Potential long-term benefits of acute hypothermia after spinal cord injury: Assessments with somatosensory-evoked potentials*

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.

[1]  W. Wiederholt,et al.  Hypothermia-induced changes in rat short latency somatosensory evoked potentials. , 1981, Electroencephalography and clinical neurophysiology.

[2]  D. Burke,et al.  The Role of Directly Applied Hypothermia in Spinal Cord Injury , 2000, Spine.

[3]  Steven Vanni,et al.  Clinical Outcomes Using Modest Intravascular Hypothermia After Acute Cervical Spinal Cord Injury , 2010, Neurosurgery.

[4]  S. Haghighi,et al.  Effects of Altering Core Body Temperature on Somatosensory and Motor Evoked Potentials in Rats , 1992, Spine.

[5]  Michael S. Beattie,et al.  Graded Histological and Locomotor Outcomes after Spinal Cord Contusion Using the NYU Weight-Drop Device versus Transection , 1996, Experimental Neurology.

[6]  Nitish V Thakor,et al.  Quantitative assessment of somatosensory-evoked potentials after cardiac arrest in rats: Prognostication of functional outcomes* , 2010, Critical care medicine.

[7]  N. Thakor,et al.  Characterization of neurologic injury using novel morphological analysis of Somatosensory Evoked Potentials , 2010, 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology.

[8]  Michael G Fehlings,et al.  Emerging Repair, Regeneration, and Translational Research Advances for Spinal Cord Injury , 2010, Spine.

[9]  David W Howells,et al.  Hypothermia prior to decompression: buying time for treatment of acute spinal cord injury. , 2010, Journal of neurotrauma.

[10]  Yoshiki Nakamura,et al.  Induced hypothermia in experimental traumatic spinal cord injury: an update , 2003, Journal of the Neurological Sciences.

[11]  M. Farooque,et al.  Systemic hypothermia following spinal cord compression injury in the rat: axonal changes studied by β-APP, ubiquitin, and PGP 9.5 immunohistochemistry , 1999, Spinal Cord.

[12]  Leslie J. Bisson,et al.  The Use of Systemic Hypothermia for the Treatment of an Acute Cervical Spinal Cord Injury in a Professional Football Player , 2010, Spine.

[13]  D. Pearse,et al.  Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats , 2009, The Journal of comparative neurology.

[14]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[15]  Haruyasu Yamamoto,et al.  Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury , 2008, Spinal Cord.

[16]  T. Yaksh,et al.  Technique of selective spinal cord cooling in rat: methodology and application , 1997, Journal of Neuroscience Methods.

[17]  Jeff W. M. Bulte,et al.  Evoked potential and behavioral outcomes for experimental autoimmune encephalomyelitis in Lewis rats , 2010, Neurological Sciences.

[18]  W. D. Dietrich,et al.  Therapeutic hypothermia for spinal cord injury , 2009, Critical care medicine.

[19]  M. Farooque,et al.  Systemic hypothermia following spinal cord compression injury in the rat: an immunohistochemical study on MAP 2 with special reference to dendrite changes , 2000, Acta Neuropathologica.

[20]  R. Yezierski,et al.  Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. , 2000, Journal of neurotrauma.

[21]  O. Steward,et al.  Advances in the Management of Spinal Cord Injury , 1998, The Journal of the American Academy of Orthopaedic Surgeons.

[22]  J. Nolan,et al.  The role of hypothermia in post-cardiac arrest patients with return of spontaneous circulation: a systematic review. , 2011, Resuscitation.

[23]  R. Yezierski,et al.  Detrimental Effects of Systemic Hyperthermia on Locomotor Function and Histopathological Outcome after Traumatic Spinal Cord Injury in the Rat , 2001, Neurosurgery.

[24]  W. Dietrich,et al.  The effect of therapeutic hypothermia on the expression of inflammatory response genes following moderate traumatic brain injury in the rat. , 2005, Brain research. Molecular brain research.

[25]  D. Krieger,et al.  Cooling for Acute Ischemic Brain Damage (COOL AID): An Open Pilot Study of Induced Hypothermia in Acute Ischemic Stroke , 2001, Stroke.

[26]  C. Callaway.  Refining the use of therapeutic hypothermia after cardiac arrest. , 2011, Critical care medicine.

[27]  T. E. P. de Barros Filho,et al.  Analysis of The Sensitivity and Reproducibility Of The Basso, Beattie, Bresnahan (BBB) Scale in Wistar Rats , 2008, Clinics.

[28]  D. Marion,et al.  Current and future role of therapeutic hypothermia. , 2009, Journal of neurotrauma.

[29]  I. Jou.  Effects of Core Body Temperature on Changes in Spinal Somatosensory-Evoked Potential in Acute Spinal Cord Compression Injury: An Experimental Study in the Rat , 2000, Spine.

[30]  B. Green,et al.  Clinical application of modest hypothermia after spinal cord injury. , 2009, Journal of neurotrauma.

[31]  Karen Smith,et al.  Treatment of Comatose Survivors of Out-of-hospital Cardiac Arrest With Induced Hypothermia , 2003 .

[32]  Mao-tsun Lin,et al.  Body cooling ameliorating spinal cord injury may be neurogenesis-, anti-inflammation- and angiogenesis-associated in rats. , 2011, The Journal of trauma.

[33]  Y. Mahomed,et al.  Effects of hypothermia on short latency somatosensory evoked potentials in humans. , 1990, Electroencephalography and clinical neurophysiology.

[34]  A. Cappuccino,et al.  Systemic Hypothermia for the Treatment of Acute Cervical Spinal Cord Injury in Sports , 2011, Current sports medicine reports.

[35]  P. London.  Injury , 1969, Definitions.

[36]  B. Green,et al.  Hypothermia in spinal cord injury. , 1992, Journal of neurotrauma.

[37]  Philip F Stahel,et al.  Re: Cappuccino A, Bisson LJ, Carpenter B, et al. The use of systemic hypothermia for the treatment of an acute cervical spinal cord injury in a professional football player. Spine 2010;35:E57–62. , 2010, Spine.

[38]  H. Bramlett,et al.  Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia. , 2009, Journal of neurotrauma.

[39]  J. Fehrenbacher,et al.  Preservation of renal function utilizing hypothermic circulatory arrest in the treatment of distal thoracoabdominal aneurysms (types III and IV). , 2007, Annals of vascular surgery.