A-train clusters and the intermedius nerve in vestibular schwannoma patients.

OBJECTIVE: EMG "A-train" activity correlates with postoperative facial palsy after vestibular schwannoma (VS) surgery. An intermedius nerve separate from the facial nerve increases A-trains without significant impact on function. We investigate occurrence of A-train "clusters", A-trains over a majority of channels within a short time frame. METHODS: Data from 217 patients with first surgery for VS were evaluated retrospectively. Continuous EMG recorded with 9 channels was evaluated for A-train patterns. "Clusters" of A-trains were identified, i.e. A-trains within 3 seconds over a majority of channels. Relation to a separate intermedius, tumor size and facial palsy was evaluated. RESULTS: Correlations between A-trains and postoperative facial palsy were higher in patients without separate intermedius (r = 0.562 versus r = 0.194). Clusters were identified in 107 patients (49.3%), separate intermedius in 109 (50.2%), with significant association of both (p < 0.001, Chi-Square test). Excluding clusters slightly increased correlation of A-trains to facial nerve function. CONCLUSIONS: A-train clusters have limited relevance for predicting postoperative paresis. However, they should be regarded as warning signs, suggesting the presence of a separate intermedius nerve. SIGNIFICANCE: A-train "clusters" are a sign of hyperactivity of the facial nerve due to a separate intermedius nerve and may confound intraoperative monitoring during VS surgery.

NF-κB controls axonal regeneration and degeneration through cell-specific balance of RelA and p50 in the adult CNS.

NF-κB is dually involved in neurogenesis and brain pathology. Here, we addressed its role in adult axoneogenesis by generating mutations of RelA (p65) and p50 (also known as NFKB1) heterodimers of canonical NF-κB. In addition to RelA activation in astrocytes, optic nerve axonotmesis caused a hitherto unrecognized induction of RelA in growth-inhibitory oligodendrocytes. Intraretinally, RelA was induced in severed retinal ganglion cells and was also expressed in bystander Müller glia. Cell-type-specific deletion of transactivating RelA in neurons and/or macroglia stimulated axonal regeneration in a distinct and synergistic pattern. By contrast, deletion of the p50 suppressor subunit promoted spontaneous and post-injury Wallerian degeneration. Growth effects mediated by RelA deletion paralleled a downregulation of growth-inhibitory Cdh1 (officially known as FZR1) and upregulation of the endogenous Cdh1 suppressor EMI1 (officially known as FBXO5). Pro-degenerative loss of p50, however, stabilized retinal Cdh1. In vitro, RelA deletion elicited opposing pro-regenerative shifts in active nuclear and inactive cytoplasmic moieties of Cdh1 and Id2. The involvement of NF-κB and cell-cycle regulators such as Cdh1 in regenerative processes of non-replicative neurons suggests novel mechanisms by which molecular reprogramming might be executed to stimulate adult axoneogenesis and treat central nervous system (CNS) axonopathies.

Environmental enrichment extends ocular dominance plasticity into adulthood and protects from stroke-induced impairments of plasticity.

Ocular dominance (OD) plasticity in mouse primary visual cortex (V1) declines during postnatal development and is absent beyond postnatal day 110 if mice are raised in standard cages (SCs). An enriched environment (EE) promotes OD plasticity in adult rats. Here, we explored cellular mechanisms of EE in mouse V1 and the therapeutic potential of EE to prevent impairments of plasticity after a cortical stroke. Using in vivo optical imaging, we observed that monocular deprivation in adult EE mice (i) caused a very strong OD plasticity previously only observed in 4-wk-old animals, (ii) restored already lost OD plasticity in adult SC-raised mice, and (iii) preserved OD plasticity after a stroke in the primary somatosensory cortex. Using patch-clamp electrophysiology in vitro, we also show that (iv) local inhibition was significantly reduced in V1 slices of adult EE mice and (v) the GABA/AMPA ratio was like that in 4-wk-old SC-raised animals. These observations were corroborated by in vivo analyses showing that diazepam treatment significantly reduced the OD shift of EE mice after monocular deprivation. Taken together, EE extended the sensitive phase for OD plasticity into late adulthood, rejuvenated V1 after 4 mo of SC-rearing, and protected adult mice from stroke-induced impairments of cortical plasticity. The EE effect was mediated most likely by preserving low juvenile levels of inhibition into adulthood, which potentially promoted adaptive changes in cortical circuits.

Simvastatin improves retinal ganglion cell survival and spatial vision after acute retinal ischemia/reperfusion in mice.

PURPOSE: The major aims of this study were to evaluate the effect of retinal ischemia by behavioral testing and histologic analyses, to visualize ischemia-induced changes of cortical activity by optical imaging of intrinsic signals, and to test the therapeutic effectiveness of simvastatin. METHODS: Retinal ischemia was induced monocularly by elevating intraocular pressure. Visual function was tested behaviorally with a virtual reality optomotor system, physiologically with optical imaging of intrinsic signals, and histologically by counting the surviving retinal ganglion cells (RGCs) in the same animal. RESULTS: Visual acuity (-38%) and contrast sensitivity (-78%) were significantly reduced 6 days after ischemia compared with controls. The number of RGCs was reduced by 16%. In contrast, optical imaging revealed essentially unchanged cortical activity maps in spite of the lesion. Treatment of mice with simvastatin applied after the ischemic insult significantly improved both visual function as measured behaviorally (~95% visual acuity, ~165% contrast sensitivity) and RGC survival (~30%) compared with vehicle-treated animals (~42% visual acuity, ~85% contrast sensitivity). CONCLUSIONS: This specific combination of behavioral measurements of visual function, cortical activity imaging, and histologic analyses is ideally suited to follow ischemia-induced changes and to monitor the effect of therapeutic approaches. Statin therapy may be a promising pharmacologic tool for the treatment of acute retinal ischemia in particular because, in our study, simvastatin was applied after ischemia, a treatment regimen with much greater clinical relevance than preventive administration, as in previous studies.