Hypothermia Attenuates the Loss of Hippocampal Microtubule-Associated Protein 2 (MAP2) following Traumatic Brain Injury

Abstract

Summary: Traumatic brain injury (TBI) produces a tis sue-specific decrease in protein levels of microtubule associated protein 2 (MAP2), an important cross-linking component of the neuronal cytoskeleton. Because mod erate brain hypothermia (30°C) reduces certain neurobe havioral deficits produced by TBI, we examined the effi cacy of moderate hypothermia (30°C) in reversing the TBI-induced loss of MAP2 protein. Naive, sham-injured, and moderate (2.1 atm) fluid percussion-injured rats were assessed for MAP2 protein content 3 h post injury using quantitative immunoreactivity measurements. Parallel groups of sham-injured and fluid percussion-injured ani mals were maintained in moderate hypothermia (30°C), as measured by temporalis muscle temperature, for MAP2 quantitation 3 h post injury. No difference in MAP21eveisModerate hypothermia has proven to be an effec tive strategy in the laboratory for protection of neu rons and neuronal function following CNS injury. Early clinical studies employing moderate whole body hypothermia in patients with stroke and brain injury were abandoned due to lack of standardized laboratory models for study and absence of con trolled trial methodologies. Recent studies employ ing moderate levels of hypothermia have shown ef ficacy in prevention of histological cell loss and diminution of neurological function following global and focal ischemia in rats (Busto et aI., 1987(Busto et aI., , 1989 and gerbils (Clifton et aI., 1989 796was observed between naive and sham-iI1iured normo thermic animals. Hypothermia alone had no effect on sol uble MAP2 levels in sham-injured animals compared with normothermic sham-injured controls (88.0 ± 7.3%; p > 0.10). Fluid percussion injury dramatically reduced MAP21eveis in he normothermic group (44.3 ± 5.9%; p < 0.0005) compared with normothermic sham-injured con trols. No significant reduction of MAP2 was seen in the hypothermic injured group (95.2 ± 4.6%; compared with hypothermic sham-injured controls, p > 0.20). Although it is premature to infer any causal link, the data suggest that the attenuation of injury-induced MAP2 loss by hy pothermia may contribute to its overall neuroprotective action.

Pre-Hospital Hypothermia is Not Associated with Increased Survival After Traumatic Brain Injury

“…Experimental studies of post-traumatic hypothermia suggest a multitude of possible mechanisms for neuroprotection. These include reducing levels of the excitatory amino acid glutamate; decreasing abnormal blood-brain barrier permeability after traumatic and ischemic insults; inhibiting diffuse axonal injury; reducing proinflammatory cytokines interleukin 1-b and tumor necrosis factor-a; inhibiting apoptotic cell death by decreasing both cytochrome c release from dysfunctional mitochondria as well as levels of caspase, a significant initiator of apoptosis [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Additionally, TBI is often characterized by a postinjury catecholamine surge that correlates directly with the severity of brain injury [31][32][33].…”

Effects of Hypothermia on Blood Flow and Neural Activity in Rabbit Spinal Cord during Postischemic Reperfusion.

“…It is known that hypothermia decreases metabolic activity [30], prevents ATP degradation [31], reduces glutamate release [32], inhibits protease activation [33], and decreases hydroxyl radical formation [1]. The degradation of ATP may cause intracellular edema through an impairment of Na-K exchange, glutamate release may increase intracellular calcium to a toxic level by activation of NMDA receptors, and hydroxyl radical formation may impair the cellular membrane of the spinal neurons.…”

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

“…Brain injury results in the breakdown of the cytoskeletal proteins microtubule-associated protein 2 (MAP2) and betaactin, which is reversed by hypothermia (Miyazawa et al, 1993;Taft et al, 1993;Wu et al, 1995;Haranishi et al, 2005). This effect is most likely mediated by inhibiting calpain activity, a calcium-dependent protease (Liebetrau et al, 2004).…”