Reprogramming rat astrocytes into neurons using small molecules for cell replacement following intracerebral hemorrhage

Astrocytes are promising source cells to replace neurons lost to disease owing to a shared lineage and capacities for dedifferentiation and proliferation under pathological conditions. Reprogramming of astrocytes to neurons has been achieved by transcription factor modulation, but reprogramming in vitro or in vivo using small‐molecule drugs may have several advantages for clinical application. For instance, small molecules can be extensively characterized for efficacy, toxicity, and tumorigenicity in vitro; induce rapid initiation and subsequent reversal of transdifferentiation upon withdrawal, and obviate the need for exogenous gene transfection. Here we report a new astrocyte–neuron reprogramming strategy using a combination of small molecules (0.5 mM valproic acid, 1 μM RepSox, 3 μM CHIR99021, 2 μM I‐BET151, 10 μM ISX‐9, and 10 μM forskolin). Treatment with this drug combination gradually reduced expression levels of astroglial marker proteins (glial fibrillary acidic protein and S100), transiently enhanced expression of the neuronal progenitor marker doublecortin, and subsequently elevated expression of the mature neuronal marker NeuN in primary astrocyte cultures. These changes were accompanied by transition to a neuron‐like morphological phenotype and expression of multiple neuronal transcription factors. Further, this drug combination induced astrocyte‐to‐neuron transdifferentiation in a culture model of intracerebral hemorrhage (ICH) and upregulated many transdifferentiation‐associated signaling molecules in ICH model rats. In culture, the drug combination also reduced ICH model‐associated oxidative stress, apoptosis, and pro‐inflammatory cytokine production. Neurons derived from small‐molecule reprogramming of astrocytes in adult Sprague–Dawley rats demonstrated long‐term survival and maintenance of neuronal phenotype. This small‐molecule‐induced astrocyte‐to‐neuron transdifferentiation method may be a promising strategy for neuronal replacement therapy.

Bioreactance-guided fluid therapy for excision of a giant brain tumor in an infant under general anesthesia: A case report and literature review

Pediatric patients are more likely to suffer from brain tumors. Surgical resection is often the optimal treatment. Perioperative management of pediatric brain tumor resection brings great challenges to anesthesiologists, especially for fluid therapy. In this case, the infant-patient was only 69-day-old, weighed 6 kg，but she was facing a gaint brain tumor (7.9 cm × 8.1 cm × 6.7 cm) excision. The infant was at great risks such as hemorrhagic shock, cerebral edema, pulmonary edema, congestive heart failure, coagulation dysfunction, etc. However, we tried to use the parameters obtained by bioreactance-based NICOM® device (Cheetah Medical) to guide the infant’s intraoperative fluid therapy, and successfully avoided these complications and achieved a good prognosis.

Neuroprotective effects of adipose‐derived stem cells on ferrous sulfate‐induced neurotoxicity

Background: Ferrous ion, a degradation product of hematomas, induces inflammatory reactions and other secondary injuries after intracerebral hemorrhage (ICH). Our study aimed to investigate the specific neuroprotective mechanism of adipose‐derived stem cells (ADSCs) on ferrous ion‐induced neural injury in vitro. Methods: ADSCs were co‐cultured with primary cortical neurons in a transwell system treated with ferrous sulfate to generate an in vitro ICH model. ADSCs and cortical neurons were cultured in the upper and lower chambers, respectively. Neuron apoptosis was determined by flow cytometry. The levels of insulin‐like growth factor‐1 (IGF‐1), malondialdehyde (MDA) and nitric oxide synthase (NOS) activity in neuron culture medium were detected with commercial kits. In neurons, protein expression in phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway, nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase‐1 (HO‐1) signaling pathway and apoptosis‐related proteins were detected by western blot. Results: ADSCs attenuated neural apoptosis, reduced MDA levels and NOS activity induced by ferrous sulfate. In neurons, IGF‐1 was increased, as were p‐PI3K, p‐Akt, Nrf2, HO‐1, and Bcl‐2 while cleaved caspase 3 was down‐regulated. Conclusions: ADSCs exert neuroprotective effects against ferrous iron‐induced neuronal damage by secreting IGF‐1 and increasing the levels of Akt‐dependent Nrf2/ARE signaling pathway.

Sleep‐based therapy: A new treatment for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a worldwide problem with no effective treatment. Patients usually die of respiratory failure. The basic pathological process of ALS is the degeneration and necrosis of motor neurons. Neuroglial cell dysfunction is considered closely related to the development of ALS. Sleep plays an important role in repairing the nervous system, and sleep disorders can worsen ALS. Herein, we review the pathogenesis of ALS and the neuroprotective mechanism of sleep‐based therapy. Sleep‐based therapy could be a potential strategy to treat ALS.

Advances in the study of nervous system infections in COVID‐19

Shortly after its outbreak, coronavirus disease 2019 (COVID‐19) has very rapidly spread to become a global epidemic. Early clinical findings mainly included typical symptoms such as fever and cough with a very high transmission rate. Recent findings have demonstrated neurological manifestations of atypical symptoms, which is associated with poor prognosis. In this paper, we describe the neurological aspects of COVID‐19 pneumonia in terms of relevant neurons, virus‐associated receptors, and olfactory and neurological clinical manifestations and offer insights on treatment.

