Recent antiepileptic and neuroprotective applications of brain cooling

Abstract

Hypothermia is a widely used clinical practice for neuroprotection and is a well-established method to mitigate the adverse effects of some clinical conditions such as reperfusion injury after cardiac arrest and hypoxic ischemic encephalopathy in newborns. The discovery, that lowering the core temperature has a therapeutic potential dates back to the early 20th century, but the underlying mechanisms are actively researched, even today. Especially, in the area of neural disorders such as epilepsy and traumatic brain injury, cooling has promising prospects. It is well documented in animal models, that the application of focal brain cooling can effectively terminate epileptic discharges. There is, however, limited data regarding human clinical trials. In this review article, we will discuss the main aspects of therapeutic hypothermia focusing on its use in treating epilepsy. The various experimental approaches and device concepts for focal brain cooling are presented and their potential for controlling and suppressing seizure activity are compared.

Cytostatic hypothermia and its impact on glioblastoma and survival

“…In those situations, gradual cooling effectively avoided seizure induction. The mechanism behind this is unknown as cooling is wellestablished to suppress seizures 45 but may be due to inhibition of GABA circuits that can be corrected with medication 46 . Other adverse effects of hypothermia are possible via reduced neural firing and cellular swelling but may be solved by gradually adjusting temperature, intermittent hypothermia, administering molecular inhibitors [30][31][32] , and the use of adjuvants to reduce the total length of therapy.…”

Focal Cooling for Drug-Resistant Epilepsy

“…For long-term implantation, a surface thermoelectric device such as a Peltier chip would seem most likely to be successful . A Peltier chip creates a temperature gradient between 2 different conductors when met with an electric current . These chips can be as small as 1.5 mm thick and a few millimeters in length and width and can reliably reduce the temperature of brain tissue immediately adjacent to them .…”

“…A Peltier chip creates a temperature gradient between 2 different conductors when met with an electric current . These chips can be as small as 1.5 mm thick and a few millimeters in length and width and can reliably reduce the temperature of brain tissue immediately adjacent to them . While Peltier chips are effective at reducing the temperature surrounding them, to act as an effective focal cooling device for DRE they must displace the resulting heat far from the epileptogenic cortex.…”

Using focal cooling to link neural dynamics and behavior

“…Given the utility of focal cooling in model systems, we have recently taken the first steps toward applying this perturbation approach toward investigating the link between brain function and behavior in human participants. Although cooling was previously used as a therapeutic approach for addressing conditions such as hypoxia or epilepsy (Csernyus et al, 2020), the application of focal cooling to understand brain function has been (C) Simple model of a hierarchically organized timing circuit. A recurrent neural network (top) produces an output that switches between a low and a persistent high level, which serves as input drive to a pattern-generating circuit (bottom) that produces bursts during the time the input is at a high level.…”