Pulsed radiofrequency (PRF) is a percutaneous, micro-invasive, and micro-destructive neuromodulation technology. It has been reported to be useful in the treatment of supraorbital neuralgia (SN). However, the long-term effectiveness and safety of this technique in SN has not been reported yet.To investigate the outcomes of PRF on supraorbital neuralgia (SN) in multi-centers and a long-term perspective.Retrospective case series.Patients who underwent PRF for SN at 4 hospitals in Beijing between Jan 2007 and Jan 2021 were identified and reviewed for inclusion. Their demographic data and baseline conditions were statistically described, and their conditions of pain control were analyzed using Kaplan-Meier survival analyses. A survival curve was plotted, the cumulative proportion of pain-free at specific time points was determined, and the median pain-free time was estimated. Complications related to PRF treatment were summarized. The risk factors for initial pain control and pain-free survival were analyzed using logistic regression and Cox regression.A total of 116 patients were included; 91 (78.4%) patients got initial pain control with just one attempt of PRF. The maximum length of follow-up was 127 months, with a median of 18 months. During follow-up, 29 (31.9%) patients suffered from pain recurrence, and 11 (12.1%) were lost. The cumulative pain-free survival at 6 months, 1 year, 2 years, 3 years, 5 years, 8 years, and 10 years were estimated as 70%, 64%, 59%, 55%, 44%, 37%, and 37%, respectively. The median pain-free time was 52 months. No severe complications were observed or reported. Duration of disease could significantly influence initial pain control, while no risk factors for pain-free survival were recognized.A retrospective study setting without a control group.The performance of PRF for the treatment of SN was confirmed to be favorable in a multicentric, relatively large scale, and long-term perspective.
Abstract Astrocytes and microglia undergo dynamic and complex morphological and functional changes following ischemic stroke, which are instrumental in both inflammatory responses and neural repair. While gene expression alterations poststroke have been extensively studied, investigations into posttranscriptional regulatory mechanisms, specifically alternative splicing (AS), remain limited. Utilizing previously reported Ribo‐Tag‐seq data, this study analyzed AS alterations in poststroke astrocytes and microglia from young adult male and female mice. Our findings reveal that in astrocytes, compared to the sham group, 109 differential alternative splicing (DAS) events were observed at 4 h poststroke, which increased to 320 at day 3. In microglia, these numbers were 316 and 266, respectively. Interestingly, the disparity between DAS genes and differentially expressed genes is substantial, with fewer than 10 genes shared at both poststroke time points in astrocytes and microglia. Gene ontology enrichment analysis revealed the involvement of these DAS genes in diverse functions, encompassing immune response ( Adam8 , Ccr1 ), metabolism ( Acsl6 , Pcyt2, Myo5a ), and developmental cell growth ( App ), among others. Selective DAS events were further validated by semiquantitative RT‐PCR. Overall, this study comprehensively describes the AS alterations in astrocytes and microglia during the hyperacute and acute phases of ischemic stroke and underscores the significance of certain hub DAS events in neuroinflammatory processes.
Abstract The structure of the human neocortex underlies species-specific features and is a reflection of intricate developmental programs. Here we analyzed neocortical cellular lineages through a comprehensive assessment of brain somatic mosaicism—which acts as a neutral recorder of lineage history. We employed deep whole genome and variant sequencing in a single postmortem neurotypical human brain across 25 anatomic regions and three distinct modalities: bulk geographies, sorted cell types, and single nuclei. We identified 259 mosaic variants, revealing remarkable differences in localization, clonal abundance, cell type specificity, and clade distribution. We identified a set of hierarchical cellular diffusion barriers, whereby the left-right axis separation of the neocortex occurs prior to anterior-posterior and dorsal-ventral axis separation. We also found that stochastic distribution is a driver of clonal dispersion, and that rules regarding cellular lineages and anatomical boundaries are often ignored. Our data provides a comprehensive analysis of brain somatic mosaicism across the human cerebral cortex, deconvolving clonal distributions and migration patterns in the human embryo. One Sentence Summary Comprehensive evaluation of brain somatic mosaicism in the adult human identifies rules governing cellular distribution during embryogenesis.
The assembly of neuronal circuits depends on the correct wiring of axons and dendrites. Studies in our laboratory revealed a critical role of seven-pass atypical cadherin Celsr3, a member of planar cell polarity (PCP) proteins, in the development of axonal tracts in the central nervous system, such as the anterior commissure, internal capsule and corticospinal tract. Celsr3 deficiency does not alter axonal growth, but affects axon guidance in cell-autonomous or non-cell-autonomous manners, causing axon stalling at intermediate targets or rerouting. Notably, all axon guidance defects in Celsr3−/− were observed in mice bearing mutations in the PCP gene Fzd3, and some errors were reported in mice with mutations of Vangl2, another PCP gene. Despite their unequivocally role, underlying molecular mechanisms remain elusive. Furthermore, their functions in the peripheral nervous system are still largely unexplored. Here we show that Celsr3 cooperates with Fzd3 in spinal motor neurons to mediate pathfinding of motor axons innervating the dorsal limb. Celsr3 is expressed in postmitotic neurons in the developing spinal cord. Specific inactivation of Celsr3 in spinal motor neurons severely perturbs peroneal nerve development, leading to absent innervation of the tibialis anterior muscle and stiff hindlimb. Deletion of Celsr3 affects neither the specification of motor neurons nor neuronal survival or neurite outgrowth. Celsr3-deficient axons of the peroneal nerve segregate from those of the tibial nerve but fail to extend dorsally, and they stall just after the branch point of the sciatic nerve. Mutant axons respond to repulsive ephrinA-EphA forward signaling and attractive glial cell–derived neurotrophic factor (GDNF). However, they are insensitive to attractive EphA-ephrinA reverse signaling. In transfected cells, Celsr3 immunoprecipitates with ephrinA2, ephrinA5, Ret, GDNF family receptor a1 (GFRa1) and Fzd3. The function of Celsr3 in motor axons is Fzd3 dependent but Vangl2 independent. Our results thus revealed the crucial roles of Celsr3 and Fzd3 in motor axon guidance, and provide evidence for the first time that the Celsr3-Fzd3 pathway interacts with EphA-ephrinA reverse signaling to guide motor axons in the hindlimb, which may help us better understand their molecular mechanisms of action.
Structural birth defects occur in approximately 3% of live births; most such defects lack defined genetic or environmental causes. Despite advances in surgical approaches, pharmacologic prevention remains largely out of reach.
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