Experimental neurology
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Experimental neurology · Jan 2012
System x(c)(-) regulates microglia and macrophage glutamate excitotoxicity in vivo.
It is widely believed that microglia and monocyte-derived macrophages (collectively referred to as central nervous system (CNS) macrophages) cause excitotoxicity in the diseased or injured CNS. This view has evolved mostly from in vitro studies showing that neurotoxic concentrations of glutamate are released from CNS macrophages stimulated with lipopolysaccharide (LPS), a potent inflammogen. We hypothesized that excitotoxic killing by CNS macrophages is more rigorously controlled in vivo, requiring both the activation of the glutamate/cystine antiporter (system x(c)(-)) and an increase in extracellular cystine, the substrate that drives glutamate release. ⋯ Surprisingly, neither LPS nor LPS+cystine adversely affects survival of oligodendrocytes or oligodendrocyte progenitor cells. Ex vivo analyses show that redox balance in microglia and macrophages is controlled by induction of system x(c)(-) and that high GSH:GSSG ratios predict the neurotoxic potential of these cells. Together, these data indicate that modulation of redox balance in CNS macrophages, perhaps through regulating system x(c)(-), could be a novel approach for attenuating injurious neuroinflammatory cascades.
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Experimental neurology · Jan 2012
Cerebral blood flow during reperfusion predicts later brain damage in a mouse and a rat model of neonatal hypoxic-ischemic encephalopathy.
Children with severe neonatal hypoxic-ischemic encephalopathy (HIE) die or develop life-long neurological impairments such as cerebral palsy and mental retardation. Decreased regional cerebral blood flow (CBF) is believed to be the predominant factor that determines the level of tissue injury in the immature brain. However, the spatio-temporal profiles of CBF after neonatal HIE are not well understood. ⋯ A similar trend in results was found in rats. These results suggest that the CBF level during reperfusion may be a useful predictive factor for later brain damage in immature mice. This may enable optimizing brain damage for detail analyses.
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In this review, we focus on the relationship among Parkinson's disease (PD), stress and depression. Parkinson's disease patients have a high risk of developing depression, and it is possible that stress contributes to the development of both pathologies. ⋯ However, relatively few studies have examined stress or depression and the injured nigrostriatal system. This review discusses the effects of stress on neurodegeneration and depression, and their association with the symptoms and progression of PD.
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Experimental neurology · Jan 2012
ReviewStress and visceral pain: from animal models to clinical therapies.
Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. ⋯ Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain.
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Experimental neurology · Jan 2012
Clinical TrialThe role of the sub-thalamic nucleus in the preparation of volitional movement termination in Parkinson's disease.
The sub-thalamic nucleus (STN) is relevant to the preparation of movement ignition but its role in movement termination is uncertain. Fourteen patients with Parkinson's disease (PD) received local field potentials (LFPs) recording at the left STN on the fourth day after deep brain stimulation surgery. They performed phasic and tonic movements of the right wrist extensor. ⋯ Alpha, low-beta, and high-beta ERD all appeared about 1s prior to the Moff tonic movement. The current findings suggest that STN participates in the preparation of volitional movement termination but via a different mechanism from that in movement initiation. Unlike asynchronous ERD frequency bands present in movement initiation, a simultaneous ERD across wide frequency bands in STN may play a pivotal role in terminating volitional movement.