Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery.

Early-stage postoperative depression and anxiety following orthognathic surgery: a cross-sectional study.

Background: The objective of this study was to observe the incidence and potential risk factors of postoperative depression and anxiety in patients during the early period after undergoing orthognathic surgery.

Methods: From March 7 to September 7, 2023, patients ≥ 18 years of age who were scheduled for elective orthognathic surgery under general anesthesia in Peking University School and Hospital of Stomatology were included in this study. We prospectively evaluated their degrees of pre- and postoperative depression and anxiety using the Patient Health Questionnaire-9 and the State Trait Anxiety Inventory.

Lidocaine Spray for Acute Postsurgical Pain Control After Posterior Pharyngeal Flap Surgery.

Objectives: This study evaluated the use of lidocaine spray for acute postsurgical pain control after posterior pharyngeal flap surgery.

Methods: Fifty patients aged 4 to 14 years who were scheduled to undergo elective posterior pharyngeal flap surgery were randomized to receive 2.4% lidocaine spray (Group L) or an identical volume of placebo spray (Group C) on the surgical field at the end of the surgery.

Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke.

Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders.

Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke.

Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke.

Nos1 and Nos1 excitatory neurons in the BLA regulate anxiety- and depression-related behaviors oppositely.

Background: The basolateral amygdala (BLA) neurons are primarily glutamatergic and have been associated with emotion regulation. However, little is known about the roles of BLA neurons expressing neuronal nitric oxide synthase (nNOS, Nos1) in the regulation of emotional behaviors.

Methods: Using Nos1cre mice and chemogenetic and optogenetic manipulations, we specifically silenced or activated Nos1 or Nos1 neurons in the BLA, or silenced their projections to the anterdorsal bed nucleus of the stria terminalis (adBNST) and ventral hippocampus (vHPC).

Ketone bodies promote stroke recovery via GAT-1-dependent cortical network remodeling.

Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that β-hydroxybutyrate (β-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase.

Enhanced AMPAR-dependent synaptic transmission by S-nitrosylation in the vmPFC contributes to chronic inflammatory pain-induced persistent anxiety in mice.

Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively.

Self-organization of kinetochore-fibers in human mitotic spindles.

During eukaryotic cell division, chromosomes are linked to microtubules (MTs) in the spindle by a macromolecular complex called the kinetochore. The bound kinetochore microtubules (KMTs) are crucial to ensuring accurate chromosome segregation. Recent reconstructions by electron tomography (Kiewisz et al.

Prenatal Isoflurane Exposure Induces Developmental Neurotoxicity in Rats: the Role of Gut Microbiota.

Fetal exposure to inhaled anesthetics, such as isoflurane, may lead to neurodevelopmental impairment in offspring. Yet, the mechanisms of prenatal isoflurane-induced developmental neurotoxicity have not been fully elucidated. Gut microbiota is a pivotal modulator of brain development and functions.

A pain killer without analgesic tolerance designed by co-targeting PSD-95-nNOS interaction and α2-containning GABARs.

Overactivation of N-methyl-D-aspartate receptor (NMDAR) in the spinal cord dorsal horn (SDH) in the setting of injury represents a key mechanism of neuropathic pain. However, directly blocking NMDAR or its downstream signaling, interaction between postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS), causes analgesic tolerance, mainly due to GABAergic disinhibition. The aim of this study is to explore the possibility of preventing analgesic tolerance through co-targeting NMDAR downstream signaling and γ-aminobutyric acid type A receptors (GABARs).

Neuronal Nitric Oxide Synthase in Nucleus Accumbens Specifically Mediates Susceptibility to Social Defeat Stress through Cyclin-Dependent Kinase 5.

Stress-induced depression is common worldwide. NAc, a "reward" center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized.

Dorsal Hippocampus to Infralimbic Cortex Circuit is Essential for the Recall of Extinction Memory.

Posttraumatic stress disorder subjects usually show impaired recall of extinction memory, leading to extinguished fear relapses. However, little is known about the neural mechanisms underlying the impaired recall of extinction memory. We show here that the activity of dorsal hippocampus (dHPC) to infralimbic (IL) cortex circuit is essential for the recall of fear extinction memory in male mice.

Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval.

The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval.

Prolonged Use of NMDAR Antagonist Develops Analgesic Tolerance in Neuropathic Pain via Nitric Oxide Reduction-Induced GABAergic Disinhibition.

Neuropathic pain is usually persistent due to maladaptive neuroplasticity-induced central sensitization and, therefore, necessitates long-term treatment. N-methyl-D-aspartate receptor (NMDAR)-mediated hypersensitivity in the spinal dorsal horn represents key mechanisms of central sensitization. Short-term use of NMDAR antagonists produces antinociceptive efficacy in animal pain models and in clinical practice by reducing central sensitization.

Probing and manipulating embryogenesis via nanoscale thermometry and temperature control.

Understanding the coordination of cell-division timing is one of the outstanding questions in the field of developmental biology. One active control parameter of the cell-cycle duration is temperature, as it can accelerate or decelerate the rate of biochemical reactions. However, controlled experiments at the cellular scale are challenging, due to the limited availability of biocompatible temperature sensors, as well as the lack of practical methods to systematically control local temperatures and cellular dynamics.

Shikani Optical Stylet for Awake Nasal Intubation in Patients Undergoing Head and Neck Surgery.

Objectives: To evaluate the efficacy and safety of the Shikani optical stylet (SOS) versus fiberoptic bronchoscope (FOB) for awake nasal intubation in head and neck surgery patients with an anticipated difficult airway.

Study Design: Prospective randomized clinical trial.

Methods: This study involved 50 adult patients scheduled for elective head and neck surgery and presented with an anticipated difficult airway.

nNOS-expressing neurons in the vmPFC transform pPVT-derived chronic pain signals into anxiety behaviors.

Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models.

Central-spindle microtubules are strongly coupled to chromosomes during both anaphase A and anaphase B.

Spindle microtubules, whose dynamics vary over time and at different locations, cooperatively drive chromosome segregation. Measurements of microtubule dynamics and spindle ultrastructure can provide insight into the behaviors of microtubules, helping elucidate the mechanism of chromosome segregation. Much work has focused on the dynamics and organization of kinetochore microtubules, that is, on the region between chromosomes and poles.