure and function and potential strategies to mitigate adverse consequences of SE. An acute 2 h episode of FSE was induced in anesthetized mice by epidural application of gabazine +4-aminopyridine over sensorimotor neocortex. Ten and 30 days later, the morphological and functional consequences of this single episode of FSE were studied using immunocytochemical and electrophysiological techniques. Results, focused on cortical layer V, showed astrogliosis, microgliosis, decreased neuronal density, and increased excitatory synapses, along with increased immunoreactivity for thrombospondin 2 (TSP2) and a2d-1 proteins. In addition, neocortical slices, obtained from the area of prior focal seizure activity, showed abnormal epileptiform burst discharges along with increases in the frequency of miniature and spontaneous excitatory postsynaptic currents in layer V pyramidal cells, together with decreases in both parvalbumin immunoreactivity (PV-IR) and the frequency of miniature inhibitory postsynaptic currents in layer V pyramidal cells. Treatment with an approved drug, gabapentin (GBP) (ip 100 mg/kg/day 3x/day for 7 days following the FSE episode), prevented the gliosis, the enhanced TSP2- and alpha 2 delta-1- IR and the increased excitatory synaptic density in the affected neocortex. This model provides an approach for assessing adverse effects of FSE on neocortical structure and function and potential prophylactic treatments.