Potential long-term benefits of acute hypothermia after spinal cord injury

Abstract

Objective Neuroprotection by hypothermia has been an important research topic over last two decades. In animal models of spinal cord injury (SCI), the primary focus has been assessing effects of hypothermia on behavioral and histological outcomes. While 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 (SSEPs) in injured rats. In our experiments these effects lasted long after the acute hypothermia and were accompanied with potential long term improvements in motor movement. Design Laboratory Investigation. Setting University Medical School. Subjects 21 Female Lewis Rats. Interventions Hypothermia. Measurements and Main Results All animals underwent spinal cord contusion, with the NYU-Impactor, by a 12.5mm weight drop at thoracic vertebra T8. A group (n=10) was randomly assigned for a systemic 2hr. hypothermia episode (32±0.5°C) initiated ~2.0hrs post-injury. 11 rats were controls with post-injury temperature maintained at 37±0.5°C for 2hrs. The two groups underwent pre-injury, weekly post-injury (up to 4wks) SSEP recordings and standard motor behavioral tests (BBB). Three randomly selected rats from each group were euthanized for histological analysis at post-injury Day 3 and Day 28. Compared to controls, the hypothermia group showed significantly higher SSEP amplitudes post-injury; with longer latencies. The BBB scores were also higher immediately after injury and 4 weeks later in the hypothermia group. Importantly, specific changes in the BBB scores in hypothermia group (not seen in controls) indicated regained functions critical for motor control. Histological evaluations showed more tissue preservation in hypothermia group. Conclusions Post-SCI, early systemic hypothermia provided significant neuroprotection weeks after injury via improved sensory electrophysiological signals in rats. This was accompanied by higher motor behavioral scores and more spared tissue in acute and post-acute periods after injury.

The Effects of Local and General Hypothermia on Temperature Profiles of the Central Nervous System Following Spinal Cord Injury in Rats

“…The core temperature was maintained at 37°C -0.5°C with the help of a heating pad for 1 hour after the time of contusion or laminectomy and prior to inducing hypothermia. After 1 hour, general hypothermia was induced by spraying the rat with alcohol mist (70% ethanol) and using an electric fan until the core temperature dropped to 32°C -0.5°C, as previously described (Shin et al, 2006;Jia et al, 2008;Maybhate et al, 2012). The induction period lasted 25 to 30 minutes.…”

“…We previously showed that 2-hour general hypothermia in rats with moderate contusive SCI leads not only to improved motor behavior and increased somatosensory evoked potential (SSEP) amplitude, but also to increased N1-latency of SSEP, for up to 4 weeks after injury (Maybhate et al, 2012). Because SSEPs are the response at the primary somatosensory cortex to stimulus of the periphery, a key question is how cortical temperature is affected during the period of hypothermia administration.…”

“…H ypothermia for treatment of patients with spinal cord injury (SCI) shows great promise as an acute neuroprotective therapy (Dietrich et al, 2009(Dietrich et al, , 2011Dietrich, 2012;Maybhate et al, 2012;Silasi et al, 2012). In addition to SCI, hypothermia has been shown to lead to functional improvements in many other injury types, including cardiac arrest (Arrich, 2007;Madhok et al, 2010;Beddingfield and Clark, 2012), stroke (Groysman et al, 2011;Chang and Marshall, 2012;Lakhan and Pamplona, 2012), ischemiareperfusion injury (Kawamura et al, 2006), traumatic brain injury (Tomura et al, 2012), and coma (Bouwes et al, 2012).…”

Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study

“…4,5 A recent study revealed beneficial effect of hypothermia on somato-sensory and motor-evoked potentials. 6 Our reported experience of 14 cervical SCI patients revealed that systemic hypothermia induced via an intravascular catheter and continued for 48 h showed improved functional outcome and appeared safe compared with a historical control group. 7,8 In this article we describe a larger series of cervical SCI patients based on our extended, single center experience of hypothermia treatment that now spans over 6 years.…”

“…4,5 A recent study revealed beneficial effect of hypothermia on somato-sensory and motor-evoked potentials. 6 Our reported experience of 14 cervical SCI patients revealed that systemic hypothermia induced via an intravascular catheter and continued for 48 h showed improved functional outcome and appeared safe compared with a historical …”