Open AccessNeuroprotective effects of deep hypothermia in refractory status epilepticus
Author(s) -
Niquet Jerome,
Gezalian Michael,
Baldwin Roger,
Wasterlain Claude G.
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.262
Subject(s) - medicine , status epilepticus , hypothermia , dentate gyrus , neuroprotection , anesthesia , hippocampus , neocortex , pharmacology , epilepsy , psychiatry
Objective Pharmacoresistance develops quickly during repetitive seizures, and refractory status epilepticus ( RSE ) remains a therapeutic challenge. The outcome of RSE is poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (20°C) is used clinically during reconstructive cardiac surgery and neurosurgery, and has proved safe and effective in those indications. We tested the hypothesis that deep hypothermia reduces RSE and its long‐term consequences. Methods We used a model of SE induced by lithium and pilocarpine and refractory to midazolam. Several EEG measures were recorded in both hypothermic ( n = 17) and normothermic ( n = 20) animals. Neuronal injury (by Fluoro‐Jade B), cell‐mediated inflammation, and breakdown of the blood–brain barrier (BBB) (by immunohistochemistry) were studied 48 h following SE onset. Results Normothermic rats in RSE seized for 4.1 ± 1.1 h, and at 48 h they displayed extensive neuronal injury in many brain regions, including hippocampus, dentate gyrus, amygdala, entorhinal and pyriform cortices, thalamus, caudate/putamen, and the frontoparietal neocortex. Deep hypothermia (20°C) of 30 min duration terminated RSE within 12 min of initiation of hypothermia, reduced EEG power and seizure activity upon rewarming, and eliminated SE ‐induced neuronal injury in most animals. Normothermic rats showed widespread breakdown of the BBB, and extensive macrophage infiltration in areas of neuronal injury, which were completely absent in animals treated with hypothermia. Interpretation These results suggest that deep hypothermia may open a new therapeutic avenue for the treatment of RSE and for the prevention of its long‐term consequences.