Experimental Hypothermia Murine Model for Spinal Cord Injury Studies
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Published:
Feb 14, 2022
Keywords:
Hypothermia, murines, spinal cord
Main Article Content
Abstract
Introduction: Given the complexity of hypothermal trial systems in murines, they are expensive. Our objective was to evaluate if the exogenous hypothermal model used in our laboratory for ocular hypothermia was useful for a significant reduction in medullar spine temperature in adult murines.
Materials and Methods: 36 60-day-old adult male Sprague-Dawley rats were used. They were separated into two groups: a normal temperature group at 24 °C (n=18) and a hypothermia group in a cold chamber at 8 °C for 180 minutes (n=18).
Results: The mean rectal temperature was 37.71 ºC ± 0.572 in the normothermia group and 34.03ºC ± 0.250 in the hypothermia group (p <0.0001). The mean medullar temperature was 38.8 ± 0.468 ºC in the normothermia group and 36.4 ± 0.290 ºC in the hypothermia group (p <0.0001).
Conclusion: Using systematic hypothermia in lab rats seems to be promising to evaluate physiologic and pathological mechanisms triggered in the medullar spine. Exposure to cold in the external chamber producessignificant medullar hypothermia in adult rats. Results suggest this might be an adequate and inexpensive medullar hypothermal model.
Materials and Methods: 36 60-day-old adult male Sprague-Dawley rats were used. They were separated into two groups: a normal temperature group at 24 °C (n=18) and a hypothermia group in a cold chamber at 8 °C for 180 minutes (n=18).
Results: The mean rectal temperature was 37.71 ºC ± 0.572 in the normothermia group and 34.03ºC ± 0.250 in the hypothermia group (p <0.0001). The mean medullar temperature was 38.8 ± 0.468 ºC in the normothermia group and 36.4 ± 0.290 ºC in the hypothermia group (p <0.0001).
Conclusion: Using systematic hypothermia in lab rats seems to be promising to evaluate physiologic and pathological mechanisms triggered in the medullar spine. Exposure to cold in the external chamber producessignificant medullar hypothermia in adult rats. Results suggest this might be an adequate and inexpensive medullar hypothermal model.
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How to Cite
Sarotto, A. J., Contartese, D., Dorfman, V., Toscanini, A., Scheverin, N., Besse, M., Larráyoz, I., Rey-Funes, M., Martínez, A., & Loidl, C. F. (2022). Experimental Hypothermia Murine Model for Spinal Cord Injury Studies. Revista De La Asociación Argentina De Ortopedia Y Traumatología, 87(1), 89-94. https://doi.org/10.15417/issn.1852-7434.2022.87.1.1420
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Basic Research
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https://doi.org/10.1002/jnr.22556
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9. Horiuchi T, Kawaguchi M, Kurita N, Inoue S, Nakamura M, et al. The long-term effects of mild to moderate
hypothermia on gray and white matter injury after spinal cord ischemia in rats. Anesth Analg 2009;109(2):559-66.
https://doi.org/10.1213/ane.0b013e3181aa96a1
10. Beckman JS, Koppenol WH, Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996;271(5 Pt 1):C1424-37. https://doi.org/10.1152/ajpcell.1996.271.5.C1424
11. Bazley FA, Pashai N, Kerr CL, All AH. The effects of local and general hypothermia on temperature profiles of
the central nervous system following spinal cord injury in rats. Ther Hypothermia Temp Manag 2014;4(3): 115-24.
https://doi.org/10.1089/ther.2014.0002
12. Badr El-Bialy, Shaimaa Abu Zaid, Nermeen El-Borai, Anis Zaid, Amanallah El-Bahrawy. Hypothermia in rat:
Biochemical and pathological study. Int J Cri For Sci 2017;1(1):22-30. [Consulta: marzo 2019] Disponible en:
https://biocoreopen.org/ijcf/Hypothermia-in-Rat-Biochemical-and-Pathological-Study.php
13. Liu P, Yang R, Zuo Z. Application of a novel rectal cooling device in hypothermia therapy after cerebral hypoxiaischemia in rats. BMC Anesthesiol 2016;16:77. https://doi.org/10.1186/s12871-016-0239-5
14. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate Hypothermia to treat
perinatal asphyxia encephalopathy. N Engl J Med 2009;361(14):1349-58. https://doi.org/10.1056/NEJMoa0900854
15. Battin MR, Penrice J, Gunn TR, Gunn AJ. Treatment of term infants with head cooling and mild systemic
hypothermia (35 degrees C and 34,5 degrees C) after perinatal asphyxia. Pediatrics 2003;111(2):244-51.
https://doi.org/10.1542/peds.111.2.244
16. Dietrich WD, Levi AD, Wang M, Green BA. Hypothermic treatment for acute spinal cord injury. Neurotherapeutics 2011;8(2):229-39. https://doi.org/10.1007/s13311-011-0035-3
17. Tay Bobby K-B, Eismont FJ. Injuries of the upper cervical spine. En: Herkowitz HN. Rothman-Simeone The Spine, 5th ed. Philadelphia: Saunders; 1980, vol. II, cap. 67, págs. 1073-99.
