Journal of neuroscience research
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Exposure to high-pressure blast shock waves is known to cause tinnitus. Although the underlying mechanisms may involve damage to structures in the ear and/or direct brain impact, which triggers a cascade of neuroplastic changes in both auditory and nonauditory centers, it remains unclear how the induced neuroplasticity manifests neurophysiologically. This study investigates the influence of blast exposure on spontaneous firing rates (SFRs) in the dorsal cochlear nucleus (DCN) and its time course in rats with blast-induced tinnitus. ⋯ At 3 months after blast exposure, however, the induced hyperactivity of four rats with tinnitus transitioned to hypoactivity. In addition, the 20-30-kHz, and >30-kHz regions in the DCN of rats with and without blast-induced tinnitus were more affected than other frequency regions at different recovery time points after blast exposure. These results demonstrate that the neural mechanisms underlying blast-induced tinnitus are substantially different from those underlying noise-induced tinnitus.
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Inflammation plays a key role in the development of sensitization after peripheral nerve damage. We recently demonstrated that tumor necrosis factor-α receptor (TNFR) levels in the spinal cord correlate with pain sensation in herniated disc patients in a rat chronic constriction injury (CCI) model. By using the sciatic nerve CCI model, we studied the effect of anti-TNF-α treatment on recovery from hypersensitivity and TNFR expression in the dorsal root ganglion (DRG) and dorsal horn (DH). ⋯ Both treatments significantly diminished these increased levels. Treated animals that showed a ≥50% alleviation of pain exhibited a significantly reduced TNF R1/R2 mRNA ratio compared with treated animals that recovered less well. These results demonstrate that attenuation of TNFR expression is associated with recovery from nerve injury and suggest that this may be one of the working mechanisms of anti-TNF therapies.
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Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet-derived growth factor receptor β-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). ⋯ Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats.
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Although both the onset of schizophrenia and human phencyclidine (PCP) abuse typically present within the interval from adolescence to early adulthood, the majority of preclinical research employing the PCP model of schizophrenia has been conducted on neonatal or adult animals. The present study was designed to evaluate the behavioral and neurochemical sequelae of subchronic exposure to PCP in adolescence. Male 35-42-day-old Sprague Dawley rats were subcutaneously administered either saline (10 ml · kg(-1) ) or PCP hydrochloride (10 mg · kg(-1) ) once daily for a period of 14 days (n = 6/group). ⋯ Spontaneous rearing in response to the novel testing arena and time spent investigating its walls and floor were reduced in PCP-withdrawn animals compared with control. The long-term behavioral effects of PCP occurred in the absence of persistent deficits in spontaneous locomotion or self-grooming activity and were not mediated by altered NMDAR density. Our results document differential effects of adolescent PCP administration on the social and exploratory behaviors of adult rats, suggesting that distinct neurobiological mechanisms are involved in mediating these behaviors.