Beneficial effects of modest systemic hypothermia on locomotor function and histopathological damage following contusion-induced spinal cord injury in rats

Abstract

<jats:p content-type="fine-print"><jats:italic>Object.</jats:italic> Local spinal cord cooling (LSCC) is associated with beneficial effects when applied following ischemic or traumatic spinal cord injury (SCI). However, the clinical application of LSCC is associated with many technical difficulties such as the requirement of special cooling devices, emergency surgery, and complicated postoperative management. If hypothermia is to be considered for future application in the treatment of SCI, alternative approaches must be developed. The objectives of the present study were to evaluate 1) the relationship between systemic and epidural temperature after SCI; 2) the effects of modest systemic hypothermia on histopathological damage at 7 and 44 days post-SCI; and 3) the effects of modest systemic hypothermia on locomotor outcome at 44 days post-SCI.</jats:p> <jats:p content-type="fine-print"><jats:italic>Methods.</jats:italic> A spinal cord contusion (12.5 mm at T-10) was produced in adult rats that had been randomly divided into two groups. Group 1 rats (seven in Experiment 1; 12 in Experiment 2) received hypothermic treatment (epidural temperature 32–33°C) 30 minutes postinjury for 4 hours; Group 2 rats (nine in Experiment 1; eight in Experiment 2) received normothermic treatment (epidural temperature 37°C) 30 minutes postinjury for 4 hours. Blood pressure, blood gas levels, and temperatures (epidural and rectal) were monitored throughout the 4-hour treatment period. Twice weekly assessment of locomotor function was performed over a 6-week survival period by using the Basso-Beattie-Bresnahan locomotor rating scale. Seven (Experiment 1) and 44 (Experiment 2) days after injury, animals were killed, perfused, and their spinal cords were serially sectioned. The area of tissue damage was quantitatively analyzed from 16 longitudinal sections selected from the central core of the spinal cord.</jats:p> <jats:p content-type="fine-print"><jats:italic>Conclusions.</jats:italic> The results showed that 1) modest changes in the epidural temperature of the spinal cord can be produced using systemic hypothermia; 2) modest systemic hypothermia (32–33°C) significantly protects against locomotor deficits following traumatic SCI; and 3) modest systemic hypothermia (32–33°C) reduces the area of tissue damage at both 7 and 44 days postinjury. Although additional research is needed to study the therapeutic window and long-term benefits of systemic hypothermia, these data support the possible use of modest systemic hypothermia in the treatment of acute SCI.</jats:p>

Hypothermic Treatment for Acute Spinal Cord Injury

“…Martinez-Arizala and Green showed that both pre-and post-treatment with hypothermia (31-32°C) appeared to be effective in reducing the degree of hemorrhage at the site of SCI [24]. In other studies, more moderate degrees of systemic hypothermia have also been shown to promote motor recovery in both thoracic and cervical SCI models [7,25]. In one study by Yu et al [25], a whole-body moderate hypothermia (33°C) initiated by blowing cool air onto the surface of the rat led to significantly improved locomotive function, as assessed by the Basso, Beattie and Bresnahan (BBB) [69] open-field scoring system.…”

“…However, more recently, the beneficial effects of more modest levels of hypothermia has been appreciated [7,[20][21][22][23][24][25]. In the 1980s, studies showed for the first time that relatively small reductions in brain tissue temperature provided significant protection against ischemic and traumatic neuronal cell death [7].…”

“…In terms of SCI, published data have shown that relatively mild levels of hypothermia introduced after a traumatic or compressive SCI provides some degree of improvement in function and reduces the histopathological damage [22,[25][26][27][28][29][30][31][32][33][34][35][36][37]. In clinically relevant SCI studies, mild reductions in temperature have been shown to be protective, whereas mild elevations (hyperthermia) have been reported to worsen outcome [38][39][40].…”

Recomendaciones –guía– en la lesión aguda medular intraoperatoria en cirugía correctora del raquis

“…En la reparación de aneurismas aórticos el drenaje externo controlado (10 mm Hg o 13 cm H 2 O) de LCR disminuye la incidencia de déficit neurológico postoperatorio, por lo que sería una terapia razonable en situación inminente de isquemia medular durante la cirugía correctora del raquis 13,[56][57][58][59] . A nivel experimental, la hipotermia sistémica inducida tiene propiedades neuroprotectoras frente a la isquemia cerebral 60 y medular 61,62 , aunque en el neurotrauma y la neurocirugía vascular no ha conseguido mejorar el resultado neurológico 63,64 . En la profilaxis de la isquemia medular durante la cirugía aórtica la hipotermia regional medular mediante enfriamiento epidural demuestra citoprotección 65 , aunque por lo engorroso del procedimiento se opta por la hipotermia sistémica 13 .…”

Confirming an experimental therapy prior to transfer to humans: What is the ideal?

“…To date, several treatments have been reported to promote a degree of axonal regeneration and functional recovery in the spinal cord [3][4][5][6][7][8][9][10][11][12][13][14]. Also, several neuroprotective strategies administered in the acute injury setting have shown promise in reducing secondary injury mechanisms and promoting recovery [15][16][17][18][19][20][21][22]. Thus, an important question now being discussed in the scientific community is whether these neuroprotective or regenerative strategies are ready for clinical application [23].…”