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Brain Trauma (brain + trauma)
Selected AbstractsA role for the volume regulated anion channel in volume regulation in the murine CNS cell line, CADACTA PHYSIOLOGICA, Issue 2 2010V. L. Harvey Abstract Aim:, The role of the volume regulated anion channel (VRAC) in a model CNS neuronal cell line, CAD, was investigated. Methods:, Changes in cell volume following hypotonic challenges were measured using a video-imaging technique. The effect of the Cl, channel antagonists tamoxifen (10 ,m) and 4,4,-diisothiocyanatostilbene-2,2,-disulphonic acid (DIDS; 100 ,m) on regulatory volume decrease (RVD) were measured. The whole-cell voltage-clamp technique was used to characterize IClswell, the current underlying the VRAC. Results:, Using the video-imaging technique, CAD cells were found to swell and subsequently exhibit RVD when subjected to a sustained hypotonic challenge from 300 mOsmol kg,1 H2O to 210 mOsmol kg,1 H2O. In the presence of tamoxifen (10 ,m) or DIDS (100 ,m) RVD was abolished, suggesting a role for the VRAC. A hypotonic solution (230 mOsmol kg,1 H2O) evoked IClswell, an outwardly rectifying current displaying time-independent activation, which reversed upon return to isotonic conditions. The reversal potential (Erev) for IClswell was ,14.7 ± 1.4 mV, similar to the theoretical Erev for a selective Cl, conductance. IClswell was inhibited in the presence of DIDS (100 ,m) and tamoxifen (10 ,m), the DIDS inhibition being voltage dependent. Conclusions:, Osmotic swelling elicits an outwardly rectifying Cl, conductance in CAD cells. The IClswell observed in these cells is similar to that observed in other cells, and is likely to provide a pathway for the loss of Cl, which leads to water loss and RVD. As ischaemia, brain trauma, hypoxia and other brain pathologies can cause cell swelling, CAD cells represent a model cell line for the study of neuronal cell volume regulation. [source] Characterization of mouse marrow stromal cellsJOURNAL OF NEUROCHEMISTRY, Issue 2002S. S Liour Neural transplantation is a promising therapy for neurodegenerative diseases, including Parkinson's, Huntington's, Alzeheimer's, as well as mucopolysaccharidoses. However, neural transplantation is an invasive procedure in the early stages of research and development. In contrast, bone marrow transplantation has been used in medical treatment of immune and hematological disorders and genetic diseases. A increasing number of research reports suggest that cells derived from bone marrow, particularly mesenchymal stem cells, cannot only migrate into brains of recipient rodents after IV administration, but also differentiate into neurons and glia, to facilitate the functional recovery of rats after stroke or brain trauma. The lack of exclusive cell markers for mesenchymal stem cells makes them difficult to study. We isolated mouse marrow stromal cells and studied the expression of markers, particularly glycosphingolipids on their cell surface. Bone marrow was aspirated from femurs of two-month-old mice, and the stromal cells were propagated in attached cultures. Immuncytochemical analysis suggested that most stromal cells were immunopositive for antibodies against IGFR, flk-1, and CD44. Analysis of the glycosphingolipid composition by HPTLC revealed that GM3, GM2, GM1, and GD1a were the major gangliosides expressed in stromal cell in culture. Glucosylceramide, lactosylceramide, and paragloboside were the major neutral glycolipids expressed in these cells. Combinations of these cell surface markers may prove useful in the isolation and characterization of mesenchymal stem cells. Acknowledgements:, Supported by grants from NIH NS11853 and the Children's Medical Research Foundation. [source] Diffusion Tensor and Functional Magnetic Resonance Imaging of Diffuse Axonal Injury and Resulting Language ImpairmentJOURNAL OF NEUROIMAGING, Issue 4 2007Hui Mao PhD ABSTRACT Diffuse axonal injury (DAI) is a common aftermath of brain trauma. The diagnosis of DAI is often difficult using conventional magnetic resonance imaging (MRI). We report a diffusion tensor imaging (DTI) study of a patient who sustained DAI presenting with language impairment. Fractional anisotropy (FA) and DTI tractography revealed a reduction of white matter integrity in the left frontal and medial temporal areas. White matter damage identified by DTI was correlated with the patient's language impairment as assessed by functional MRI (fMRI) and a neuropsychological exam. The findings demonstrate the utility of DTI for identifying white matter changes secondary to traumatic brain injury (TBI). [source] Apoptotic and behavioral sequelae of mild brain trauma in miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2007David Tweedie Abstract Mild traumatic brain injury (mTBI) is a not uncommon event in adolescents and young adults. Although it does not result in clear morphological brain defects, it is associated with long-term cognitive, emotional, and behavioral problems. Herein, we characterized the biochemical and behavioral changes associated with experimental mTBI in mice that may act as either targets or surrogate markers for interventional therapy. Specifically, mTBI was induced by 30-g and 50-g weight drop, and at 8 and 72 hr thereafter markers of cellular apoptosis,caspase-3, Bax, apoptosis-inducing factor (AIF), and cytochrome-c (Cyt-c),were quantified by Western blot analysis in hippocampus ipsilateral to the impact. Levels of amyloid-, precursor protein (APP) were also measured, and specific behavioral tests,passive avoidance, open field, and forced swimming (Porsolt) paradigms,were undertaken to assess learning, emotionality, and emotional memory. In the absence of hemorrhage or infarcts, as assessed by triphenyltetrazolium chloride staining, procaspase-3 and Bax levels were markedly altered following mTBI at both times. No cleaved caspase-3 was