From systemic to selective brain cooling – Methods in review

Therapeutic hypothermia (TH) remains one of the few proven neuroprotective modalities available in clinical practice today. Although targeting lower temperatures during TH seems to benefit ischemic brain cells, systemic side effects associated with global hypothermia limit its clinical applicability. Therefore, the ability to selectively reduce the temperature of the brain while minimally impacting core temperature allows for maximizing neurological benefit over systemic complications. In that scenario, selective brain cooling (SBC) has emerged as a promising modality of TH. In this report, we reviewed the general concepts of TH, from systemic to selective brain hypothermia, and explored the different cooling strategies and respective evidence, including preclinical and clinical data. SBC has been investigated in different animal models with promising results, wherein organ-specific, rapid, and deep target brain temperature managements stand out as major advantages over systemic TH. Nevertheless, procedure-related complications and adverse events still remain a concern, limiting clinical translation. Different invasive and noninvasive methods for SBC have been clinically investigated with variable results, and although adverse effects were still reported in some studies, therapies rendered overall safe profiles. Further study is needed to define the optimal technique, timing of initiation, rate and length of cooling as well as target temperature and rewarming protocols for different indications.