Neurotic

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The blood-brain barrier (BBB) presents a formidable challenge in delivering therapeutic agents to the central nervous system. Ultrasound-mediated BBB disruption has emerged as a promising non-invasive technique to enhance drug delivery to the brain. This manuscript reviews fundamental principles of ultrasound-based techniques and their mechanisms of action in temporarily permeabilizing the BBB. Clinical trials employing ultrasound for BBB disruption are discussed, summarizing diverse applications ranging from the treatment of neurodegenerative diseases to targeted drug delivery for brain tumors...

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses...

PURPOSE: Corneal neurotization is an emerging technique that offers potential for visual rehabilitation in neurotrophic keratopathy. This study reports on a multicenter experience and outcomes for both direct and indirect methods of corneal neurotization. METHODS: Retrospective case series. Sixteen patients with neurotrophic keratopathy who underwent corneal neurotization across 5 centers in Australia and Israel were identified for inclusion. Corneal neurotization was performed via direct neurotization from the ipsilateral or contralateral supraorbital/supratrochlear nerve or by the use of an interpositional sural nerve graft...

The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye...

Deep brain stimulation (DBS) is an established therapeutic tool for the treatment of Parkinson's disease (PD). The mechanisms of DBS for PD are likely rooted in modulation of the subthalamo-pallidal network. However, it can be difficult to electrophysiologically interrogate that network in human patients. The recent identification of large amplitude evoked potential (EP) oscillations from DBS in the subthalamic nucleus (STN) or globus pallidus internus (GPi) are providing new scientific opportunities to expand understanding of human basal ganglia network activity...

OBJECTIVES: Central sensitivity (CS) is defined as an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold inputs. CS has recently been linked to the psychological burden associated with chronic pain, such as fibromyalgia (FM). The primary objective of this study is to investigate the impact of specific psychological constructs on CS in patients with FM. In Study 1, we explore the influence of temperament, personality, childhood trauma, defence mechanisms, and mental pain on CS...

Positive modulation of hepatocyte growth factor (HGF) signaling may represent a promising therapeutic strategy for Alzheimer's disease (AD) based on its multimodal neurotrophic, neuroprotective, and anti-inflammatory effects addressing the complex pathophysiology of neurodegeneration. Fosgonimeton is a small-molecule positive modulator of the HGF system that has demonstrated neurotrophic and pro-cognitive effects in preclinical models of dementia. Herein, we evaluate the neuroprotective potential of fosgonimeton, or its active metabolite, fosgo-AM, in amyloid-beta (Aβ)-driven preclinical models of AD, providing mechanistic insight into its mode of action...

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among the diseases related to mitochondrial dysfunction, Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss and neuroinflammation. Recently, it was reported that mitochondrial transfer between cells occurred naturally and that exogenous mitochondrial transplantation was beneficial for treating mitochondrial dysfunction...

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 ​Hz ("gamma") and lesser power in frequency bands lower than 30 ​Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time...

Deep Brain Stimulation (DBS) has become a pivotal therapeutic approach for Parkinson's Disease (PD) and various neuropsychiatric conditions, impacting over 200,000 patients. Despite its widespread application, the intricate mechanisms behind DBS remain a subject of ongoing investigation. This article provides an overview of the current knowledge surrounding the local, circuit, and neurobiochemical effects of DBS, focusing on the subthalamic nucleus (STN) as a key target in PD management. The local effects of DBS, once thought to mimic a reversible lesion, now reveal a more nuanced interplay with myelinated axons, neurotransmitter release, and the surrounding microenvironment...

Postural instability is a detrimental and often treatment-refractory symptom of Parkinson's disease. While many existing studies quantify the biomechanical deficits among various postural domains (static, anticipatory, and reactive) in this population, less is known regarding the neural network dysfunctions underlying these phenomena. This review will summarize current studies on the cortical and subcortical neural activities during postural responses in healthy subjects and those with Parkinson's disease...

Driven by the scarcity of effective treatment options in clinical settings, the present study aimed to identify a new potential target for Alzheimer's disease (AD) treatment. We focused on Lars2, an enzyme synthesizing mitochondrial leucyl-tRNA, and its role in maintaining mitochondrial function. Bioinformatics analysis of human brain transcriptome data revealed downregulation of Lars2 in AD patients compared to healthy controls. During in vitro experiments, the knockdown of Lars2 in mouse neuroblastoma cells (neuro-2a cells) and primary cortical neurons led to morphological changes and decreased density in mouse hippocampal neurons...

BACKGROUND: Skin-grafted free gracilis muscle flaps are commonly used for lower extremity reconstruction. However, the loss of sensory function may lead to increased patient morbidity. This study prospectively analyzed the sensory and neuropathic pain outcomes of neurotized skin-grafted free gracilis muscle flaps used for the reconstruction of lower extremity defects. METHODS: Patients undergoing lower extremity reconstructions between 2020 and 2022 with neurotized skin-grafted free gracilis muscle flaps were prospectively enrolled...

Berberine (BBR) has demonstrated potent anti-inflammatory effects by modulating macrophage polarization. Nevertheless, the precise mechanisms through which berberine regulates post-injury inflammation within the peripheral nerve system remain elusive. This study seeks to elucidate the role of BBR and its underlying mechanisms in inflammation following peripheral nerve injury (PNI). Adult male C57BL/6J mice subjected to PNI were administered daily doses of berberine (0, 60, 120, 180, 240 ​mg/kg) via gavage from day 1 through day 28...

BACKGROUND: Sub-health can have an impact on the physical condition of the youth adults, and this study aimed to investigate the influencing factors of sub-health related to the Big Five personality in the Chinese youth adults. METHODS: A multi-stage random sampling method was used to survey young adults. A moderated mediation analysis was conducted to investigate how overall sleep quality and family health influenced the relationship between youth with different personalities and sub-health...

The individual's mental health crisis and the COVID-19 pandemic lead to mental disorders. The transmission of the COVID-19 virus is associated with the levels of anxiety, stress, and depression in individuals, similar to other factors. Increases in mental illness cases and the prevalence of depression have peaked after the pandemic struck. The limited social intervention, reduced communication, peer support, and increased social isolation during the pandemic resulted in higher levels of depression, stress, and anxiety which leads to mental illness...

PURPOSE: Breast anesthesia after mastectomy and reconstruction has been an ongoing concern with few improvements made in recent years. At present, there is a lack of studies evaluating the impact of comorbidities on sensation restoration. Identifying risk factors (RF) will be helpful with preoperative counseling. METHODS: This was a prospective study on patients who underwent mastectomy and immediate implant-based or neurotized deep inferior epigastric perforator (DIEP) flap-based reconstruction...

PURPOSE: Loss of breast sensation after mastectomy has been well documented. Postoperative reinnervation of the breast is influenced by factors including reconstructive technique, patient comorbidities, and adjuvant treatment. However, little attention has been paid to the differences in sensation across regions of the breast and the impact of reconstructive method on these regional differences over time. METHODS: Patients undergoing nipple-sparing mastectomy with immediate autologous or alloplastic reconstruction were prospectively followed...

BACKGROUND: Free nipple grafting makes sensory recovery challenging. Permanent decreased sensation to touch and temperature in skin-grafted skin is common. Direct neurotization of the nipple-areolar complex (NAC) graft has been described. However, quantitative data regarding degree of nipple reinnervation possible is unknown. This study aims to quantify and qualify sensation recovery following nerve coaptation to reinnervate the NAC. METHODS: Patients undergoing mastectomy for gender dysphoria from 2020 to 2022 were offered nerve allograft to restore nipple sensation...