Neuroscience
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Neuroinflammation plays an important role in nerve-injury-induced neuropathic pain, but the explicit molecular mechanisms of neuroinflammation in neuropathic pain remain unclear. As one of the most critical inflammatory cytokines, interleukin-1β (IL-1β) has been regarded as broadly involved in the pathology of neuropathic pain. The inflammasome caspase-1 platform is one primary mechanism responsible for the maturation of IL-1β. ⋯ After rats were subjected to the CCI surgery, mature IL-1β was significantly increased in the ipsilateral spinal cord, and the inflammasome platform consisting of NALP1 (NAcht leucine-rich-repeat protein 1), caspase-1 and ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain) was also activated in spinal astrocytes and neurons, especially at the superficial laminae of the spinal dorsal horn; The aspirin-triggered-15-epi-lipoxin A4 (ATL), which shares the potent actions of the endogenous lipoxins, was administered to the CCI rats. Repeated intrathecal injection with ATL markedly attenuated the CCI-induced thermal hyperalgesia and significantly inhibited NALP1 inflammasome activation, caspase-1 cleavage, and IL-1β maturation. These results suggested that spinal NALP1 inflammasome was involved in the CCI-induced neuropathic pain and that the analgesic effect of ATL was associated with suppressing NALP1 inflammasome activation.
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Sex differences in the visual system have been reported in aspects of human vision, such as color perception, peripheral vision and even in the activation of the primary visual cortex. Similarly sex differences have been identified in the visual system of laboratory animals such as monkeys and rats. On the other hand, environmental enrichment (EE) has long been known to affect visual tissues. ⋯ Late enrichment increased the serotonergic activity in the retina and visual cortex of both sexes (P90-P150), but increased the dopaminergic activity in the visual cortex only in male animals. In the present study we expose marked sex differences in the neurochemistry of visual tissues and we demonstrate for the first time that EE can in fact modify the serotonergic and dopaminergic neurotransmission in the retina and visual cortex. Overall, the present study underpins the sex-dependent neurochemical status of the visual system and provides insights into the different mechanisms underlying visual processing in the two sexes.
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Exposure of mice to a brief light stimulus during their nocturnal active phase induces several simultaneous behavioral or physiological responses, including circadian rhythm phase shifts, a drop in core body temperature (Tc), suppression of locomotor activity and sleep. Each response is triggered by light, endures for a relatively fixed interval and does not require additional light for expression. The present studies address the ability of the psychostimulant drugs, methamphetamine (MA), modafinil (MOD) or caffeine (CAF), to modify the light-induced responses. ⋯ CAF acutely elevated Tc; MA acutely lowered it, but both drugs reduced Tc during the early dark (ZT12.5-ZT13). The ability of the psychostimulant drugs to block the several effects of light exposure is not the result of drug-induced hyperactivity. The results raise questions concerning the manner in which drugs, activity, sleep and Tc influence behavioral and physiological responses to light.
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Using structural magnetic resonance imaging in a clinical scanner at 3.0T, we describe results showing that following 12weeks on a diet of 2% cholesterol, rabbits experience a significant increase in the volume of the third ventricle compared to rabbits on a diet of 0% cholesterol. Using time-of-flight magnetic resonance angiography, we find cholesterol-fed rabbits also experience a decrease in the diameter of a number of cerebral blood vessels including the basilar, posterior communicating, and internal carotid arteries. Taken together, these data confirm that, despite the inability of dietary cholesterol to cross the blood-brain barrier, it does significantly enlarge ventricular volume and decrease cerebrovascular diameter in the rabbit - effects that are also seen in patients with Alzheimer's disease.
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The purpose of this study was to examine the dose-response effectiveness of d-methionine (d-met) in rescuing a noise-induced permanent threshold shift (PTS) and cochlear biochemistry following noise exposure. One hour after being exposed to continuous broadband white noise at 105dB sound pressure level (SPL) for 6h, guinea-pigs were treated five times at 12-h intervals with 200, 400, or 600mg/kg d-met or sterile 0.9% saline (each group, N=6) by intraperitoneal injection. Six guinea-pigs with normal hearing that were not exposed to noise served as control animals. ⋯ The attenuation of the noise-induced decreases in the activities of the Na(+), K(+)-ATPase and Ca(2+)-ATPase following treatment with 200, 400, or 600mg/kg d-met was also dose dependent. Likewise, d-met-dose-dependent decreases in mean lipid peroxidation and nitric oxide levels were observed in the d-met treated groups. Significant attenuation of increased oxidative stress and decreased ATPase activities was concurrent with the d-met-mediated improvements in noise-induced auditory dysfunction.