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Frontiers in Neural Circuits 2023Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved... (Review)
Review
Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.
Topics: Cerebral Cortex; Neurogenesis; Interneurons; Cell Movement
PubMed: 37779671
DOI: 10.3389/fncir.2023.1256455 -
Translational Andrology and Urology Oct 2023Premature ejaculation (PE) is a common sexual disorder among male adults and negatively impacts a man's sexual life. Currently, the mainstay treatment of PE is still... (Review)
Review
BACKGROUND AND OBJECTIVE
Premature ejaculation (PE) is a common sexual disorder among male adults and negatively impacts a man's sexual life. Currently, the mainstay treatment of PE is still medical therapy which has drawbacks among patients as a consequence of side effects. Despite the new definitions, the evolution of medical therapy, and the consensus for the management of PE, it remains challenging to treat for many clinicians especially when medical treatment fails. However, the International Society for Sexual Medicine (ISSM) and the American Urological Association (AUA) guidelines ignored surgical therapy due to conflicting medical reports and doubts about the safety of surgical management. This article discusses the surgical management of PE based on recent guidelines, reviews, and evolving techniques.
METHODS
We reviewed the literature using PubMed and searched for the following keywords: premature ejaculation, selective dorsal neurectomy, hyaluronic acid, dorsal nerve neuromodulation, cryo-ablation of the dorsal nerve and inner condom technique until May 2023. Seventeen studies were found.
KEY CONTENT AND FINDINGS
Even though the widespread use of many surgical modalities in Asia such as glans penis augmentation (GPA) using hyaluronic acid (HA) selective dorsal neurectomy (SDN), cryo-ablation of the dorsal nerve, neuromodulation of the dorsal nerve (NMDN), and circumcision are still considered as controversial for the guidelines.
CONCLUSIONS
The mainstay treatment of PE is still pharmaceutical. However, the current body of evidence on surgical treatments for PE is limited. Men considering surgical therapy for PE should be counseled well for the risks and benefits as there may be chronic disabilities. Further, well-designed trials are needed to establish safety and efficacy for the surgical treatment.
PubMed: 37969778
DOI: 10.21037/tau-23-240 -
Journal of Clinical Neurophysiology :... Feb 2024The majority of cases of dorsal rhizotomy surgeries in children are done to improve the spasticity associated with cerebral palsy, and more recent techniques are... (Review)
Review
The majority of cases of dorsal rhizotomy surgeries in children are done to improve the spasticity associated with cerebral palsy, and more recent techniques are selective in nature and referred to as selective dorsal rhizotomy (SDR). The techniques applied to selective dorsal rhizotomy surgery has changed since it was first described and continues to undergo modifications. Approaches to surgery and monitoring vary slightly among centers. This article provides a review of the rationale, variety of surgical approaches, and intraoperative neurophysiologic monitoring methods used along with discussion of the risks, complications and outcomes in these surgeries.
Topics: Child; Humans; Rhizotomy; Muscle Spasticity; Cerebral Palsy; Intraoperative Neurophysiological Monitoring; Treatment Outcome
PubMed: 38306221
DOI: 10.1097/WNP.0000000000001041 -
Frontiers in Immunology 2023Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid...
BACKGROUND AND OBJECTIVES
Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid receptor (NMDAR) encephalitis (NMDARE), characterized by serum and/or spinal fluid NMDAR antibodies, is the most common form of autoimmune encephalitis (AE). A translational rodent NMDARE model would allow for pathophysiologic studies of AE, leading to advances in the diagnosis and treatment of this debilitating neuropsychiatric disorder. The main objective of this work was to identify optimal active immunization conditions for NMDARE in mice.
METHODS
Female C57BL/6J mice aged 8 weeks old were injected subcutaneously with an emulsion of complete Freund's adjuvant, killed and dessicated , and a 30 amino acid peptide flanking the NMDAR GluN1 subunit N368/G369 residue targeted by NMDARE patients' antibodies. Three different induction methods were examined using subcutaneous injection of the peptide emulsion mixture into mice in 1) the ventral surface, 2) the dorsal surface, or 3) the dorsal surface with reimmunization at 4 and 8 weeks (boosted). Mice were bled biweekly and sacrificed at 2, 4, 6, 8, and 14 weeks. Serum and CSF NMDAR antibody titer, mouse behavior, hippocampal cell surface and postsynaptic NMDAR cluster density, and brain immune cell entry and cytokine content were examined.
RESULTS
All immunized mice produced serum and CSF NMDAR antibodies, which peaked at 6 weeks in the serum and at 6 (ventral and dorsal boosted) or 8 weeks (dorsal unboosted) post-immunization in the CSF, and demonstrated decreased hippocampal NMDAR cluster density by 6 weeks post-immunization. In contrast to dorsally-immunized mice, ventrally-induced mice displayed a translationally-relevant phenotype including memory deficits and depressive behavior, changes in cerebral cytokines, and entry of T-cells into the brain at the 4-week timepoint. A similar phenotype of memory dysfunction and anxiety was seen in dorsally-immunized mice only when they were serially boosted, which also resulted in higher antibody titers.
