The Journal of neuroscience : the official journal of the Society for Neuroscience
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Autonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immune suppression are not known. ⋯ Reversal of postinjury immune suppression in SCI mice can be achieved by pharmacological inhibition of receptors for norepinephrine and glucocorticoids during the onset and progression of AD. In a human subject with C5 SCI, stimulating the micturition reflex caused AD with exaggerated catecholamine release and impaired immune function, thus confirming the relevance of the mouse data. These data implicate AD as a cause of secondary immune deficiency after SCI and reveal novel therapeutic targets for overcoming infectious complications that arise due to deficits in immune function.
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It remains unclear to what extent retinotopic maps can undergo large-scale plasticity following damage to human visual cortex. The literature has predominately focused on retinotopic changes in patients with retinal pathologies or congenital brain malformations. Yet, damage to the adult visual cortex itself is common in cases such as stroke, tumor, or trauma. ⋯ Both adult-onset cases had direct damage to early visual cortex itself (rather than to the afferent drive only), resulting in a mostly nonfunctional hemisphere. The congenital case had severe cortical malformation of the visual cortex and was acallosal. Our results are consistent with a competitive model in which unilateral damage to visual cortex or disruption of the transcallosal connections removes interhemispheric suppression from retino-geniculate afferents in intact visual cortex that represent the vertical meridian and ipsilateral visual field.
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Spinal cord injury results in distant pathology around putative locomotor networks that may jeopardize the recovery of locomotion. We previously showed that activated microglia and increased cytokine expression extend at least 10 segments below the injury to influence sensory function. Matrix metalloproteinase-9 (MMP-9) is a potent regulator of acute neuroinflammation. ⋯ Neither training nor MMP-9 depletion alone promoted recovery. The same intervention delivered late was ineffective, suggesting that lesion site sparing is insufficient to facilitate activity-based training and recovery. Our work suggests that by attenuating remote mechanisms of inflammation, acute treadmill training can harness endogenous spinal plasticity to promote robust recovery.
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The perirhinal cortex (PRh) and basolateral amygdala (BLA) appear to mediate distinct aspects of learning and memory. Here, we used rats to investigate the involvement of the PRh and BLA in acquisition and extinction of associations between two different environmental stimuli (e.g., a tone and a light) in higher-order conditioning. When both stimuli were neutral, infusion of the GABAA, muscimol, or the NMDA receptor (NMDAR) antagonist ifenprodil into the PRh impaired associative formation. ⋯ When training was conducted in a dangerous environment, formation and extinction of an association between neutral stimuli was impaired by BLA inactivation or NMDAR blockade in this region, but was unaffected by PRh inactivation. These double dissociations in the roles of the PRh and BLA in learning under different stimulus and environmental conditions imply that fear-induced activation of the amygdala changes how the brain processes sensory stimuli. Harmless stimuli are treated as potentially harmful, resulting in a shift from cortical to subcortical processing in the BLA.