Beneficial effects of local profound hypothermia and the possible mechanism after experimental spinal cord injury in rats

Xu, Xiaoyu; Li, Ning; Zhu, Lin; Zhou, Yuan; Cheng, Huilin

doi:10.1179/2045772315y.0000000051

Cited by 9 publications

(6 citation statements)

References 45 publications

(46 reference statements)

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“…Of the 24 preclinical studies ( Table 1 ), most ( n = 21) employed a thoracic spinal cord model [ 5 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Twelve studies employed local cooling, eleven used systemic hypothermia, and one evaluated both application modalities.…”

Section: Resultsmentioning

confidence: 99%

Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review

Ransom

Brown

Pennington

et al. 2022

JCM

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Although hypothermia has shown to protect against ischemic and traumatic neuronal death, its potential role in neurologic recovery following traumatic spinal cord injury (TSCI) remains incompletely understood. Herein, we systematically review the safety and efficacy of hypothermia therapy for TSCI. The English medical literature was reviewed using PRISMA guidelines to identify preclinical and clinical studies examining the safety and efficacy of hypothermia following TSCI. Fifty-seven articles met full-text review criteria, of which twenty-eight were included. The main outcomes of interest were neurological recovery and postoperative complications. Among the 24 preclinical studies, both systemic and local hypothermia significantly improved neurologic recovery. In aggregate, the 4 clinical studies enrolled 60 patients for treatment, with 35 receiving systemic hypothermia and 25 local hypothermia. The most frequent complications were respiratory in nature. No patients suffered neurologic deterioration because of hypothermia treatment. Rates of American Spinal Injury Association (AIS) grade conversion after systemic hypothermia (35.5%) were higher when compared to multiple SCI database control studies (26.1%). However, no statistical conclusions could be drawn regarding the efficacy of hypothermia in humans. These limited clinical trials show promise and suggest therapeutic hypothermia to be safe in TSCI patients, though its effect on neurological recovery remains unclear. The preclinical literature supports the efficacy of hypothermia after TSCI. Further clinical trials are warranted to conclusively determine the effects of hypothermia on neurological recovery as well as the ideal means of administration necessary for achieving efficacy in TSCI.

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Section: Resultsmentioning

confidence: 99%

Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review

Ransom

Brown

Pennington

et al. 2022

JCM

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“…In another study, epidural perfusion was used in rats after SCI to induce local hypothermia (18°C) for 170 min with gradual rewarming to 37°C. Several beneficial effects were observed in rats subjected to hypothermia: downregulation of axon regeneration inhibitors (RhoA, ROCK-II, NG2, Neurocan, Brevican, and Nogo-A), decreased demyelination and enhanced axon regeneration, which ultimately resulted in recovery of hindlimb function (Xu et al, 2016). After the observation of promising results in rats, it was necessary to verify the effects of hypothermia in larger animal models (Kwon et al, 2015).…”

Section: Local Hypothermiamentioning

confidence: 99%

Hypothermia in the course of acute traumatic spinal cord injury

Kafka¹,

Lukáčová²,

Šulla³

et al. 2020

Acta Neurobiologiae Experimentalis

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In this review we briefly discuss animal experiments involving acute traumatic spinal cord injury (SCI) and the need for larger animals in testing experimental therapies. This literature overview, including the discussion of our own results from animal models, examines the use of hypothermia as a treatment method for SCI. Finally, we report the results of hypothermia application in clinical trials. Minipigs have been proposed as a potentially preferable model to rodents (typically rats) for predicting outcomes in human SCI due to their closer anatomical similarity to humans. In various animal studies, hypothermic treatment applied in the acute phase after SCI has resulted in neuroprotective effects, most likely due to inhibition of blood flow and oxygen consumption and reduction of overall metabolic activity and inflammation, resulting in improved nerve tissue sparing. Small-scale human clinical trials have been carried out, involving general (whole-body, systemic) or local hypothermia (close to the SCI site), with encouraging results. Nevertheless, further multi-center, randomized, double-blind studies with much larger patient numbers are necessary so that protocols can be standardized in order for hypothermia treatment to be reliably applied in clinical practice.

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“…In general, these studies showed that hypothermia is more effective when initiated early after injury and lasts for a longer time. Shorter duration may require more profound cooling to achieve similar effect ( 35 ). In general, these data suggest that long periods of local hypothermia are tolerated well and may improve long-term tissue sparing and functional outcome ( 14 , 35 , 40 – 43 , 47 , 57 , 87 ).…”

Section: Effects Of Hypothermia In Experimentsmentioning

confidence: 99%

“…Hypothermia also delays glutathione release, reduces oxidative stress and increases spinal cord tolerance to ischemia ( 23 – 26 ). There are also numerous articles illustrating the neuroprotective effect of hypothermia on neural stem cell differentiation and survival ( 15 , 27 – 35 ).…”

Section: Introductionmentioning

confidence: 99%

Hypothermic treatment after computer‑controlled compression in minipig: A preliminary report on the effect of epidural�vs.�direct spinal cord cooling

et al. 2018

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The aim of the present study was to investigate the therapeutic efficacy of local hypothermia (beginning 30 min post-injury persisting for 5 h) on tissue preservation along the rostro-caudal axis of the spinal cord (3 cm cranially and caudally from the lesion site), and the prevention of injury-induced functional loss in a newly developed computer-controlled compression model in minipig (force of impact 18N at L3 level), which mimics severe spinal cord injury (SCI). Minipigs underwent SCI with two post-injury modifications (durotomy vs. intact dura mater) followed by hypothermia through a perfusion chamber with cold (epidural t≈15°C) saline, DMEM/F12 or enriched DMEM/F12 (SCI/durotomy group) and with room temperature (t≈24°C) saline (SCI-only group). Minipigs treated with post-SCI durotomy demonstrated slower development of spontaneous neurological improvement at the early postinjury time points, although the outcome at 9 weeks of survival did not differ significantly between the two SCI groups. Hypothermia with saline (t≈15°C) applied after SCI-durotomy improved white matter integrity in the dorsal and lateral columns in almost all rostro-caudal segments, whereas treatment with medium/enriched medium affected white matter integrity only in the rostral segments. Furthermore, regeneration of neurofilaments in the spinal cord after SCI-durotomy and hypothermic treatments indicated an important role of local saline hypothermia in the functional outcome. Although saline hypothermia (24°C) in the SCI-only group exhibited a profound histological outcome (regarding the gray and white matter integrity and the number of motoneurons) and neurofilament protection in general, none of the tested treatments resulted in significant improvement of neurological status. The findings suggest that clinically-proven medical treatments for SCI combined with early 5 h-long saline hypothermia treatment without opening the dural sac could be more beneficial for tissue preservation and neurological outcome compared with hypothermia applied after durotomy.

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Beneficial effects of local profound hypothermia and the possible mechanism after experimental spinal cord injury in rats

Cited by 9 publications

References 45 publications

Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review

Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review

Hypothermia in the course of acute traumatic spinal cord injury

Hypothermic treatment after computer‑controlled compression in minipig: A preliminary report on the effect of epidural�vs.�direct spinal cord cooling

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