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Comparative Study
, 40 (2), 573-9

Potential Long-Term Benefits of Acute Hypothermia After Spinal Cord Injury: Assessments With Somatosensory-Evoked Potentials

Affiliations
Comparative Study

Potential Long-Term Benefits of Acute Hypothermia After Spinal Cord Injury: Assessments With Somatosensory-Evoked Potentials

Anil Maybhate et al. Crit Care Med.

Abstract

Objective: Neuroprotection by hypothermia has been an important research topic over last two decades. In animal models of spinal cord injury, the primary focus has been assessing the effects of hypothermia on behavioral and histologic outcomes. Although a few studies have investigated electrophysiological changes in descending motor pathways with motor-evoked potentials recorded during cooling, we report here hypothermia induced increased electrical conduction in the ascending spinal cord pathways with somatosensory-evoked potentials in injured rats. In our experiments, these effects lasted long after the acute hypothermia and were accompanied by potential long-term improvements in motor movement.

Design: Laboratory investigation.

Setting: University medical school.

Subjects: Twenty-one female Lewis rats.

Interventions: Hypothermia.

Measurements and main results: All animals underwent spinal cord contusion with the NYU-Impactor by a 12.5-mm weight drop at thoracic vertebra T8. A group (n = 10) was randomly assigned for a systemic 2-hr hypothermia episode (32 ± 0.5°C) initiated approximately 2.0 hrs postinjury. Eleven rats were controls with postinjury temperature maintained at 37 ± 0.5°C for 2 hrs. The two groups underwent preinjury, weekly postinjury (up to 4 wks) somatosensory-evoked potential recordings and standard motor behavioral tests (BBB). Three randomly selected rats from each group were euthanized for histologic analysis at postinjury day 3 and day 28. Compared with controls, the hypothermia group showed significantly higher postinjury somatosensory-evoked potential amplitudes with longer latencies. The BBB scores were also higher immediately after injury and 4 wks later in the hypothermia group. Importantly, specific changes in the Basso, Beattie, Bresnahan scores in the hypothermia group (not seen in controls) indicated regained functions critical for motor control. Histologic evaluations showed more tissue preservation in the hypothermia group.

Conclusions: After spinal cord injury, early systemic hypothermia provided significant neuroprotection weeks after injury through improved sensory electrophysiological signals in rats. This was accompanied by higher motor behavioral scores and more spared tissue in acute and postacute periods after injury.

Conflict of interest statement

The authors have not disclosed any potential conflicts of interest.

Figures

Figure 1
Figure 1
Recorded rectal temperature (Mean ± SEM) in a group of n = 10 rats after induction of spinal cord contusion. The temperature control was initiated (t = 0 in the plot) within ~30 mins of a contusive spinal cord injury (T8) with 12.5 mm weight drop using the NYU impactor. For the first ~ 2 hrs, (shaded red) the temperature was held constant (37 ± 0.5°C). Systemic hypothermia was induced with cooling down to 32 ± 0.5 °C (A–B) after which the temperature was again held constant at 32 ± 0.5°C for ~2 hrs (B–C). This was followed by gradual warming (C–D) back to 37 ± 0.5 °C and then removal of the heating pad beyond line D. A normothermia group (n = 11) with constant temperature 37 ± 0.5 °C was used as controls.
Figure 2
Figure 2
Panels show changes over 4 weeks, in somatosensory evoked potentials (SSEP) upon hindlimb stimulation in two representative rats after a thoracic spinal cord contusion (T8) with a NYU impactor (12.5 mm impact height). Left: A rat with normothermia; Right: A rat subjected to an acute 2 hr systemic hypothermia (32 ± 0.5°C) initiated 2hrs after the contusion.
Figure 3
Figure 3
SSEP amplitudes (top panels) and N1 peak latencies (bottom panels) upon stimulation of the two hindlimbs for two groups of rats after SCI at T8 with impact height 12.5 mm. Blue: acute, 2 hr hypothermia (n = 7; 32 ± 0.5 °C); Gray: Normothermia (n = 8; 37 ± 0.5 °C). B = Baseline; D4–D28 denote Days 4, 7, 14, 21, 28 after injury. It is important to note that no deleterious effects from hypothermia were detected in any rat as would have been indicated by decreases in SSEP amplitude (*p<0.01 between treatment groups; Mean ± SEM).
Figure 4
Figure 4
Variation in BBB scores (Mean ± SEM) over a period of 28 days in the two groups, normothermia (n = 8; red) and hypothermia (n=7; blue). It should be noted that a change in the BBB score from 11 to 14 is a critical milestone in recovery. It is the difference between an animal having almost no front-hind limb coordination with only occasional weight supported plantar steps and a consistent coordinated front-hind limb motion with consistent plantar steps. The hypothermia group exceeded this benchmark in recovery while the normothermia group did not. (*p<0.002;**p<0.00004).
Figure 5
Figure 5
Four representative spinal cord histological sections at the site of injury of each treatment group at 3 days (A–B) and at 1 month (C–D), stained with H&E. At 3 days, better preservation of morphology was observed in the hypothermia-treated rat (A) than in the untreated rat (B). Tissue analysis showed that preservation of gray matter at 3 days post-injury (e) was significantly better in the hypothermia-treated rat than in the untreated rat. At 1 month, there were no significant difference in observable morphology between the hypothermia-treated rat (C) and the untreated rat (D), which is reflected in the analysis of gray and white matter tissue sparing.

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