DISCUSSION
Our study revealed induction method-dependent differences in active immunization mouse models of NMDARE disease. A novel ventrally-induced NMDARE model demonstrated characteristics of AE earlier compared to dorsally-induced animals and is likely suitable for most short-term studies. However, boosting and improving the durability of the immune response might be preferred in prolonged longitudinal studies.
Topics: Mice; Female; Animals; Emulsions; Mice, Inbred C57BL; Encephalitis; Antibodies; Receptors, N-Methyl-D-Aspartate; Vaccination; Disease Models, Animal; Autoimmune Diseases of the Nervous System
PubMed: 37520559
DOI: 10.3389/fimmu.2023.1177672 -
Neuroscience Apr 2024In males but not in females, brain derived neurotrophic factor (BDNF) plays an obligatory role in the onset and maintenance of neuropathic pain. Afferent terminals of... (Review)
Review
In males but not in females, brain derived neurotrophic factor (BDNF) plays an obligatory role in the onset and maintenance of neuropathic pain. Afferent terminals of injured peripheral nerves release colony stimulating factor (CSF-1) and other mediators into the dorsal horn. These transform the phenotype of dorsal horn microglia such that they express P2X4 purinoceptors. Activation of these receptors by neuron-derived ATP promotes BDNF release. This microglial-derived BDNF increases synaptic activation of excitatory dorsal horn neurons and decreases that of inhibitory neurons. It also alters the neuronal chloride gradient such the normal inhibitory effect of GABA is converted to excitation. By as yet undefined processes, this attenuated inhibition increases NMDA receptor function. BDNF also promotes the release of pro-inflammatory cytokines from astrocytes. All of these actions culminate in the increase dorsal horn excitability that underlies many forms of neuropathic pain. Peripheral nerve injury also alters excitability of structures in the thalamus, cortex and mesolimbic system that are responsible for pain perception and for the generation of co-morbidities such as anxiety and depression. The weight of evidence from male rodents suggests that this preferential modulation of excitably of supra-spinal pain processing structures also involves the action of microglial-derived BDNF. Possible mechanisms promoting the preferential release of BDNF in pain signaling structures are discussed. In females, invading T-lymphocytes increase dorsal horn excitability but it remains to be determined whether similar processes operate in supra-spinal structures. Despite its ubiquitous role in pain aetiology neither BDNF nor TrkB receptors represent potential therapeutic targets.
Topics: Rats; Animals; Female; Male; Rats, Sprague-Dawley; Brain-Derived Neurotrophic Factor; Posterior Horn Cells; Spinal Cord Dorsal Horn; Neuralgia; Hyperalgesia
PubMed: 38417539
DOI: 10.1016/j.neuroscience.2024.02.020 -
JAMA Dermatology May 2024
PubMed: 38776072
DOI: 10.1001/jamadermatol.2024.1029 -
Journal of Foot and Ankle Research Sep 2023Surgical resection of Morton's neuroma includes dorsal and plantar approaches. However, there is no consensus on the choice of approach in clinic. The purpose of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical resection of Morton's neuroma includes dorsal and plantar approaches. However, there is no consensus on the choice of approach in clinic. The purpose of this study was to conduct a systematic review and meta-analysis to compare the surgical results of dorsal and plantar approaches.
METHODS
The literatures of PubMed, Cochrane library, Embase and Web of Science were searched on April 26th, 2023. A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The data were extracted after screening the literature and evaluating the quality of the methodology included in the study. The RevMan5.4 software was used to analyze and calculate the OR value and 95% confidence interval.
RESULTS
A total of 7 randomized controlled trials and comparative studies were published, of which only 5 were included. There were 158 feet via plantar approach (plantar group, PG) and 189 via dorsal approach (dorsal group, DG). There was no significant difference between PG and DG in overall adverse events, sensory problems, incision infection and deep vein thrombosis (p > 0.05). In terms of scar problems, PG showed more than DG (OR, 2.90[95%CI, 1.40 to 5.98]; p = 0.004). Other outcome indicators such as visual analogue scale (VAS) scores and American Orthopedic Foot and Ankle Society (AOFAS) scores were difficult to be included in the comparison.
CONCLUSIONS
Based on the relatively low quality and small amount of available evidence, the meta-analysis conducted produces a hypothesis that the frequency of adverse events in surgical treatment of Morton's neuroma, dorsal approach and plantar approach may be the same, but the types are different. More high-level evidence is needed to further verify this hypothesis.
Topics: Humans; Morton Neuroma; Consensus; Lower Extremity; Orthopedics; Software
PubMed: 37674248
DOI: 10.1186/s13047-023-00660-w