The mechanisms by which cooling act to protect brain function remain largely speculative. Many aspects of acute, subacute and chronic stages of ischaemia appear to undergo modulation by cooling. It affects pathways leading to excitotoxicity, apoptosis (cell death in response to circumstance), inflammation and free radical production, as well as blood flow, metabolism and blood/brain barrier integrity. Hypothermia may also influence neurogenesis, gliogenesis and angiogenesis (recovery of brain, brain structure and blood vessel cells) after hypoxic injury.
It is believed that the underlying mechanisms involve multiple cellular and molecular pathways and that therapeutic hypothermia is predominantly neuroprotective in attenuating secondary injury after the initial damage caused by the arrest of perfusion. In its most simple understanding it is known that a reduction in temperature leads to a decrease in metabolism, thereby reducing the brain’s oxygen demands. It has been shown that a reduction of just 1ºC in body temperature reduces the cerebral metabolic rate by 6-7%. It is also believed that the treatment reduces the production of neurotransmitters like glutamate, as well as reducing free radicals that might damage the brain. The treatment may also help to mitigate the effects of a cytokine cascade and reduces the potential for fever which often develops in the hours following a major insult.
It has been postulated that the neuroprotective aspects of therapeutic hypothermia may be separate and distinct in each phase of recovery with cooling having some beneficial effect upon the heart in the intra-arrest, pre-ROSC phase; upon ischemia induced cell injury during reperfusion, particularly on free radical release in the few minutes following reperfusion; and in preventing cell death and inflammation in the recovery phase. This would help to explain the limited success clinical groups have had in translating the beneficial effects of early hypothermia on animals in arrest to human clinical trials and emphasises the importance of a study on pre-ROSC cooling and a seamless hypothermia protocol – cooling patients immediately upon collapse right through the recovery period.
In addition to the treatment of damage caused by cardiac arrest, therapeutic hypothermia is believed to improve patient outcome in a range of other conditions albeit with limited supporting evidence to date. BodyChillz Ltd is always looking to partner with research groups which are able to gain evidence for active cooling in areas such as traumatic brain injury, spinal cord injury, burns, cardiogenic shock following ST elevated myocardial infarction, febrile convulsion or perinatal asphyxial encephalopathy amongst others. If you are part of a regulated investigative group and would like more information, please use the contact us page to place an enquiry.