Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAc^CRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAc^CRH neurons during wakefulness and rewarding stimulation. Activation of NAc^CRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAc^CRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAc^CRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAc^CRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.
Animals ; Septal Nuclei/metabolism* ; Nucleus Accumbens/physiology* ; Corticotropin-Releasing Hormone/metabolism* ; Wakefulness/physiology* ; Neurons/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/physiology* ; Anxiety/physiopathology* ; Reward

Neuroglia ; Brain ; Biology

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

With the research progress on the biology and pathogenesis of cancer, immune checkpoint inhibitors (ICIs) have come into being, bringing a new hope for the survival of patients with advanced cancer and opening a new era of cancer immunotherapy. However, with the wide application of immunotherapy in clinical practice, ICI-related adverse events (irAEs) have gradually emerged and are widely known by first-line clinicians. ICIs primarily activate T cells that can attack normal tissues and organs in the body and cause a variety of adverse reactions. Checkpoint inhibitor pneumonitis (CIP) is one of the rare complications with poor prognosis in irAEs. This article reviews the therapeutic mechanism of some ICIs; the incidence, risk factors, pathogenesis, and clinical and imaging manifestations of CIP; and the classification and treatment management of CIP.

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database—cFos-ANAB—a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users’ purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net.

Objective To establish a new patient-derived xenograft (PDX) model of human liver cancer by inoculating the complex of human primary liver cancer cells and a novel microcarrier (microcarrier 6) into mice with normal immune function. Methods Primary liver cancer cells were isolated and extracted from the fresh human liver cancer tissue of five patients and were then co-cultured with microcarrier 6 to construct a three-dimensional tumor cell culture model in vitro . According to the type of graft, 75 male C57BL/6 mice were divided into cell control group, microcarrier control group, and experimental group (each sample corresponded to three groups, with 15 groups in total and 5 mice in each group). The liver cancer cell-microcarrier complex was implanted into the mice by subcutaneous inoculation, and tumor formation time, tumor formation rate, and histopathological manifestations were observed. The Fisher's exact test was used for comparison of categorical data between two groups. Results As for the liver cancer cells from the five patients, tumor formation was observed in the mice corresponding to three patients. In these three experiments, tumor formation was not observed in the control groups and was only observed in the experimental groups, and 12 of the 15 mice in the experimental groups had successful tumor formation, with a tumor formation rate as high as 80%, which was significantly different from that in the cell control groups and the microcarrier control groups (all P < 0.05). The tumor formation time was 5-7 days; the xenograft tumor grew rapidly, and HE staining showed nested or flaky cells with obvious heteromorphism, with the presence of pathological mitosis; immunohistochemical staining showed positive CK8/18, Hep, and Gpc-3, which was in accordance with the characteristics of human liver cancer cells. Conclusion This experiment successfully establishes a new PDX model of human liver cancer based on the complex of microcarrier 6 and human primary liver cancer cells in mice with normal immunity. This model can be used to better elucidate the mechanism of the development and progression of liver cancer in the body with normal immunity, and besides, it also provides a new animal model with higher value for the precise treatment of liver cancer.