Neuroprotective assessment of prolonged local hypothermia post contusive spinal cord injury in rodent model

Abstract

Background context: Although general hypothermia is recognized as a clinically applicable neuroprotective intervention, acute moderate local hypothermia post contusive spinal cord injury (SCI) is being considered a more effective approach. Previously, we have investigated the feasibility and safety of inducing prolonged local hypothermia in the central nervous system of a rodent model.

Purpose: Here, we aimed to verify the efficacy and neuroprotective effects of 5 and 8 hours of local moderate hypothermia (30±0.5°C) induced 2 hours after moderate thoracic contusive SCI in rats.

Study design: Rats were induced with moderate SCI (12.5 mm) at its T8 section. Local hypothermia (30±0.5°C) was induced 2 hours after injury induction with an M-shaped copper tube with flow of cold water (12°C), from the T6 to the T10 region. Experiment groups were divided into 5-hour and 8-hour hypothermia treatment groups, respectively, whereas the normothermia control group underwent no hypothermia treatment.

Methods: The neuroprotective effects were assessed through objective weekly somatosensory evoked potential (SSEP) and motor behavior (basso, beattie and bresnahan Basso, Beattie and Bresnahan (BBB) scoring) monitoring. Histology on spinal cord was performed until at the end of day 56. All authors declared no conflict of interest. This work was supported by the Singapore Institute for Neurotechnology Seed Fund (R-175-000-121-733), National University of Singapore, Ministry of Education, Tier 1 (R-172-000-414-112.).

Results: Our results show significant SSEP amplitudes recovery in local hypothermia groups starting from day 14 post-injury onward for the 8-hour treatment group, which persisted up to days 28 and 42, whereas the 5-hour group showed significant improvement only at day 42. The functional improvement plateaued after day 42 as compared with control group of SCI with normothermia. This was supported by both 5-hour and 8-hour improvement in locomotion as measured by BBB scores. Local hypothermia also observed insignificant changes in its SSEP latency, as compared with the control. In addition, 5- and 8-hour hypothermia rats' spinal cord showed higher percentage of parenchyma preservation.

Conclusions: Early local moderate hypothermia can be induced for extended periods of time post SCI in the rodent model. Such intervention improves functional electrophysiological outcome and motor behavior recovery for a long time, lasting until 8 weeks.

Keywords: Electrophysiology; Induced hypothermia; Local Hypothermia; Motor activity; Rodent Spinal Cord Injury; Somatosensory evoked potentials; Spinal cord contusion.