Brain research
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Previously, we identified 14-3-3 beta and zeta isoforms and proteolytic fragments of alpha-spectrin as proteins released from degenerating neurons that also rise markedly in cerebrospinal fluid (CSF) following experimental brain injury or ischemia in rodents, but these proteins have not been studied before as potential biomarkers for ischemic central nervous system injury in humans. Here we describe longitudinal analysis of these proteins along with the neuron-enriched hypophosphorylated neurofilament H (pNFH) and the deubiquitinating enzyme UCH-L1 in lumbar CSF samples from 19 surgical cases of aortic aneurysm repair, 7 involving cardiopulmonary bypass with deep hypothermic circulatory arrest (DHCA). CSF levels of the proteins were near the lower limit of detection by Western blot or enzyme-linked fluorescence immunoassay at the onset of surgical procedures, but increased substantially in a subset of cases, typically within 12-24 h. ⋯ Six of 7 also exhibited marked increases in alpha-spectrin fragments generated by calpain, a protease known to trigger necrotic neurodegeneration. Among cases involving aortic cross-clamping but not DHCA, the proteins rose in CSF preferentially in the subset experiencing acute neurological complications. Our results suggest the neuron-enriched 14-3-3beta, 14-3-3zeta, pNFH, UCH-L1, and calpain-cleaved alpha-spectrin may serve as a panel of biomarkers with clinical potential for the detection and management of ischemic central nervous system injury, including for mild damage associated with surgically-induced circulation arrest.
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Memory impairment is common following traumatic brain injury. However, the specific processes underlying the impairments remain unknown. Traumatic brain injury may interfere with several of the stages of the learning and memory process. ⋯ However, after the reminding procedure, injured animals displayed sham-level performance during the second probe trial. The results of these experiments suggest that with anterograde memory impairment induced by traumatic brain injury, the primary deficit lies in task acquisition, not the retention of information within long-term memory. Retrograde memory impairment following injury appears to be mediated primarily by deficits in memory retrieval.
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The magnocellular reticular nucleus and adjacent lateral paragigantocellular nucleus have been shown to contain a large population of nitric oxide synthase (NOS) immunoreactive neurons. However, little is known about the projections of these neurons within the central nervous system. Retrograde tract-tracing techniques combined with immunohistochemistry were used in this study to investigate whether NOS neurons in this rostral ventromedial medullary (RVMM) region send collateral axonal projections to autonomic sites in the nucleus of the solitary tract (NTS) and in the nucleus ambiguus (Amb). ⋯ Of these double labeled neurons, 36.4+/-20 (39%) were also found to be immunoreactive to NOS. These data indicate that the RVMM contains at least three population of NOS neurons that send axons to innervate functionally similar cardiovascular responsive sites in the NTS and Amb. Although the function of these NOS containing medullary pathways in cardiovascular control is not known, it is likely that those with collateral axonal projections represent the anatomical substrate by which the RVMM may simultaneously coordinate cardiovascular responses during physiological changes associated with respiration and/or motor movements.
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Glutamate-induced excitotoxicity is considered as a major cause of neurodegenerative disease. Excitatory amino acid transporters (EAATs) on glial cells are responsible for the homeostasis of extracellular glutamate in the central nervous system which may contribute to the prevention of excitotoxic neurodegeneration. However, the differential EAAT expression in astrocytes and microglia is not fully understood. ⋯ Astrocytes rescued neurons from microglial glutamate-induced death in a ratio-dependent manner. Inhibition of EAATs abolished glutamate uptake and the neuroprotective effect of astrocytes, but it did not alter any microglial neurotoxic or neuroprotective effects. These results revealed that astrocytic EAATs can counteract microglial glutamate-induced neuronal death whereas microglial EAATs are inconsequential to neurotoxicity and neuroprotection.
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The analgesic effects of tramadol are considered to be mediated by both the opioid system and the serotonergic system. This study investigated the involvement of a subtype of serotonin receptors, 5-hydroxytryptamine (5-HT)2A receptor, in the analgesic effect of tramadol. The intraperitoneal (i.p.) injection of tramadol reduced the paw withdrawal latency (PWL) to radiant heat testing in mono-arthritic rats. ⋯ These results suggest that 5-HT2A receptors are involved in the analgesic effect of tramadol. This study provides evidence for involvement of 5-HT2A receptors in the tramadol analgesia of inflammatory pain. The increase in this receptor mRNA in the chronic study may contribute to the sustaining effect of tramadol long-term treatments in clinical practice.