Table 1.
Data overview of 24 animal studies utilizing hypothermia as therapy after TSCI [5,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,38,39,40,41,42]. NR = not reported; BBB = Basso–Beattie–Bresnahan locomotor rating scale.
| Study | Animal | Injury Method | Level of Injury | Hypothermia Method | Treatment Temp/Rate | Target Temp | Treatment Onset | Duration | Other Therapy | Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|
| Albin et al., 1968 | Rhesus monkeys (n = 14) | Weight drop (300 g/cf) | T10 | Local: subarachnoid heat exchanger | 2–5 °C | 10 °C | 4 h after injury | 3 h | None | No deleterious effects were noted. 13 of 14 treated monkeys achieved complete functional recovery. |
| Barbosa et al., 2014 | Wistar rats (n = 15 per group) | NYU impactor (25 g/fc) | T9–10 | Local: epidural cold solution perfusion | 9–10 °C | 25 °C | Immediately after injury | 20 min | None | No difference in motor outcomes (BBB) were seen between groups. |
| Batchelor et al., 2010 | Female Fischer rats (n = 16 per group) | Spinal cord impactor (150 kdyn) and canal spacer | T8 | Systemic: surface cooling | NR | 33 °C | 30 min after injury | 7.5 h | Spacer decompression (0, 2, or 8 h after injury) | Hypothermia significantly improved (p < 0.005) BBB and ladder-stepping scores in rats decompressed after 8 h. |
| Casas et al., 2005 | Female Sprague-Dawley rats (n = 14 per group) | NYU impactor (12.5 g·cm) | T10 | Local: epidural saline perfusion | 4 °C | 20, 30, or 37.5 °C | 30 min after injury | 3 h | None | No differences in motor outcomes (BBB) were observed between groups. |
| Dimar et al., 2000 | Male Sprague-Dawley rats (n = 8 per group) | NYU impactor (25 g·cm), 50% canal spacer, or both | T10 | Local: epidural cooling apparatus | 19 °C | NR | Immediately after injury | 2 h | Spacer decompression (2 h after insertion) | Hypothermia significantly (p < 0.05) improved motor (BBB) outcomes in the spacer-only group at 5 weeks post-injury. |
| Grulova et al., 2013 | Male Wistar rats (n > 11 per group) | Balloon catheter compression | T8–9 | Systemic: surface cooling | NR | 31–32 °C | Immediately after injury | 30 min | None | Hypothermia improved (p < 0.01) urinary scores within 5 days of injury. No difference in motor (BBB) outcomes was observed. |
| Ha et al., 2008 | Male Sprague-Dawley rats (n = 8 per group) | NYU impactor (25 g·cm) | T9 | Local: epidural saline perfusion | 18 °C | 30 °C | Immediately after injury | 48 h | None | Hypothermia improved (p < 0.01) motor function (Gale) and incline plane scores 7 days after injury. |
| Hosier et al., 2015 | Female Long-Evans rats (n > 7 per group) | Spinal cord impactor (25 g·cm) | C8; left unilateral | Systemic: surface cooling | −8 °C/h | 33 °C | 5 min after injury | 4 h | None | Hypothermia improved (p < 0.05) motor scores 7 days after injury. Beam balance, accelerating rotarod, and BBB scores were greater (p < 0.05) in the hypothermia group 6 weeks after injury. |
| Jorge et al., 2019 | Female Sprague-Dawley rats (n > 5 per group) | Spinal cord impactor (200 kdyn) | T8 | Systemic: surface cooling | NR | 32 °C | Beginning of surgery | 2 h | None | Hypothermia-treated rats had significantly higher (p < 0.01) BBB scores 6 weeks after injury. |
| Kao et al., 2011 | Male Sprague-Dawley rats (n = 8 per group) | Aneurysm clip (55 g) | T8–9 | Systemic: surface cooling | 31 °C | 33 °C | Immediately after injury | 2 h | None | Hypothermia group had significantly higher (p < 0.05) BBB scores 4 days after injury. |
| Karamouzian et al., 2015 | Male Wistar rats (n = 20 per group) | Weight drop (25 g·cm) | T8–9 | Systemic: surface cooling | NR | 33–34 °C | 30 min (early) or 3.5 h (late) after injury | 3 h | Methylprednisolone (30 mg/kg immediately after injury) | Groups treated with early/late hypothermia, methylprednisolone, or both achieved significantly higher (p = 0.05) BBB scores than controls 2–3 weeks after injury. No motor differences were seen among treatment groups. |
