Journal of neurotrauma
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Journal of neurotrauma · Aug 2009
Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis.
Traumatic brain injury (TBI) can lead to several physiologic complications including gastrointestinal dysfunction. Specifically, TBI can induce an increase in intestinal permeability, which may lead to bacterial translocation, sepsis, and eventually multi-system organ failure. However, the exact mechanism of increased intestinal permeability following TBI is unknown. ⋯ Expression of ZO-1 was decreased by 49% relative to sham animals (p < 0.02), whereas expression of occludin was decreased by 73% relative to sham animals (p < 0.001). An increase in intestinal permeability corresponds with decreased expression of tight junction proteins ZO-1 and occludin following TBI. Expression of intestinal tight junction proteins may be an important factor in gastrointestinal dysfunction following brain injury.
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Journal of neurotrauma · Aug 2009
Conditional knockout of brain-derived neurotrophic factor in the hippocampus increases death of adult-born immature neurons following traumatic brain injury.
It has been reported that the hippocampus is particularly vulnerable to traumatic brain injury (TBI), the consequence of which results in hippocampal-dependent cognitive impairment. In the previous study we found that adult-born immature neurons in the hippocampal dentate gyrus are the most vulnerable cell type to moderate TBI insult. ⋯ The results showed that the amount of adult-born immature neuron death in the hippocampal dentate gyrus significantly increased in the BDNF conditional knockout mice. This result suggests that BDNF is involved in regulating the survival of adult-born immature neurons in the hippocampus following TBI, and potentially might be a useful target for preventing the adult-born immature neurons from death following TBI.
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Journal of neurotrauma · Aug 2009
Temporal and spatial dynamics of peroxynitrite-induced oxidative damage after spinal cord contusion injury.
The reactive nitrogen species peroxynitrite (PN) has been suggested to be an important mediator of the secondary oxidative damage that occurs following acute spinal cord injury (SCI). The PN decomposition products nitrogen dioxide (*NO(2)), hydroxyl radical (*OH), and carbonate radical (*CO(3)) are highly reactive with cellular lipids and proteins. In this immunohistochemical study, we examined the temporal (3, 24, and 72 h, and 1 and 2 weeks) and spatial relationships of PN-mediated oxidative damage in the contusion-injured rat thoracic spinal cord (IH device, 200 kdyn, T10) using 3-nitrotyrosine (3-NT), a marker for protein nitration by PN-derived *NO(2) and 4-hydroxynonenal (4-HNE), an indicator of lipid peroxidation (LP) initiated by any of the PN radicals. ⋯ At all time points except 3 h, there was no significant difference in the mean rostral or caudal extent of 3-NT and 4-HNE staining. By 1, and more so at 2 weeks, the longitudinal extent of the oxidative damage staining was greatly decreased. The spatial and temporal overlap of 3-NT and 4-HNE staining supports the concept that PN is involved in both damage produced by lipid peroxidation and protein nitration, and that antioxidant agents that target PN or PN-derived radicals should be effective neuroprotectants for acute SCI if administered during the first post-injury hours.
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Journal of neurotrauma · Aug 2009
P43/pro-EMAPII: a potential biomarker for discriminating traumatic versus ischemic brain injury.
To gain additional insights into the pathogenic cellular and molecular mechanisms underlying different types of brain injury (e.g., trauma versus ischemia), recently attention has focused on the discovery and study of protein biomarkers. In previous studies, using a high-throughput immunoblotting (HTPI) technique, we reported changes in 29 out of 998 proteins following acute injuries to the rat brain (penetrating traumatic versus focal ischemic). Importantly, we discovered that one protein, endothelial monocyte-activating polypeptide II precursor (p43/pro-EMAPII), was differentially expressed between these two types of brain injury. ⋯ Changes in protein expression were assessed by Western blot analysis and immunohistochemistry. Our results indicated that p43/pro-EMAPII was significantly increased in brain tissues, CSF, and plasma following PBBI, but decreased after MCAo injury compared to their respective sham control samples. This differential expression of p43/pro-EMAPII may be a useful injury-specific biomarker associated with the underlying pathologies of traumatic versus ischemic brain injury, and provide valuable information for directing injury-specific therapeutics.
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Journal of neurotrauma · Aug 2009
Randomized Controlled TrialResuscitation with hypertonic saline-dextran reduces serum biomarker levels and correlates with outcome in severe traumatic brain injury patients.
In the treatment of severe traumatic brain injury (TBI), the choice of fluid and osmotherapy is important. There are practical and theoretical advantages to the use of hypertonic saline. S100B, neuron-specific enolase (NSE), and myelin-basic protein (MBP) are commonly assessed biomarkers of brain injury with potential utility as diagnostic and prognostic indicators of outcome after TBI, but they have not previously been studied in the context of fluid resuscitation. ⋯ HSD-resuscitated patients with favorable outcomes exhibited the lowest serum S100B and NSE concentrations, while maximal levels were found in NS-treated patients with unfavorable outcomes. The lowest biomarker levels were seen in survivors resuscitated with HSD, while maximal levels were in NS-resuscitated patients with fatal outcome. Pre-hospital resuscitation with HSD is associated with a reduction in serum S100B, NSE, and MBP concentrations, which are correlated with better outcome after severe TBI.