Brain research
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Histone deacetylases (HDAC) inhibitors including valproic acid (VPA) have emerged as a promising therapeutic intervention in neurological disorders. We investigated the levels of acetylated histone and the therapeutic potential of VPA in a rat model of spinal cord injury (SCI). At different time points (12 h, 1 day, 3 days, 1 week and 2 weeks) after SCI or sham surgery, the spinal cords were collected to evaluate the levels of acetylated histone H3 (Ac-H3) and H4 (Ac-H4). ⋯ The levels of Ac-H3 and Ac-H4 in the injured spinal cord started to significantly decrease as early as day 1, and remained below those in uninjured controls for at least 2 weeks after SCI. Injection of VPA markedly prevented the reductions of Ac-H3 and Ac-H4, upregulated the expressions of Hsp70 and Bcl-2, reduced apoptosis and finally promoted locomotion recovery. Our data demonstrated that SCI led to marked reduction in histone acetylation; VPA was neuroprotective in the SCI model, and the mechanism may involve HDAC inhibition and protective proteins induction.
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It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the hind paws of rats. ⋯ In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.
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Recognition and processing of emotional facial expression are crucial for social behavior and employ higher-order cognitive and visual working processes. In neuropsychiatric disorders, impaired emotion recognition most frequently concerned three specific emotions, i.e., anger, fear, and disgust. As incorrect processing of (neutral) facial stimuli per se might also underlie deficits in the recognition of emotional facial expressions, we aimed to assess all these aspects in one experiment. ⋯ Analyzing contrasts between emotional conditions showed similar results (to those of contrasting with reference conditions) for separated emotional network patterns. We demonstrate here that our paradigm reproduces single aspects of separate previous studies across a cohort of healthy subjects, irrespective of age. Our approach might prove useful in future studies of patients with neurologic disorders with potential effect on emotion recognition.
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Previous studies have suggested that substance P (SP) plays a critical role in the development of brain oedema and functional deficits following traumatic brain injury and that SP receptor antagonism may improve outcome. No studies have described such a role in ischemic stroke. The present study characterized the effects of the NK1 tachykinin receptor antagonist, n-acetyl-L-tryptophan (NAT), on blood-brain barrier (BBB) breakdown, oedema formation, infarct volume and functional outcome following reversible ischemic stroke in rats. ⋯ Administration of NAT significantly reduced oedema formation and BBB permeability at 24 h post-ischemia and significantly improved functional outcome as assessed over 7 days. There was no effect on infarct volume. We conclude that inhibition of SP activity with a NK1 tachykinin receptor antagonist is effective in reducing cerebral oedema, BBB permeability and functional deficits following reversible ischemia and may therefore represent a novel therapeutic approach to the treatment of ischaemic stroke.