Experimental neurology
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Experimental neurology · Dec 2012
Chronic noise exposure causes persistence of tau hyperphosphorylation and formation of NFT tau in the rat hippocampus and prefrontal cortex.
The non-auditory effects of noise exposure on the central nervous system have been established both epidemiologically and experimentally. Chronic noise exposure (CNE) has been associated with tau hyperphosphorylation and Alzheimer's disease (AD)-like pathological changes. However, experimental evidence for these associations remains limited. ⋯ Furthermore, lasting increases in proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A), were found to occur in close correspondence with increase in tau hyperphosphorylation. The results of this study show that CNE leads to long-lasting increases in non-NFT hyperphosphorylated tau and delayed formation of misfolded NFT tau in the hippocampus and the prefrontal cortex. Our results also provide evidence for the involvement of GSK3β and PP2A in these processes.
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Experimental neurology · Oct 2012
Neuroprotective effects of the sigma-1 receptor ligand PRE-084 against excitotoxic perinatal brain injury in newborn mice.
Excessive glutamate release followed by N-methyl-D-aspartate receptor (NMDAR) activation plays a crucial role in perinatal brain injury. We have previously shown that dextromethorphan, a low-affinity NMDAR antagonist with anti-inflammatory properties, is neuroprotective against neonatal excitotoxic brain injury. Of interest, dextromethorphan is also a sigma-1 receptor (σ1R) agonist. ⋯ PRE-084 had no effect on developmental apoptosis in the undamaged brain. In vitro findings in primary hippocampal neurons suggest that PRE-084 treatment provides partial protection against glutamate induced morphological and functional changes. For excitotoxicity as playing a crucial role in the pathogenesis of perinatal brain injury, we demonstrate for the first time that systemic treatment with the highly selective σ1R agonist PRE-084 protects against NMDAR-mediated excitotoxic brain damage.
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Severed axons in adult mammals do not regenerate appreciably after central nervous system (CNS) injury due to developmentally determined reductions in neuron-intrinsic growth capacity and extracellular environment for axon elongation. Chondroitin sulfate proteoglycans (CSPGs), which are generated by reactive scar tissues, are particularly potent contributors to the growth-limiting environment in mature CNS. Thus, surmounting the strong inhibition by CSPG-rich scar is an important therapeutic goal for achieving functional recovery after CNS injuries. ⋯ CSPGs also may act by binding to two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3 (NgR1 and NgR3). If confirmed, it would suggest that CSPGs have multiple mechanisms by which they inhibit axon growth, making them especially potent and difficult therapeutic targets. Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries, including spinal cord injury (SCI).
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Experimental neurology · Oct 2012
Subthalamic local field potentials after seven-year deep brain stimulation in Parkinson's disease.
Studies describing subthalamic (STN) local field potentials (LFPs) recorded during deep brain stimulation (DBS) in patients with Parkinson's disease (PD), within the first month after DBS electrode implant, show that DBS modulates specific STN oscillations: whereas low-frequency (LF) oscillations (2-7 Hz) increase, beta oscillations (8-30 Hz) variably decrease. No data show whether LFPs remain stable for longer than one month after DBS surgery. Having long-term information is essential especially for use as a long-term feedback control signal for adaptive DBS systems. ⋯ STN recordings showed similar LFP responses to DBS in the acute and hyperchronic stages: whereas during ongoing DBS the LF power band increased for the whole population, beta activity decreased only in nuclei with significant beta activity at baseline. The LF/beta power ratio in all nuclei changed in both study groups, suggesting that this variable might be an even more informative marker of PD than the single LF and beta bands. Because STN LFP activity patterns and STN LFP responses to DBS stay almost unchanged for years after DBS electrode implantation they should provide a consistent feedback control signal for adaptive DBS.
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Experimental neurology · Oct 2012
Cerebralcare Granule® attenuates blood-brain barrier disruption after middle cerebral artery occlusion in rats.
Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, for which the current clinical therapy remains unsatisfied. Cerebralcare Granule® (CG) is a compound Chinese medicine widely used in China for treatment of cerebrovascular diseases. CG has been demonstrated efficacy in attenuating the cerebral microcirculatory disturbance and hippocampal neuron injury following global cerebral ischemia. ⋯ Western blot analysis and confocal microscopy showed that the tight junction proteins claudin-5, JAM-1, occludin and zonula occluden-1 between endothelial cells were significantly degradated, but the protein expression of caveolin-1, the principal marker of caveolae in endothelial cells, increased after ischemia, all of which were alleviated by CG treatment. In conclusion, the post-treatment with CG significantly reduced BBB permeability and brain edema, which were correlated with preventing the degradation of the tight junction proteins and inhibiting the expression of caveolin-1 in the endothelial cells. These findings provide a novel approach to the treatment of ischemic stroke.