Epidural focal brain cooling abolishes neocortical seizures in cats and non-human primates

Neurosci Res. 2017 Sep;122:35-44. doi: 10.1016/j.neures.2017.04.007. Epub 2017 Apr 24.

Abstract

Focal brain cooling (FBC) is under investigation in preclinical trials of intractable epilepsy (IE), including status epilepticus (SE). This method has been studied in rodents as a possible treatment for epileptic disorders, but more evidence from large animal studies is required. To provide evidence that FBC is a safe and effective therapy for IE, we investigated if FBC using a titanium cooling plate can reduce or terminate focal neocortical seizures without having a significant impact on brain tissue. Two cats and two macaque monkeys were chronically implanted with an epidural FBC device over the somatosensory and motor cortex. Penicillin G was delivered via the intracranial cannula for induction of local seizures. Repetitive FBC was performed using a cooling device implanted for a medium-term period (FBC for 30min at least twice every week; 3 months total) in three of the four animals. The animals exhibited seizures with repetitive epileptiform discharges (EDs) after administration of penicillin G, and these discharges decreased at less than 20°C cooling with no adverse histological effects. The results of this study suggest that epidural FBC is a safe and effective potential treatment for IE and SE.

Keywords: Epilepsy; Focal brain cooling; Hypothermia; Implantable device; Motor cortex; Neuromodulation; Penicillin G.

MeSH terms

  • Animals
  • Cats
  • Disease Models, Animal
  • Electrocorticography
  • Epilepsy / chemically induced
  • Epilepsy / physiopathology
  • Epilepsy / therapy*
  • Female
  • Hypothermia, Induced* / adverse effects
  • Hypothermia, Induced* / instrumentation
  • Hypothermia, Induced* / methods
  • Macaca
  • Male
  • Motor Cortex / physiopathology*