Journal of neurotrauma
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Journal of neurotrauma · Apr 2013
Effects of topical administration of nimodipine on cerebral blood flow following subarachnoid hemorrhage in pigs.
We sought to explore whether topical administration of nimodipine improves the abnormal cerebral perfusion following subarachnoid hemorrhage (SAH) in pigs. Fourteen pigs were randomly divided into three groups: sham (n=4), SAH (n=5), or SAH + nimodipine (n=5). The SAH model was established by injecting fresh autologous nonheparinized arterial blood into the suprasellae cistern. ⋯ Topical administration of nimodipine did not significantly improve CBF following SAH. These findings were not consistent with our previous data demonstrating that the topical administration of nimodipine significantly alleviates cerebral vasospasm following SAH detected by TCD. Potential mechanisms governing these disparate outcomes require further investigation.
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Journal of neurotrauma · Apr 2013
Monitoring functional impairment and recovery after traumatic brain injury in rats by FMRI.
The present study was designed to test a hypothesis that functional magnetic resonance imaging (fMRI) can be used to monitor functional impairment and recovery after moderate experimental traumatic brain injury (TBI). Moderate TBI was induced by lateral fluid percussion injury in adult rats. The severity of brain damage and functional recovery in the primary somatosensory cortex (S1) was monitored for up to 56 days using fMRI, cerebral blood flow (CBF) by arterial spin labeling, local field potential measurements (LFP), behavioral assessment, and histology. ⋯ This is, to our knowledge, the first study demonstrating that fMRI can be used to monitor post-TBI functional impairment and consequent spontaneous recovery. Moreover, the BOLD response was associated with the density of myelinated fibers in the S1, rather than with neurodegeneration. The present findings encourage exploration of the usefulness of fMRI as a noninvasive prognostic biomarker for human post-TBI outcomes and therapy responses.
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Journal of neurotrauma · Apr 2013
Poloxamer 188 attenuates in vitro traumatic brain injury-induced mitochondrial and lysosomal membrane permeabilization damage in cultured primary neurons.
Acute membrane damage due to traumatic brain injury (TBI) is a critical precipitating event. However, the subsequent effects of the mechanical trauma, including mitochondrial and lysosomal membrane permeability (MOMP and LMP) remain elusive. The main objective of the current study was to assess the role of a putative membrane-resealing agent poloxamer 188 (P188) in MOMP and LMP in response to a well-defined mechanical insult. ⋯ Both P188 and CBI treatment decreased the cytosolic accumulation of tBid in supernatant of purified lysosomes, and the amount of mitochondrial localized tBid. These data indicate injured neurons have undergone mitochondrial and lysosomal membrane permeability damage, and the mechanism can be exploited with pharmacological interventions. P188's neuroprotection appears to involve a relationship between cathepsin B and tBid-mediated mitochondrial initiation of cell death.
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Journal of neurotrauma · Apr 2013
Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury.
2-arachidonylglycerol (2-AG) is the most abundant endocannabinoid in the central nervous system and is elevated after brain injury. Because of its rapid hydrolysis, however, the compensatory and neuroprotective effect of 2-AG is short-lived. Although inhibition of monoacylglycerol lipase, a principal enzyme for 2-AG degradation, causes a robust increase of brain levels of 2-AG, it also leads to cannabinoid receptor desensitization and behavioral tolerance. ⋯ The blood-brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced. Furthermore, the beneficial effects of WWL70 involved up-regulation and activation of cannabinoid type 1 and type 2 receptors and were attributable to the phosphorylation of the extracellular signal regulated kinase and the serine/threonine protein kinase AKT. This study indicates that the fine-tuning of 2-AG signaling by modulating ABHD6 activity can exert anti-inflammatory and neuroprotective effects in TBI.
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Journal of neurotrauma · Mar 2013
The effect of cigarette smoke exposure on spinal cord injury in rats.
In this study, we examined whether cigarette smoke has neuroprotective or toxic effects on spinal cord injury (SCI). Male Sprague-Dawley rats were included in the study and received either cigarette smoke exposure or fresh air exposure. Twenty-four hours after the last cigarette smoke or fresh air exposure, all rats were injured at thoracic level 12 (T12), using an established static compression model. ⋯ These results suggested that cigarette smoke can reinforce the oxidative stress injury via HIF-1α and AQP4 in the early stage after SCI. It is possible that cigarette smoke exposure does not affect SCI recovery in the long term; however, it can aggravate the edema and deteriorate BSCB disruption via HIF-1α and AQP4 in the early stage after SCI. More studies will be essential to consider this hypothesis and elucidate the mechanisms involved.