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

Abstract

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.

Porcine Model of Spinal Cord Injury: A Systematic Review

“… 17 Gedrova and colleagues created a 20-point scale where 1–8 represent slight or extensive movement for each individual joint of the hindlimbs, 9–11 represent sweeping and the ability to get up by itself (though without the ability to maintain balance), and 12–20 characterize the ability to walk a few steps without forelimb/hindlimb coordination to consistent stepping. 49 , 50 Santamaria and colleagues developed the Miami Porcine Walking Scale, a 10-point scale based on hindlimb stepping and weight bearing with 1 corresponding to complete paraplegia and 10 indicating no apparent deficit. 9 , 26 The Tarlov scale, used by Zurita and colleagues, is a similar 10-point scale of hindlimb motor function.…”

“…Hypothermia has been explored as another anti-inflammatory tool by reducing metabolic consumption, energy demands, local edema, and oxidative stress. 49 , 50 Once again, studies on the porcine model have shown mixed efficacy. Gedrova and colleagues found that local hypothermia improved hindlimb recovery in mild SCI, but not in severe injuries.…”

“… 49 Zavodska and colleagues found that hypothermia with or without a durotomy led to no significant improvements in neurological status, although hypothermia after durotomy improved white matter integrity and led to regeneration of neurofilaments. 50 Additional studies are needed to further evaluate any potential therapeutic efficacy of hypothermia.…”

Autonomic Dysreflexia following Spinal Cord Injury

“…Various therapeutic measures, such as hypothermia, neuroprotective drugs, genetic manipulation of intraspinal plasticity, or reparative strategies, have been proposed to ameliorate, suppress, or reverse the activity of numerous negative factors contributing to the expansion of necrosis, and accentuating the tissue damage within the secondary phase of SCI. 61 62 63 64 65 66 …”

Hypothermia in the course of acute traumatic spinal cord injury

“…In our previous experiment, we studied the effects of local hypothermia on selected parameters in a minipig model of contusion SCI using a computerized compression device. In this model we were able to scale the impact strength (8N, 15N, 18N) and thus compare the findings for varied degrees of contusion (Gedrova et al, 2018;Zavodska et al, 2018). In the control (normothermic) group, the graded lesion at the impact site was recorded as 47% loss of tissue with a force of 8N impact, 67% loss of tissue with a force of 15N impact and 79% loss of tissue with a force of 18N impact after 9 weeks of survival.…”