Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions

Abstract

Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. The myriad of protective mechanisms of hypothermia include the slowing down of metabolism, decreasing free radical generation, inhibiting excitotoxicity and apoptosis, ameliorating inflammation, preserving the blood spinal cord barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing axonal damage and encouraging neurogenesis. Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia’s therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair.

Traumatic spinal cord injury: current concepts and treatment update

“…In animal studies, hypothermia decreased basal metabolic rate in the central nervous system, reduced inflammation, apoptosis, excitotoxicity, edema, gliosis, and increased angiogenesis. As well, traumatic SCI models showed improvement with the decreased temperature 30 . A small pilot study in humans with SCI exposed to hypothermia showed a trend towards neurological recovery (43% vs 21%) and no difference in complication rates 31 .…”

Mesenchymal stromal cells as a choice for spinal cord injury treatment

“…Many of these neuroprotective agents have been studied, but without positive results for thoracic spinal cord injury patients [23,24] . Riluzole, a sodium channel blocker, and hypothermia, which decreases central nervous system metabolism, have been shown to be effective neuroprotective agents for the treatment of spinal cord injury [16,[25][26][27] . Mu et al [28] associated riluzole and MPSS in rats with spinal cord injury.…”

A review of novel trends in management of canine spinal cord injury

“…Experimental studies as well as clinical experience show that hypothermia can improve the neurological outcome in patients following traumatic and ischaemic brain or SC lesions (Martyrosian et al 2017). The reduction of body temperature divides hypothermia into profound (< 30 °C), moderate (30-32 °C), modest (32-34 °C) and mild (35 °C) (Wang and Pearse 2015). Hypothermia inhibits cellular metabolism by 5-8% per 1 °C, retards basic enzymatic activity, reduces oxygen consumption, and energy demand (Wang and Pearse 2015).…”

“…The reduction of body temperature divides hypothermia into profound (< 30 °C), moderate (30-32 °C), modest (32-34 °C) and mild (35 °C) (Wang and Pearse 2015). Hypothermia inhibits cellular metabolism by 5-8% per 1 °C, retards basic enzymatic activity, reduces oxygen consumption, and energy demand (Wang and Pearse 2015). Hypothermia increases adenosine triphosphate (ATP) stores, helps to maintain the normal transmembrane ion and neurotransmitter gradients, preserve the BSCB (blood-spinal cord barrier), ameliorate the local oedema, suppress axonal swelling and development of gliosis, reduce oxidative stress, inflammation, and mitochondrial membrane permeabilization which is the point-of-no-return in apoptosis (Alkabie and Boileau 2016).…”