Table 3.
Systemic Hypothermia
| Paper | Animal model and injury model | Intervention and timing | Experimental groups |
Reported outcomes: • behavioral • Histologic/biochemical/physiological |
|---|---|---|---|---|
| Lo J Comp Neurol2009 |
Model: Adult Female Fischer Rats, 180–200 g Injury: C5 OSU Impactor displacement of 0.95 mm |
Hypothermia • 33°C @ 5 min PI for 4 h with gradual rewarming (1°C per hour) |
SCI + • Hypothermia (n = 13) • Normothermia (n = 14) Uninjured control (n = 15) |
Histologic/Biochemical/Physiological: Hypothermia spared gray and white matter • Decreased the loss of ventral motor neurons (NeuN+) at 0.9-1.5 mm from the epicenter, but not in the epicenter. • The loss of retrogradely traced neurons is significantly retarded (28.1% vs 61.2%) • Hypothermia caused no significant changes in physiological variables. Behavioral: Improved forelimb strength (weight-supported hanging and grip strength). No difference in the incline plane. Significant improvement in BBB scores only during weeks 1–3, but not at 8w PI. |
| Duz Neurochem Res2009 |
Model: female Wister Rats, 250–350 g Injury: T9 clip compression 50 g × 60 sec |
Hypothermia • 27–29oC @ 5 min PI for 1 h |
SCI + • Hypothermia (n = 7 + 7) • Normothermia (n = 7 + 7) Sham (n = 7) Tissue harvested 1 h or 24 h PI |
Histologic/Biochemical/Physiological: 1 h hypothermia reduced lipid peroxidation (thiobarbituric acid reaction) and GSH-peroxidase levels. This beneficial effect reversed at 24h following systemic hypothermic treatment. Behavioral: Not reported. |
| Morino Spinal Cord2008 |
Model: Adult Male SD Rats, 200–300 g Injury: T11 clip compression 20 g × 20 min |
Hypothermia • 33oC @ 0 h from beginning of compression for 1 h |
SCI + • Hypothermia (n = 5 for behaviour, n = 15 for histology) • Normothermia (n = 5 for behaviour, n = 14 for histology) Sham (n = 8) |
Histologic/Biochemical/Physiological: 1 h hypothermia significantly decreased microglia (isolectin-positive cells) at 48 and 72h PI. Marked but not significant dcrease in the TNF-α in the compressed portion of the spinal cord was observed during this period of time. Behavioral: Motor function measured as standing frequency returned to the normal levels at 72h PI in the hypothermic rats, while no improvement was observed in the normothermic rats. |
| Strain Dig Dis Sci2005 |
Model: Adult Male SD Rats, 300–500 g Injury: C6-7 transection |
Hypothermia • 23.8 ± 0.9°C • 19.4 ± 0.7°C cooling started @ 0 h PI and target temperature reached @ 6 h PI |
SCI + • Hypothermia 23.8°C (n = 12) • Hypothermia 19.4°C (n = 12) • Normothermia (n = 12) Sham (n = 12) |
Histologic/Biochemical/Physiological: Hypothermia significantly increased gastric ulcerogenesis compared to euthermia, probably primarily due to decreased circulation, while maintained euthermia produced ulcer indices not different from sham surgery. The mean ulcer index was 1.62 ± 0.96 for Group 1; 2.00 ± 0.71 for Group 2; 0.25 ± 0.45 for Normothermia, 0.09 ± 0.30 for the sham-operated animals. Behavioral: Not reported. |
| Shibuya Spinal Cord2004 |
Model: Male SD Rats, 280–320 g Injury: T11 Compression 25 g × 10 min |
Hypothermia • 32°C, @ 0 h PI for 4 h |
SCI + • Hypothermia • Normothermia Sham n = 15/group SCI n = 9/group Sham |
Histologic/Biochemical/Physiological: At 3 and 7 days post-injury, significantly fewer TUNEL positive cells around injury site with hypothermia. Behavioral: Not reported. |
| Westergren Spinal Cord2001 |
Model: Male SD Rats, 350-420 g Injury: T8 Compression 35 g × 5 min |
Hypothermia • 30°C, @ 15 min PI and maintained during measurements |
SCI + • Hypothermia • Normothermia Sham • Hypothermia • Normothermia n = 6/group |
Histologic/Biochemical/Physiological: Hypothermia reduces spinal cord blood flow (SCBF) compared to normothermic uninjured controls, but in the trauma groups, hypothermia did not significantly reduce SCBF compared to normothermia (11.3% difference, p = 0.09). Behavioral: Not reported. |
| Chatzipanteli J Neurotrauma2000 |
Model: Female SD Rats, 250-300 g Injury: T10 NYU Impactor 10 g × 12.5 mm |
Hypothermia • 32°C, @ 0 h PI for 3 h |
SCI + • Hypothermia • Normothermia Sham • Hypothermia • Normothermia n = 4/group |
Histologic/Biochemical/Physiological: Hypothermia significantly reduces myeloperoxidase activity (a marker of neutrophil accumulation) (143.1 ± 23.4 vs 511.3 ± 39.0) Behavioral: Not reported. |
| Jou Spine2000 |
Model: SD rats, 290-340 g Injury: C6/7 Clip Compression 10 or 60 s |
Hypothermia • 34°C, PRIOR Injury for 1 h • 30°C, PRIOR Injury for 1 h |
SCI + • Hypothermia • Normothermic n = 12/group |
Histologic/Biochemical/Physiological: Moderate hypothermia resulted in less gross tissue destruction at injury epicenter. Behavioral: Moderate hypothermia improved neurophysiological recordings during cord compression, and improved hindlimb motor function 3 days post-injury with moderate hypothermia. |
