Neuroprotection by Therapeutic Hypothermia

Abstract

Hypothermia therapy is an old and important method of neuroprotection. Until now, many neurological diseases such as stroke, traumatic brain injury, intracranial pressure elevation, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy have proven to be suppressed by therapeutic hypothermia. Beneficial effects of therapeutic hypothermia have also been discovered, and progress has been made toward improving the benefits of therapeutic hypothermia further through combination with other neuroprotective treatments and by probing the mechanism of hypothermia neuroprotection. In this review, we compare different hypothermia induction methods and provide a summarized account of the synergistic effect of hypothermia therapy with other neuroprotective treatments, along with an overview of hypothermia neuroprotection mechanisms and cold/hypothermia-induced proteins.

Insightful Backbone Modifications Preventing Proteolytic Degradation of Neurotensin Analogs Improve NTS1-Induced Protective Hypothermia

“…Hypothermia therapy has been found to exert neuroprotective effects in many neurological diseases, such as stroke, traumatic brain injury, intracranial pressure elevation, and neonatal encephalopathy (Huber et al, 2019;Sun et al, 2019). In light of this, there is now growing evidence demonstrating that NT(8-13) analogs induce regulated reduction of body and brain temperatures through activation of the NTS1 receptor subtype (Liu et al, 2016).…”

“…Mild hypothermia (32-35 • C) has been proven to exert neuroprotective effects in a variety of neurological conditions, such as global ischemia after cardiac arrest, hypoxic-ischemic encephalopathy, ischemic stroke, and traumatic injury (Huber et al, 2019). Indeed, therapeutic cooling has been described to counteract many of the deleterious processes occurring in the setting of cerebral ischemia, including neuroinflammation, free radical production, excitotoxicity, and apoptosis, as well as blood-brain barrier disruption (Sun et al, 2019). To date, hypothermia is achieved by internal or external cooling interventions (Chen et al, 2014).…”

“…To date, hypothermia is achieved by internal or external cooling interventions (Chen et al, 2014). However, these physical methods have serious limitations, which include slow onset of action, undesirable shivering and vasoconstriction responses, need for general anesthesia, and poor ability to implement in an out-of-hospital environment (Sun et al, 2019). There is, therefore, a growing interest to develop drugs that safely reduce the body temperature by controlling the hypothalamic set point (Kurisu et al, 2019).…”

Blood-brain barrier transport using a high-affinity, brain-selective VNAR (Variable Domain of New Antigen Receptor) antibody targeting transferrin receptor 1

“…Interestingly, the potency of TXB2-hFc-NT was 50-fold greater than Angiopep-2-NT in lowering body temperature, which may reflect the ability of the TXB2-hFc shuttle to deliver the cargo across the BBB and directly target TfR1-expressing neurons. The use of mild to moderate pharmacologically induced hypothermia has shown potential in traumatic brain injury and stroke in various experimental models and in clinical trials [50,51]. Therefore, the use of targeted delivery of neurotensin to the brain by TXB2 via IV administration might provide a significant improvement to induction of hypothermia.…”

Prolonged astrocyte-derived erythropoietin expression attenuates neuronal damage under hypothermic conditions

“…Approximately 50% of newborns with moderate to severe HIE still die or suffer from long-term disabilities [1]. Many mechanisms have been proposed to explain the effects of TH, including the suppression of apoptosis, decreased inflammation, reduced levels of excitatory amino acids, reduced levels of reactive oxygen species, and a reduced cerebral metabolic rate [5,6]. However, the cellular mechanism underlying the neuroprotective effect of TH is complex and has not yet been fully elucidated.…”