| Kuchner et al., 2000 | Female mongrel dogs (n > 15 per group) | Epidural balloon inflation (160 mm·Hg) | T13 | Local: epidural heat exchanger | NR | 3–9 °C | 15 min (hypothermia only) or 3.5 h (hypothermia and dexamethasone) after Injury | 4 h | Dexamethasone (0.24 mg/kg/day) | Hypothermia (p < 0.05), steroid (p < 0.05), and dual-therapy (p < 0.01) groups had significantly higher motor scores compared to controls at 7 weeks post-injury. |
| Lo et al., 2009 | Female Fischer rats (n = 15 per group) | OSU electromagnetic SCI device (3 kdyn) | C5 | Systemic: surface cooling | NR | 33 °C | After injury | 4 h | None | Hypothermia did not improve BBB or incline plane test scores. Hypothermia significantly increased forelimb gripping (p < 0.05) and self-supported hanging (p < 0.01) 8 weeks after injury |
| Maybhate et al., 2012 | Female Lewis rats (n = 10 per group) | NYU impactor (12.5 g·cm) | T8 | Systemic: surface cooling | NR | 32 °C | 2 h after injury | 2 h | None | Hypothermia significantly improved (p < 0.00004) BBB scores at 4 weeks post-injury. |
| Morizane et al., 2012 | Female Wistar rats (n > 8 per group) | NYU impactor (25 g·cm) | T4 | Local: extracorpeal thermoelectric cooling device | NR | 33 °C | Immediately after injury | 48 h | None | Hypothermia-treated rats had significantly better (p < 0.01) BBB scores at 8 weeks post-injury |
| Morochovic et al., 2008 | Male Sprague-Dawley rats (n = 10 per group) | Epidural balloon catheter | T8–9 | Local: surface cooling | −1.4 °C/min | 30 °C | 25 min after injury | 60 min | None | No difference in locomotor performance (BBB) was detected between groups. |
| Ok et al., 2012 | Male Sprague-Dawley rats (n = 8 per group) | NYU impactor (25 g·cm) | T9 | A. Local: epidural water infusion B. Systemic: cold air chamber |
A. 20 °C B. −0.25 °C/min |
A. 28 °C B. 32 °C | A. After injury B. After waking from anesthesia | 48 h | None | 6 weeks after SCI, both local and systemic hypothermia groups had significantly higher (p < 0.05) BBB scores. |
| Seo et al., 2015 | Male Sprague-Dawley rats (n = 27 per group) | NYU impactor (25 g·cm) | T9 | Systemic: surface cooling | NR | 30–32 °C | After injury | 4 h | None | 6 weeks after SCI, hypothermia groups had significantly better (p < 0.05) BBB scores than control. |
| Tator et al., 1973 | Rhesus monkeys (n = 10 per group) | Inflatable cuff (350–400·mm Hg) | T9 | Local: subarachnoid cold solution perfusion | 5 °C | NR | 3 h after injury and immediately after durotomy | 3 h | Durotomy (immediately before hypothermia) | Normothermia-durotomy group recovered significantly better than nonperfused no durotomy group after 400 mm·Hg injury. Hypothermia treatment did not have this effect. |
| Teh et al., 2018 | Sprague-Dawley rats (n = 7 per group) | NYU impactor (12.5 g·cm) | T8 | Local: epidural heat exchange | −0.5 °C/min | 30 °C | 2 h after injury | 5 or 8 h | None | BBB scores were significantly higher in both 5 h (p = 0.001) and 8 h (p = 0.006) hypothermia groups compared to control after 6 weeks. |
| Thienprasit et al., 1975 | Adult cats (n > 5 per group) | Balloon catheter inflation | L2 | Local: epidural saline perfusion | 15 °C | NR | 6 h after injury | 2 h | Decompressive laminectomy (6 h after injury but before cooling) | Animals whose cortical-evoked responses failed to reappear within 6 h of injury had significantly better recovery (p < 0.01) after hypothermia and laminectomy compared to laminectomy alone. |
| Westergren et al., 2000 | Male Sprague-Dawley rats (n > 5 per group) | Blocking weight technique (50 g) | T7–8 | Systemic: surface cooling | NR | 30 °C | After injury | 2 h | None | Animals treated with hypothermia performed better on inclined plane test at 2 weeks post-injury. No differences in motor function (Gale) scores were detected. |
| Xu et al., 2016 | Male Sprague-Dawley rats (n = 7 per group) | Aneurysm clip (10 g) | T10 | Local: epidural saline infusion | 4 °C | 18 °C | Immediately after injury | 2 h | None | Hypothermia group achieved significantly higher (p < 0.05) BBB scores than control up to 3 weeks after injury. |
| Yu et al., 2000 | Female Sprague-Dawley rats (n > 7 per group) | NYU impactor (12.5 g·cm) | T10 | Systemic: surface cooling | NR | 32 °C | 30 min after injury | 4 h | None | BBB scores were significantly higher (p = 0.0024) 6 weeks after injury in hypothermia group compared to normothermia. |