Protective Effects of Moderate Hypothermia on Behavioral Deficits But Not Necrotic Cavitation Following Cortical Impact Injury in the Rat

Abstract

A number of experimental studies have reported that moderate hypothermia can produce significant protection against behavioral deficits and/or morphopathological alterations following traumatic brain injury; a Phase 3 clinical trial is currently examining the therapeutic potential for moderate hypothermia (32 degrees C) to improve outcome following severe traumatic brain injury in humans. The current study examined whether hypothermia (32 degrees C) provided behavioral protection following experimental cortical impact injury. The extent of focal cortical contusion was also examined in the same rats. A total of 30 male Sprague-Dawley rats were trained on beam balance and beam walking tasks prior to injury. Under isoflurane anesthesia, cortical impact was produced on the right parietal cortex of 20 rats. Ten rats underwent all surgical procedures but were not impacted (sham-injured rats). Ten of the injured rats were cooled to 32 degrees C (measured in temporalis muscle) beginning 5 min postinjury, maintained for 2 h and rewarmed slowly for 1 h. In the other 10 injured rats, normothermic temperatures (37.5 degrees C) were maintained for the same duration. Beam balance and beam walking performance was assessed daily for 5 days following injury. At 11 days postinjury, rats were assessed for 5 days on acquisition of the Morris water maze task. Following behavioral assessments, rats were perfused and the brain removed. Coronal sections were cut through the site of cortical impact injury and stained with hematoxylin and eosin. Hypothermic treatment resulted in significantly less beam balance and beam walking deficits than observed in normothermic rats. Hypothermia also significantly attenuated spatial memory performance deficits. Quantitative morphometric analyses failed to detect any significant differences in volumes of necrotic tissue cavitation in cortices of hypothermic and normothermic rats. Hypothermic treatment also had no effect on volumes of dorsal hippocampal tissue or numbers of cells in CA1 or CA3 regions of the hippocampus. These data suggest that hypothermia, consistent with the reports of others, can produce significant behavioral protection following cortical impact injury that is not necessarily correlated with changes in focal cortical necrosis within the first 15 days following injury.

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

“…This discrepancy in the time course of SBC neuroprotection measured for histopathology versus neurobehavioral deficits is intriguing, but not necessarily counterintuitive. Studies of brain trauma and ischemia have repeatedly shown that neurofunctional recovery may involve integrated compensatory abilities of the brain in the absence of focal neuronal survival (Dixon et al, 1998;Lu et al, 2009). In this study, the protective effects of SBC on acute postinjury FIG.…”

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

“…Experimental and clinical efforts aimed at treating this significant health care issue have resulted in numerous therapeutic approaches such as, but not limited to, anti-inflammatory and anti-oxidative strategies [4,34,36,39,51,56,101], hypothermia [5,9,13,14,21,57], and the exogenous administration of neurotrophins [19,84,88]. Another line of research that has received significant attention as a potential treatment strategy is the administration of various pharmacologic agents targeting both specific and non-specific neurotransmitter systems in an attempt to restore neural activity that has been altered by TBI [2,25,44,[51][52][53][54][55].…”

Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

“…[9][10][11][12][13][14] Several clinical and experimental studies have shown the neuroprotective effects of mild-to-moderate hypothermia, including inhibition of neurological injury, reduction of infarct size, and improvement of neurological outcome. [15][16][17][18] In our previous studies, we found that post-traumatic moderate hypothermia significantly attenuated cell death within the hippocampus after fluid percussion TBI. 3 However, precise mechanisms underlying this phenomenon are still unclear.…”