Journal of neurotrauma
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Journal of neurotrauma · Jan 2009
Hyperbaric oxygen preconditioning attenuates early apoptosis after spinal cord ischemia in rats.
This study tested the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning (HBO-PC) is mediated by inhibition of early apoptosis. Male Sprague-Dawley rats were preconditioned with consecutive 4 cycles of 1-h HBO exposures (2.5 atmospheres absolute [ATA], 100% O(2)) at a 12-h interval. At 24 h after the last HBO pretreatment, rats underwent 9 min of spinal cord ischemia induced by occlusion of the descending thoracic aorta in combination with systemic hypotension (40 mmHg). ⋯ L-nitroarginine-methyl-ester (L-NAME; 10 mg/kg), a nonselective NO synthase (NOS) inhibitor, applied before each HBO-PC protocol abolished these beneficial effects of HBO-PC. We conclude that HBO-PC reduced spinal cord ischemia-reperfusion injury by increasing Mn-SOD, catalase, and Bcl-2, and by suppressing mitochondrial apoptosis pathway. NO may be involved in this neuroprotection.
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Journal of neurotrauma · Jan 2009
NNZ-2566, a glypromate analog, improves functional recovery and attenuates apoptosis and inflammation in a rat model of penetrating ballistic-type brain injury.
Glycine-proline-glutamate (GPE) is an N-terminal tripeptide endogenously cleaved from insulin-like growth factor-1 in the brain and is neuroprotective against hypoxic-ischemic brain injury and neurodegeneration. NNZ-2566 is an analog of GPE designed to have improved bioavailability. In this study, we tested NNZ-2566 in a rat model of penetrating ballistic-type brain injury (PBBI) and assessed its effects on injury-induced histopathology, behavioral deficits, and molecular and cellular events associated with inflammation and apoptosis. ⋯ Although gross lesion volume was not affected, NNZ-2566 treatment significantly attenuated neutrophil infiltration and reduced the number of activated microglial cells in the peri-lesion regions of the PBBI. PBBI induced a significant upregulation in Bax expression (36%) and a concomitant downregulation in Bcl-2 expression (33%), both of which were significantly reversed by NNZ-2566. Collectively, these results demonstrated that NNZ-2566 treatment promoted functional recovery following PBBI, an effect related to the modulation of injury-induced neural inflammatory and apoptotic mechanisms.
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Journal of neurotrauma · Jan 2009
Ibuprofen enhances recovery from spinal cord injury by limiting tissue loss and stimulating axonal growth.
The GTP-binding protein RhoA regulates microfilament dynamics in many cell types and mediates the inhibition of axonal regeneration by myelin and chondroitin sulfate proteoglycans. Unlike most other nonsteroidal anti-inflammatory drugs, ibuprofen suppresses basal RhoA activity (Zhou et al., 2003). A recent report suggested that ibuprofen promotes corticospinal axon regeneration after spinal cord injury (Fu et al., 2007). ⋯ Ibuprofen increases axonal sprouting from serotonergic raphespinal axons, and from rostral corticospinal fibers in the injured spinal cord, but does not permit caudal corticospinal regeneration after spinal contusion. Treatment of mice with complete spinal cord transection demonstrates long-distance raphespinal axon regeneration in the presence of ibuprofen. Thus, administration of ibuprofen improves the recovery of rats from a clinically relevant spinal cord trauma by protecting tissue, stimulating axonal sprouting, and allowing a minor degree of raphespinal regeneration.
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Journal of neurotrauma · Jan 2009
Role of Nrf2 in protection against traumatic brain injury in mice.
Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in modulating traumatic brain injury (TBI)-induced secondary brain injury. ⋯ This exacerbation of brain injury in Nrf2-deficient mice was associated with increased mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and with decreased mRNA expression and enzymatic activity of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wild-type counterparts after TBI. In combination, these results suggest that Nrf2 plays an important role in protecting TBI-induced secondary brain injury, possibly by regulating inflammatory cytokines and inducing antioxidant and detoxifying enzymes.
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Journal of neurotrauma · Jan 2009
Anatomical and functional outcomes following a precise, graded, dorsal laceration spinal cord injury in C57BL/6 mice.
To study the pathophysiology of spinal cord injury (SCI), we used the LISA-Vibraknife to generate a precise and reproducible dorsal laceration SCI in the mouse. The surgical procedure involved a T9 laminectomy, dural resection, and a spinal cord laceration to a precisely controlled depth. Four dorsal hemisection injuries with lesion depths of 0.5, 0.8, 1.1, and 1.4 mm, as well as normal, sham (laminectomy and dural removal only), and transection controls were examined. ⋯ Quantitative histological examination showed significant differences between the injury groups and insignificant lesion depth variance within each of the groups. Statistically significant differences were additionally found in the amount of ventral spared tissue at the lesion site between the injury groups. This novel, graded, reproducible laceration SCI model can be used in future studies to look more closely at underlying mechanisms that lead to functional deficits following SCI, as well as to determine the efficacy of therapeutic intervention strategies in the injury and recovery processes following SCI.