detected, and levels of AIF and Cyt-c, but not APP, were significantly changed at 72 hr. Mice subjected to mTBI were indistinguishable from controls by neurological examination at 1 and 24 hr, and by passive avoidance/open field at 72 hr, but could be differentiated in the forced swimming paradigm. In general, this model mimics the diffuse effects of mTBI on brain function associated with the human condition and highlights specific apoptotic proteins and a behavioral paradigm as potential markers for prospective interventional strategies. © 2007 Wiley-Liss, Inc. [source] Expression patterns of 5-lipoxygenase in human brain with traumatic injury and astrocytomaNEUROPATHOLOGY, Issue 2 2006Lei Zhang 5-Lipoxygenase (5-LOX) is a key enzyme in the metabolism of arachidonic acid to leukotrienes. The levels of leukotrienes increase after brain injury and when tumors are present. It has been reported that 5-LOX is widely expressed in the brain and that 5-LOX inhibition provides neuroprotection. However, there is still no information available for the expression patterns of 5-LOX in human brain following trauma or with astrocytomas. We investigated its expression patterns by immunohistochemistry. We found that 5-LOX is normally expressed in neurons and glial cells. In neurons, it was expressed in two patterns: in the cytosol and nucleus or only in the cytosol. In traumatic brain injury, 5-LOX expression increased in glial cells and neutrophils. Double-labeling immunohistochemistry showed that part of the 5-LOX-positive glial cells were GFAP positive. No 5-LOX expression was found in brain microvessel endothelia, except in the regenerated endothelia of a patient 8 days following brain trauma. Furthermore, 5-LOX expression increased and showed a granular pattern in high-grade (grade III/IV) astrocytoma. These results indicate that 5-LOX has multiple expression patterns, and can be induced by brain injury, which implies that 5-LOX might have pathophysiological roles in the human brain. [source] Low-dose prostacyclin in treatment of severe brain trauma evaluated with microdialysis and jugular bulb oxygen measurementsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2000P.-O. Grände Background: The endogenous substance prostacyclin is a substance with the potential to improve microcirculation and oxygenation around contusions in the brain following a head trauma by its vasodilatory, antiaggregatory and antiadhesive effects. Microdialysis measurements of local concentrations of selected interstitial substances in the brain, and measurements of venous jugular bulb oxygenation reflecting overall brain oxygenation, might be useful to evaluate possible therapeutic effects of a specific therapy, such as treatment with prostacyclin. Methods: This case report study on six patients, of whom five were given prostacyclin, includes cerebral microdialysis measurements of interstitial lactate (n=5), pyruvate (n=3), glycerol (n=5) and glucose (n=4), and is combined with measurements of venous jugular bulb oxygenation in three of the patients. One microdialysis catheter was placed adjacent to a contusion, and in four of the patients another catheter was also placed in the contralateral less injured side for comparison. Low-dose prostacyclin infusion (0.5,1.0 ng kg,1 min,1) was started when lactate concentrations in the more injured side was raised at a constant level for more than 10 h. The study also includes one patient used as control to whom no prostacyclin was given. Results: Lactate was markedly lower in the less injured than in the more injured area of the brain. During the prostacyclin infusion elevated lactate and lactate/pyruvate ratio were reduced. Elevated glycerol decreased, a low glucose increased and jugular bulb blood oxygenation increased following start of prostacyclin. The control patient showed an increase in lactate and lactate/pyruvate ratio. Conclusion: The microdialysis data combined with the jugular bulb oxygenation data indicated that low-dose prostacyclin exerts effects compatible with improved oxygenation and reduced cell damage in the severely traumatised brain. [source] Stimulating neuroregeneration as a therapeutic drug approach for traumatic brain injuryBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2009Bernhard K Mueller Traumatic brain injury, a silent epidemic of modern societies, is a largely neglected area in drug development and no drug is currently available for the treatment of patients suffering from brain trauma. Despite this grim situation, much progress has been made over the last two decades in closely related medical indications, such as spinal cord injury, giving rise to a more optimistic approach to drug development in brain trauma. Fundamental insights have been gained with animal models of central nervous system (CNS) trauma and spinal cord injury. Neuroregenerative drug candidates have been identified and two of these have progressed to clinical development for spinal cord injury patients. If successful, these drug candidates may be used to treat brain trauma patients. Significant progress has also been made in understanding the fundamental molecular mechanism underlying irreversible axonal growth arrest in the injured CNS of higher mammals. From these studies, we have learned that the axonal retraction bulb, previously regarded as a marker for failure of regenerative growth, is not static but dynamic and, therefore, amenable to pharmacotherapeutic approaches. With the development of modified magnetic resonance imaging methods, fibre tracts can be visualised in the living human brain and such imaging methods will soon be used to evaluate the neuroregenerative potential of drug candidates. These significant advances are expected to fundamentally change the often hopeless situation of brain trauma patients and will be the first step towards overcoming the silent epidemic of brain injury. [source] | |||||||||||||