Brain research
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Traumatic brain injury (TBI) is one of the leading causes of death and disability. Cognitive deficits are believed to be connected with impairments of the cholinergic system. The present study was conducted to evaluate the cholinergic system in a model of focal brain injury with special attention to the time course of posttraumatic events in critical brain regions. ⋯ The same brain regions showed reductions of mAChR at 24 and 72 h after trauma with additional decreases in the corpus callosum, basal forebrain and anterior olfactory nucleus. In conclusion, cholinergic markers showed significant time-dependent impairments after TBI. Considering the role of the cholinergic system for cognitive processes in the brain, it seems likely that these impairments contribute to clinically relevant cognitive deficits.
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Although opioids are known to influence sleep-wake regulation, the neuroanatomic substrate(s) mediating these effects remain unresolved. We hypothesized that the influence of opiates on sleep may be mediated, at least in part, by the ventrolateral preoptic nucleus (VLPO), a key cell group for producing behavioral sleep. By combining in situ hybridization for kappa and mu receptor mRNA with immunostaining of Fos expressed by VLPO cells during sleep we show that >85% of sleep-active VLPO neurons contain mRNA for either or both opioid receptors. ⋯ The sleep- and wake-promoting effects of the kappa and mu agonists were blocked by prior administration of their respective antagonist. Combining retrograde tracing from the VLPO with immunohistochemistry for dynorphin (Dyn, the endogenous kappa receptor agonist) or endomorphin 1 (EM1, the endogenous mu receptor agonist) we show that the central lateral parabrachial subnucleus (PBcl) provides Dyn inputs to the VLPO, whereas hypothalamic histaminergic neurons provide EM1 inputs to the VLPO. In summary, results from the present study suggest that central opioid inputs to the VLPO may play a role in sleep-wake regulation and that the VLPO likely mediates the hypnotic response to high levels of opioid analgesics.
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Peroxisome proliferator-activated receptor (PPAR)-gamma is a ligand-activated transcription factor of nuclear hormone receptor superfamily. Thiazolidinedione rosiglitazone is a potent agonist of PPARgamma which was shown to induce neuroprotection in animal models of focal ischemia and spinal cord injury. We currently evaluated the therapeutic potential of rosiglitazone (6 mg/kg at 5 min, 6 h and 24 h; i.p.) following controlled cortical impact (CCI)-induced traumatic brain injury (TBI) in adult mice. ⋯ In addition, rosiglitazone significantly enhanced the post-TBI expression of the neuroprotective chaperones HSP27, HSP70 and HSP32/HO1, and the anti-oxidant enzymes catalase, Cu/Zn-SOD and Mn-SOD, compared to vehicle. Treatment with GW9662 (a specific PPARgamma antagonist) prevented all the above PPARgamma-mediated actions. Thus, PPARgamma activation confers neuroprotection after TBI by anti-inflammatory, anti-apoptotic and anti-oxidative mechanisms.
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This study was performed to understand the anatomical substrates of hypothalamic modulation of jaw movements. After cholera toxin B subunit (CTb) injection into the parvicellular reticular formation (RFp) of the rat medulla oblongata, where many trigeminal premotor neurons have been known to exist, numerous CTb-labeled neurons were found in the posterior lateral hypothalamus (PLH) bilaterally with a clear-cut ipsilateral dominance. ⋯ It was further revealed that these BDA-labeled axon terminals were immunoreactive for vesicular glutamate transporter 2. The present data suggest that the PLH plays an important role in the control of jaw movements by exerting its glutamatergic excitatory action upon RFp neurons presynaptic to trigeminal motoneurons.
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Eugenol is an aromatic molecule found in several plants and widely used in dentistry for analgesic and antiseptic purposes. It inhibits pro-inflammatory mediators including nitric oxide synthase, cyclooxygenase and lipoxygenase. It also regulates ion channels involved in pain signaling, such as TRPV1 receptor, high-voltage-activated Ca(2+) channels, NMDA receptor and GABA(A) receptor. ⋯ The recovery from inactivation of both Na(+) currents was slowed by eugenol. The eugenol inhibition of Na(+) currents was not dependent on the stimulus frequency. The inhibition of Na(+) currents is considered as one of the mechanisms by which eugenol exerts analgesia.