Mild passive focal cooling prevents epileptic seizures after head injury in rats

Raimondo D'Ambrosio, Clifford L. Eastman, Felix Darvas, Jason S. Fender, Derek R. Verley, Federico M. Farin, Hui Wen Wilkerson, Nancy R. Temkin, John W. Miller, Jeffrey Ojemann, Steven M. Rothman, Matthew D. Smyth

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Objective Post-traumatic epilepsy is prevalent, often difficult to manage, and currently cannot be prevented. Although 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. Methods 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 to 16 weeks postinjury. Focal cooling was induced with ECoG headsets engineered for calibrated passive heat dissipation. Pathophysiology was assessed by glial fibrillary acidic protein immunostaining, cortical sclerosis, gene expression of inflammatory cytokines interleukin (IL)-1α and IL-1β, and ECoG spectral analysis. All animals were formally randomized to treatment groups, and data were analyzed blind. Results Cooling by 0.5 to 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, >10 weeks after cessation of cooling. Rare remaining seizures were shorter than in controls. Interpretation 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. ANN NEUROL 2013;73:199-209

Original languageEnglish
Pages (from-to)199-209
Number of pages11
JournalAnnals of neurology
Volume73
Issue number2
DOIs
StatePublished - Feb 2013

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