18. Videla N, Steverlynck A, Castelli R, Sarotto AJ, Sbrero D, Scheveri N, et al. Incidencia de lesiones espinales
en accidentes de tránsito. Nuestra experiencia, análisis y conclusiones sobre la prevalencia de lesiones por
motocicletas. XVIII Congreso Argentino de la Sociedad Argentina de Patología de la Columna Vertebral, Córdoba,
Argentina, 2014.
19. Cambria RP, Davison JK. Regional hypothermia for prevention of spinal cord ischemic complications after
thoracoabdominal aortic surgery: experience with epidural cooling. Semin Thorac Cardiovasc Surg 1998;10(1):61-
5. https://doi.org/10.1016/s1043-0679(98)70020-6
20. Choi R, Andres RH, Steinberg GK, Guzman R. Intraoperative hypothermia during vascular neurosurgical
procedures. Neurosurg Focus 2009;26(5):E24. https://doi.org/10.3171/2009.3.FOCUS0927
21. Lo TP, Cho K-S, Garg MS, Lynch MP, Marcillo AE, Koivisto DL, et al. Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol 2009;514(5):433-48. https://doi.org/10.1002/cne.22014
22. Shibuya S, Miyamoto O, Janjua NA, Itano T, Mori S, Horimatsu H. Post-traumatic moderate systemic hypothermia reduces TUNEL positive cells following spinal cord injury in rat. Spinal Cord 2004;42(1):29-34.
https://doi.org/10.1038/sj.sc.3101516
23. Morrison SF. Central neural control of thermoregulation and brown adipose tissue. Auton Neurosci 2016;196:14-24. https://doi.org/10.1016/j.autneu.2016.02.010
24. Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JKJ, et al. Hypothermia for Intracranial
Hypertension after Traumatic Brain Injury. N Engl J Med 2015;373(25):2403-12. https://doi.org/10.1056/NEJMoa1507581
25. Dingley J, Liu X, Gill H, Smit E, Sabir H, Tooley J, et al. The feasibility of using a portable xenon delivery device
to permit earlier xenon ventilation with therapeutic cooling of neonates during ambulance retrieval. Anesth Analg 2015;120(6):1331-6. https://doi.org/10.1213/ANE.0000000000000693
cord as a result of perinatal asphyxia is involved in behavioral disabilities: hypothermia as preventive treatment. J
Neurosci Res 2009;87(5):1260-9. https://doi.org/10.1002/jnr.21922
2. Loidl CF, De Vente J, van Dijk E, Vles SH, Steinbusch H, Blanco C. Hypothermia during or after severe perinatal
asphyxia prevents increase in cyclic GMP-related nitric oxide levels in the newborn rat striatum. Brain Res
1998;791(1-2):303-7. https://doi.org/10.1016/s0006-8993(98)00195-4
3. Rey-Funes M, Ibarra ME, Dorfman VB, Loidl CF, Serrano J, Fernándes AP, et al. Hypothermia prevents nitric oxide system changes in retina induced by severe perinatal asphyxia. J Neurosci Res 2011;89(5):729-43.
https://doi.org/10.1002/jnr.22556
4. Rey-Funes M, Dorfman VB, Ibarra ME, Peña E, Contartese DS, et al. Hypothermia prevents gliosis and
angiogenesis development in an experimental model of ischemic proliferative retinopathy. Invest Ophthalmol Vis Sci 2013;54(4):2836-46. https://doi.org/10.1167/iovs.12-11198
5. Larrayoz IM, Rey-Funes M, Contartese DS, Rolón F, Sarotto A, et al. Cold shock proteins are expressed in the
retina following exposure to low temperatures. PLoS One 2016;11(8):e0161458. https://doi.org/10.1371/journal.pone.0161458
6. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory
Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press
(US); 2011. PMID: 21595115
7. Reglamento para el cuidado y uso de animales de laboratorio en la Universidad de Buenos Aires. CICUAL.
[Consulta: marzo 2019] Disponible en: https://www.fmed.uba.ar/sites/default/files/2018-04/Reglamento%20UBA_0.pdf
8. Busto R, Dietrich WD, Globus MY, Valdes I, Scheinberg P, Ginsberg MD. Small differences in intraischemic brain
temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 1987;7(6):29-38. https://doi.org/10.1038/jcbfm.1987.127
9. Horiuchi T, Kawaguchi M, Kurita N, Inoue S, Nakamura M, et al. The long-term effects of mild to moderate
hypothermia on gray and white matter injury after spinal cord ischemia in rats. Anesth Analg 2009;109(2):559-66.