| Westergren Acta Neurochir2000 |
Model: Male SD Rats, 350-500 g Injury: T8 Compression 35 g × 5 min |
Hypothermia • 30°C, @ 0 h PI for 2 h |
SCI + • Hypothermia (n = 14) • Normothermia (n = 12) Sham • Hypothermia (n = 4) |
Histologic/Biochemical/Physiological: Not reported. Behavioral: No improvement in hindlimb motor scores or inclined plane performance in hypothermic animals at 2 weeks post-injury. |
| W.R. Yu Acta Neuropathol2000 a |
Model: Male SD Rats, 387 ± 37 g Injury: T8 Compression 35 g × 5 min |
Hypothermia • 30°C, @ 0 h PI for 20 min |
SCI + • Hypothermia • Normothermia Sham • Hypothermia n = 5/group |
Histologic/Biochemical/Physiological: 24 h PI, significantly larger cord cross sectional area in normothermic SCI animals compared to hypothermia SCI and sham animals (suggestive of reduced edema in hypothermia). Microtubule-associated protein 2 (MAP2) immunostaining was significantly less in normothermia animals at injury site. Behavioral: Not reported. |
| C.G. Yu J Neurosurg Spine2000b |
Model: Female SD Rats, 225-275 g Injury: T10 NYU Impactor 10 g × 12.5 mm |
Hypothermia • 32-33°C, @ 30 min PI for 4 h |
SCI + • Hypothermia (n = 19) • Normothermia (n = 17) |
Histologic/Biochemical/Physiological: 16 longitudinal sections through injured cord 6 weeks postinjury revealed decreased lesion size (15.8% difference, p < 0.01). Behavioral: BBB scores in hypothermia animals were significantly better by 9 days post-injury and then thereafter, including the final 6 week evaluation (13.3 ± 0.5 vs 10.8 ± 0.4, p = 0.0024). |
| Westergren Spinal Cord1999 |
Model: Male SD Rats, 387 ± 37 g Injury: T8 Compression 50 g × 5 min |
Hypothermia • 30°C, @ 0 h PI for 20 min |
SCI + • Hypothermia • Normothermia Sham • Hypothermia n = 5/group |
Histologic/Biochemical/Physiological: Semi-quantitative analysis around the injury site revealed decreased b-APP, ubiquitin, and PGP9.5 in hypothermia animals. Behavioral: Not reported. |
| Yu Acta Neuropathol1999 a |
Model: Male SD Rats, 387 ± 37g Injury: T8 Compression 50 g × 5 min |
Hypothermia • 30°C, @ 0h PI for 20min |
SCI + • Hypothermia • Normothermia Sham • Hypothermia n = 5/group |
Histologic/Biochemical/Physiological: Semi-quantitative analysis of albumin, fibrinogen, and fibronectin shows decreases in all three in hypothermia-treated animals, suggesting that there is less vasogenic edema; cord cross sectional area was also reduced (suggestive again of decreased edema). Behavioral: Not reported. |
| Yu Neuropatho1999 b |
Model: Male SD Rats, 387 ± 37 g Injury: T8 Compression 50 g × 5 min |
Hypothermia • 30°C, @ 0h PI for 20min |
SCI + • Hypothermia • Normothermia Sham • Hypothermia n = 5/group |
Histologic/Biochemical/Physiological: Semi-quantitative analysis around the injury site revealed decreased vimentin in capillaries and decreased GFAP. Behavioral: Not reported. |
| Yamamoto Neuroreport1998 |
Model: Male SD Rats, 350-375 g Injury: L1 Epidural Balloon Compression 60 s |
Hypothermia • 33°C, PRIOR Injury for 4h |
SCI + • Hypothermia + Nicaraven (n = 5) • Hypothermia (n = 5) • Nicaraven (n = 12) • Normothermia (n = 5) |
Histologic/Biochemical/Physiological: Microdialysis revealed significantly lower CSF glutamate levels in hypothermia-treated animals compared to normothermic controls, with no additional benefit with Nicaraven (free radical scavenger). Behavioral: Not reported. |
| Farooque J Neurotrauma1997 |
Model: Male SD Rats Injury: T8 Severe Cord Compression |
Hypothermia • 30-31°C, PRIOR injury and then during entire observation period |
SCI + • Hypothermia • Normothermia n = 6/group |
Histologic/Biochemical/Physiological: Microdialysis revealed no significant difference in lactate levels in hypothermia animals, and they had (surprisingly) increased extracellular levels of glutamate and aspartate compared to normothermic animals. Behavioral: Not reported. |
| Martinez-Arizala J Neurotrauma1992 |
Model: Female SD Rats, 250-300 g Injury: T8 Weight Drop 50 g × cm |
Hypothermia • 31-32°C, PRIOR injury for 4 h |
SCI + • Hypothermia • Normothermia n = 3/group |
Histologic/Biochemical/Physiological: Hypothermia-treated animals had less hemorrhage and parenchymal damage than controls, but no description is provided about how this was analyzed or quantified. Behavioral: All animals remained completely paralyzed during the 4d observation period (no functional benefit reported with hypothermia). |
SCI: spinal cord injury; d: day, days; h: hour, hours; w: week, weeks; PI: post-injury
T8: thoracic vertebra 8; C5: cervical vertebra 5
BBB: Basso, Beattie and Bresnahan locomotor test; CSF: cerebrospinal fluid; GFAP: glial fibrillary acidic protein; SD rats: Sprague-Dawley rats; TNF: tumor necrosis factor.