Magnetic resonance imaging for smoking abstinence: symptoms, mechanisms, and interventions

Tobacco smoking is the leading preventable cause of morbidity and mortality worldwide. Although a number of smokers are aware of the adverse outcomes of smoking and express a strong desire to stop smoking, most smoking quit attempts end in relapse within the first few days of abstinence, primarily resulting from the aversive aspects of the nicotine withdrawal syndrome. Therefore, studying the neural mechanisms of smoking abstinence, identifying smokers with heightened relapse vulnerability prior to quit attempts, and developing effective smoking cessation treatments appear to be promising strategies for improving the success of quit attempts. In recent years, with the development of magnetic resonance imaging, the neural substrates of smoking abstinence have become extensively studied. In this review, we first introduce the psychophysiological changes induced by smoking abstinence, including affective, cognitive, and somatic signs. We then provide an overview of the magnetic resonance imaging-based evidence regarding abstinence-related functional changes accompanied by these psychophysiological changes. We conclude with a discussion of the neural markers that could predict relapse during quit attempts and a summary of the psychophysiological interventions that are currently often used to help with smoking cessation. This review extends our understanding of the role of the central nervous system in smoking abstinence.

Correlations between cognitive function and gray matter alterations in patients with acute lacunar stroke

Researchers emphasized acute lacunar stroke (ALS) patients suffer from poor social/physical outcomes, cognitive decline, and decreased quality of life. We hypothesized brain abnormalities may occur in ALS during this particular stage and may be associated with cognitive deficits upon evaluation. We investigated structural abnormalities in ALS using magnetic resonance imaging and voxel-based morphometry conducted on 28 healthy controls (HC) and 29 patients with ALS and proximal anterior circulation occlusion within 12 hours of symptom onset. Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive dysfunction. Decreased gray matter (GM) in ALS vs. HC was predominantly in the superior frontal gyrus, inferior frontal gyrus, insula, superior temporal gyrus (STG), heschl gyrus, middle temporal gyrus (MTG), posterior cingulate cortex (PCC), hippocampus (HIP), and others. Positive correlation was found between GM density and MMSE scores in STG ( r = 0.59, p = 0.0007), MTG ( r = 0.46, p = 0.01), PCC ( r = 0.42, p = 0.02), HIP ( r = 0.4, p = 0.03), and medial prefrontal cortex ( r = 0.5, p = 0.005). This study provided further information on pathophysiological/morphological mechanisms related to cognitive impairment in ALS and is the basis for further studies in aging-related diseases.

Quantitative analysis of cerebrovascular characteristics of Parkinson’s disease treated with acupuncture based on magnetic resonance angiography

Background: Acupuncture has become an important alternative clinical treatment for Parkinson’s disease (PD), but its efficacy and the underlying mechanisms remain debatable. Using a newly developed magnetic resonance angiography (MRA) method that has higher sensitivity for smaller and distal vessels and a novel tool that can trace vessels and extract vascular features, the immediate effects of acupuncture on intracranial vessels and blood flow in patients with PD as well as correlations with clinical outcomes were quantitatively evaluated. Methods: Fifteen PD patients received acupuncture at the Dazhui and Fengchi acupoint positions. MRA was performed before and after 30 min of treatment. The cerebral blood flow (CBF) and the length, volume, diameter, and signal intensity of the intracranial internal carotid artery (ICA) and middle cerebral artery (MCA) were measured. The Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) and Visual Analogue Scale (VAS) were used to evaluate the motor symptoms and the subjective feelings of discomfort. Results: Acupuncture significantly reduced UPDRS-III and VAS scores. No significant changes were noted in the overall CBF before and after treatment. However, there was a significant extension effect on the length of the intracranial ICA and MCA and the distal MCA, and a significant increase in the number of branches of the MCA was found. Although acupuncture tended to increase the total volume of the intracranial ICA and the volume of the MCA, no statistical significance was reached. The total intensity was not altered, but the intensity and diameter of the M1 segment were significantly increased, whereas the intensity of the MCA was decreased. A positive correlation between M1 intensity changes and UPDRS-III changes was found. Conclusions: Angiographic evaluation suggested that acupuncture had a significant effect on intracranial blood vessels, which is one possible mechanism for acupuncture improving the motor symptoms of PD.

Hippocampal resting-state functional connectivity with the mPFC and DLPFC moderates and mediates the association between education level and memory function in subjective cognitive decline

Objective: This study aims to determine the relationship between education level, memory function, and hippocampus functional and structural alterations in subjective cognitive decline (SCD). Methods: Seventy-five participants with SCD were divided into high education (HE) and low education (LE) level groups. A Wechsler Memory Scale–Chinese Revision test and functional and structural MRI were performed within 1 week after participant recruitment. The bilateral hippocampus resting-state functional connectivity (rsFC), gray matter volume (GMV) of brain regions identified by rsFC analysis, and moderating and mediating effects were assessed. Results: Compared with the LE group, HE individuals showed 1) higher memory quotient (MQ) and Digit Span subscore, 2) decreased hippocampal rsFC with the right medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (DLPFC), and 3) increased GMV in the right mPFC and DLPFC. The bilateral hippocampus–right DLPFC rsFC significantly associated with the MQ and the bilateral hippocampus–right mPFCrsFC with the Digit Span subscore in each group. The bilateral hippocampus–right DLPFC rsFC moderated the relationship between the education level and MQ. The bilateral hippocampus–right mPFC rsFC mediated the relationship between the education level and Digit Span subscore in all subjects. Conclusion: The hippocampal rsFC with the right mPFC and DLPFC contributes to the education level effect on memory function in SCD.