Mild passive focal cooling prevents epileptic seizures after head injury in rats.
Mild passive focal cooling prevents epileptic seizures after head injury in rats.
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DOI：
10.1002/ana.23764
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发表时间：
2013-02
影响因子：
11.2
通讯作者：
Smyth, Matthew D.
中科院分区：
文献类型：
--
作者：
D'Ambrosio, Raimondo;Eastman, Clifford L.;Darvas, Felix;Fender, Jason S.;Verley, Derek R.;Farin, Federico M.;Wilkerson, Hui-Wen;Temkin, Nancy R.;Miller, John W.;Ojemann, Jeffrey;Rothman, Steven M.;Smyth, Matthew D.
Posttraumatic epilepsy is prevalent, often difficult to manage, and currently cannot be prevented. While cooling is broadly neuroprotective, cooling-induced prevention of chronic spontaneous recurrent seizures has never been demonstrated. We examined the effect of mild passive focal cooling of the perilesional neocortex on the development of neocortical epileptic seizures after head injury in the rat. Rostral parasagittal fluid percussion injury in rats reliably induces a perilesional, neocortical epileptic focus within weeks after injury. Epileptic seizures were assessed by 5-electrode video-electrocorticography (ECoG) 2–16 weeks post-injury. Focal cooling was induced with ECoG headsets engineered for calibrated passive heat dissipation. Pathophysiology was assessed by GFAP immunostaining, cortical sclerosis, gene expression of inflammatory cytokines IL-1α and IL-1β, and ECoG spectral analysis. All animals were formally randomized to treatment groups and data were analyzed blind. Cooling by 0.5–2°C inhibited the onset of epileptic seizures in a dose dependent fashion. The treatment induced no additional pathology or inflammation, and normalized the power spectrum of stage N2 sleep. Cooling by 2°C for 5.5 weeks beginning 3 days after injury virtually abolished ictal activity. This effect persisted through the end of the study, over ten weeks after cessation of cooling. Rare remaining seizures were shorter than in controls. These findings demonstrate potent and persistent prevention and modification of epileptic seizures after head injury with a cooling protocol that is neuroprotective, compatible with the care of head-injury patients, and conveniently implemented. The required cooling can be delivered passively without Peltier cells or electrical power.
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