Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats

Abstract

Hypothermia has been employed during the past 30 years as a therapeutic modality for spinal cord injury (SCI) in animal models and in humans. With our newly developed rat cervical model of contusive SCI, we investigated the therapeutic efficacy of transient systemic hypothermia (beginning 5 minutes post-injury for 4 hours, 33 degrees C) with gradual rewarming (1 degrees C per hour) for the preservation of tissue and the prevention of injury-induced functional loss. A moderate cervical displacement SCI was performed in female Fischer rats, and behavior was assessed for 8 weeks. Histologically, the application of hypothermia after SCI resulted in significant increases in normal-appearing white matter (31% increase) and gray matter (38% increase) volumes, greater preservation (four-fold) of neurons immediately rostral and caudal to the injury epicenter, and enhanced sparing of axonal connections from retrogradely traced reticulospinal neurons (127% increase) compared with normothermic controls. Functionally, a faster rate of recovery in open field locomotor ability (BBB score, weeks 1-3) and improved forelimb strength, as measured by both weight-supported hanging (43% increase) and grip strength (25% increase), were obtained after hypothermia. The current study demonstrates that mild systemic hypothermia is effective for retarding tissue damage and reducing neurological deficits following a clinically relevant contusive cervical SCI.

Protection in Animal Models of Brain and Spinal Cord Injury with Mild to Moderate Hypothermia

“…Most recently, mild hypothermia has also been used to target cervical SCI, a commonly seen clinical problem. In a recent study by Lo et al (2009), improved forelimb function as well as preservation of motor neurons and decreased contusion volume was seen in rats cooled after a cervical traumatic insult. Taken together, these studies show that mild to moderate hypothermia improves outcome in models of both thoracic and cervical SCI.…”

Hypothermic Treatment for Acute Spinal Cord Injury

“…In an attempt to determine whether therapeutic hypothermia would help following severe cervical SCI, an animal model of SCI was developed [70]. In a study by Lo et al [22], moderate hypothermia introduced after cervical SCI again led to improved behavioral and histopathological outcomes. Following cervical trauma, hypothermia was introduced by reducing the core temperature to 33°for a 4-h period followed by slow rewarming.…”

“…**p<0.01 compared with normothermic controls; ***p<0.001. (Reprinted with permission from Lo et al [22]). …”

“…However, more recently, the beneficial effects of more modest levels of hypothermia has been appreciated [7,[20][21][22][23][24][25]. In the 1980s, studies showed for the first time that relatively small reductions in brain tissue temperature provided significant protection against ischemic and traumatic neuronal cell death [7].…”

“…In terms of SCI, published data have shown that relatively mild levels of hypothermia introduced after a traumatic or compressive SCI provides some degree of improvement in function and reduces the histopathological damage [22,[25][26][27][28][29][30][31][32][33][34][35][36][37]. In clinically relevant SCI studies, mild reductions in temperature have been shown to be protective, whereas mild elevations (hyperthermia) have been reported to worsen outcome [38][39][40].…”