Journal of neurotrauma
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Estrogen plays an important role as a neuroprotector in the central nervous system (CNS), directly interacting with neurons and regulating physiological properties of non-neuronal cells. Here we evaluated estrogen sulfate (E2-SO4) for traumatic brain injury (TBI) using a Sprague-Dawley rat model. TBI was induced via lateral fluid percussion (LFP) at 24 h after craniectomy. ⋯ The edema size in the brains of the E2-SO4 treated group was also significantly smaller than that of vehicle-treated group at 1 day after E2-SO4 injection (p=0.04), and cerebral glycolysis of injured region was also increased significantly during the same time period (p=0.04). However, E2-SO4 treatment did not affect DAI (p>0.05). These findings demonstrated the potential benefits of E2-SO4 in TBI.
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Journal of neurotrauma · Aug 2015
Acute Temporal Profiles of serum levels of UCH-L1 and GFAP and Relationships to Neuronal and Astroglial Pathology Following Traumatic Brain Injury in Rats.
A number of potential traumatic brain injury (TBI) biomarkers have been proposed and evaluated in the laboratory and clinic. This study investigated the temporal profile of circulating biomarkers of astrocytic and neuronal injury over the first 24 h and relevant histopathological changes after experimental moderate TBI. Twenty male rats were randomly assigned to either moderate parasagittal fluid percussion or sham injury. ⋯ Histology revealed characteristic acute neuronal degeneration in the ipsilateral hippocampus and parietal cortex and reduction in GFAP immunostaining in areas of neuronal cell loss. The data provide evidence of a causal relationship between TBI-induced acute brain pathology and circulating neuronal and glial markers, further demonstrating their role as candidate markers for TBI. Studies of relative changes in biomarker levels in CSF and serum suggest that different mechanisms may underlie the transport and/or clearance of UCH-L1 and GFAP in these two compartments.
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Neurogenic pulmonary edema (NPE) is a life-threatening complication of central nervous system (CNS) injuries. This review summarizes current knowledge about NPE etiology and pathophysiology with an emphasis on its experimental models, including our spinal cord compression model. NPE may develop as a result of activation of specific CNS trigger zones located in the brainstem, leading to a rapid sympathetic discharge, rise in systemic blood pressure, baroreflex-induced bradycardia, and enhanced venous return resulting in pulmonary vascular congestion characterized by interstitial edema, intra-alveolar accumulation of transudate, and intra-alveolar hemorrhages. ⋯ Sympathetic hyperactivity is based on the major activation of either ascending spinal pathways by spinal cord injury or NPE trigger zones by increased intracranial pressure. Attenuation of sympathetic nerve activity or abolition of reflex bradycardia completely prevent NPE development in our experimental model. Suggestions for future research into NPE pathogenesis as well as therapeutic potential of particular drugs and interventions are discussed.
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Journal of neurotrauma · Aug 2015
Clinical TrialEffect of Mild Cold Exposure on Cognition in Persons with Tetraplegia.
Persons with a cervical spinal cord injury (SCI) have impaired thermoregulatory mechanisms secondary to interrupted of motor, sensory, and sympathetic pathways. In this study, our primary aim was to determine the effect of cool temperature exposure on core body temperature (Tcore) and cognitive performance in persons with tetraplegia. Seven men with chronic tetraplegia (C3-C7, American Spinal Injury Association Impairment Scale [AIS] A-C) and seven able-bodied controls were exposed to 27°C temperature at baseline (BL) before being exposed to 18°C for ≤120 min (Cool Challenge). Rectal temperature (Tcore), distal skin temperatures (Tskavg), microvascular skin perfusion (LDFavg), and systolic blood pressure (SBP) were measured. Cognitive performance was assessed using Delayed Recall, Stroop Interference tests at the end of BL and Cool Challenge. After Cool Challenge, Tcore decreased -1.2±0.12°C (p<0.0001) in tetraplegics after an average of 109±15.9 min with no change in controls after 120 min. Tskavg declined in both groups, but decline was less in tetraplegics than in controls (-8.6±5.8% vs. -31.6±7.9%, respectively; p<0.0001). LDFavg declined only in controls (-72±17.9%; p<0.001). Plasma norepinephrine levels differed after Cool Challenge (tetraplegics vs. ⋯ 86±62 pg/mL vs. 832±431 pg/mL, respectively; p<0.01). SBP increased from BL to Cool Challenge only in controls (123±16 mm Hg to 149±17 mm Hg, respectively; p<0.01). Delayed Recall and Stroop Interference scores both declined in tetraplegics (-55±47.4%; p<0.05 and -3.9±3.8%; p<0.05, respectively), but not in controls. We conclude that persons with tetraplegia lack adequate thermoregulatory mechanisms to prevent downward drift in Tcore on exposure to cool temperatures. This decline in Tcore was associated with deterioration of working memory and executive function.
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After spinal cord injury (SCI), a fibrotic scar forms at the injury site that is best characterized by the accumulation of perivascular fibroblasts and deposition of the extracellular matrix protein fibronectin. While fibronectin is a growth-permissive substrate for axons, the fibrotic scar is inhibitory to axon regeneration. The mechanism behind how fibronectin contributes to the inhibitory environment and how the fibronectin matrix is assembled in the fibrotic scar is unknown. ⋯ Assembly of the fibronectin matrix may be mediated by the canonical fibronectin receptor, integrin α5β1, which is primarily expressed by activated macrophages/microglia in the fibrotic scar. Despite the pronounced cavitation after rat SCI, fibrotic scar also is observed in a rat SCI model, which is considered to be more similar to human pathology. Taken together, our study provides insight into the mechanism of fibrotic scar formation after spinal cord injury.