https://doi.org/10.1213/ane.0b013e3181aa96a1
10. Beckman JS, Koppenol WH, Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996;271(5 Pt 1):C1424-37. https://doi.org/10.1152/ajpcell.1996.271.5.C1424
11. Bazley FA, Pashai N, Kerr CL, All AH. The effects of local and general hypothermia on temperature profiles of
the central nervous system following spinal cord injury in rats. Ther Hypothermia Temp Manag 2014;4(3): 115-24.
https://doi.org/10.1089/ther.2014.0002
12. Badr El-Bialy, Shaimaa Abu Zaid, Nermeen El-Borai, Anis Zaid, Amanallah El-Bahrawy. Hypothermia in rat:
Biochemical and pathological study. Int J Cri For Sci 2017;1(1):22-30. [Consulta: marzo 2019] Disponible en:
https://biocoreopen.org/ijcf/Hypothermia-in-Rat-Biochemical-and-Pathological-Study.php
13. Liu P, Yang R, Zuo Z. Application of a novel rectal cooling device in hypothermia therapy after cerebral hypoxiaischemia in rats. BMC Anesthesiol 2016;16:77. https://doi.org/10.1186/s12871-016-0239-5
14. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate Hypothermia to treat
perinatal asphyxia encephalopathy. N Engl J Med 2009;361(14):1349-58. https://doi.org/10.1056/NEJMoa0900854
15. Battin MR, Penrice J, Gunn TR, Gunn AJ. Treatment of term infants with head cooling and mild systemic
hypothermia (35 degrees C and 34,5 degrees C) after perinatal asphyxia. Pediatrics 2003;111(2):244-51.
https://doi.org/10.1542/peds.111.2.244
16. Dietrich WD, Levi AD, Wang M, Green BA. Hypothermic treatment for acute spinal cord injury. Neurotherapeutics 2011;8(2):229-39. https://doi.org/10.1007/s13311-011-0035-3
17. Tay Bobby K-B, Eismont FJ. Injuries of the upper cervical spine. En: Herkowitz HN. Rothman-Simeone The Spine, 5th ed. Philadelphia: Saunders; 1980, vol. II, cap. 67, págs. 1073-99.
18. Videla N, Steverlynck A, Castelli R, Sarotto AJ, Sbrero D, Scheveri N, et al. Incidencia de lesiones espinales
en accidentes de tránsito. Nuestra experiencia, análisis y conclusiones sobre la prevalencia de lesiones por
motocicletas. XVIII Congreso Argentino de la Sociedad Argentina de Patología de la Columna Vertebral, Córdoba,
Argentina, 2014.
19. Cambria RP, Davison JK. Regional hypothermia for prevention of spinal cord ischemic complications after
thoracoabdominal aortic surgery: experience with epidural cooling. Semin Thorac Cardiovasc Surg 1998;10(1):61-
5. https://doi.org/10.1016/s1043-0679(98)70020-6
20. Choi R, Andres RH, Steinberg GK, Guzman R. Intraoperative hypothermia during vascular neurosurgical
procedures. Neurosurg Focus 2009;26(5):E24. https://doi.org/10.3171/2009.3.FOCUS0927
21. Lo TP, Cho K-S, Garg MS, Lynch MP, Marcillo AE, Koivisto DL, et al. Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol 2009;514(5):433-48. https://doi.org/10.1002/cne.22014
22. Shibuya S, Miyamoto O, Janjua NA, Itano T, Mori S, Horimatsu H. Post-traumatic moderate systemic hypothermia reduces TUNEL positive cells following spinal cord injury in rat. Spinal Cord 2004;42(1):29-34.
https://doi.org/10.1038/sj.sc.3101516
23. Morrison SF. Central neural control of thermoregulation and brown adipose tissue. Auton Neurosci 2016;196:14-24. https://doi.org/10.1016/j.autneu.2016.02.010
24. Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JKJ, et al. Hypothermia for Intracranial
Hypertension after Traumatic Brain Injury. N Engl J Med 2015;373(25):2403-12. https://doi.org/10.1056/NEJMoa1507581
25. Dingley J, Liu X, Gill H, Smit E, Sabir H, Tooley J, et al. The feasibility of using a portable xenon delivery device
to permit earlier xenon ventilation with therapeutic cooling of neonates during ambulance retrieval. Anesth Analg 2015;120(6):1331-6. https://doi.org/10.1213/ANE.0000000000000693