In recent years, the incidence of autism spectrum disorder (ASD) has increased, but the etiology and pathogenesis remain unclear. In this narrative review, we review and systematically summarize the methods used to construct animal models to study ASD and the related behavioral studies based on recent literature. Utilization of various ASD animal models can complement research on the etiology, pathogenesis, and core behaviors of ASD, providing information and a foundation for further basic research and clinical treatment of ASD.

Arteriovenous fistulas (AVFs) have long been used as dialysis access in patients with end-stage renal disease; however, their maturation and long-term patency still fall short of clinical needs. Rodent models are irreplaceable to facilitate the study of mechanisms and provide reliable insights into clinical problems. The ideal rodent AVF model recapitulates the major features and pathology of human disease as closely as possible, and pre-induction of the uremic milieu is an important addition to AVF failure studies. Herein, we review different surgical methods used so far to create AVF in rodents, including surgical suturing, needle puncture, and the cuff technique. We also summarize commonly used evaluations after AVF placement. The aim was to provide recent advances and ideas for better selection and induction of rodent AVF models. At the same time, further improvements in the models and a deeper understanding of AVF failure mechanisms are expected.

Despite known drawbacks, rodent models are essential tools in the research of renal development, physiology, and pathogenesis. In the past decade, rodent models have been developed and used to mimic different etiologies of acute kidney injury (AKI), AKI to chronic kidney disease (CKD) transition or progression, and AKI with comorbidities. These models have been applied for both mechanistic research and preclinical drug development. However, current rodent models have their limitations, especially since they often do not fully recapitulate the pathophysiology of AKI in human patients, and thus need further refinement. Here, we discuss the present status of these rodent models, including the pathophysiologic compatibility, clinical translational significance, key factors affecting model consistency, and their main limitations. Future efforts should focus on establishing robust models that simulate the major clinical and molecular phenotypes of human AKI and its progression.

Neuropathic pain (NP) is a common chronic pain condition resulted from lesions or diseases of somatosensory nervous system, but the pathogenesis remains unclear. A growing body of evidence supports the relationship between pathogenesis and N6-methyladenosine (m6A) modifications of RNA. However, studies on the role of m6A modifications in NP are still at an early stage. Elucidating different etiologies is important for understanding the specific pathogenesis of NP. This article provides a comprehensive review on the role of m6A methylation modifications including methyltransferases (\"writers\"), demethylases (\"erasers\"), and m6A binding proteins (\"readers\") in NP models. Further analysis of the pathogenic mechanism relationship between m6A and NP provided novel theoretical and practical significance for clinical treatment of NP.

Appropriate treatment options are lacking for hepatitis E virus (HEV)-infected pregnant women and immunocompromised individuals. Thus, we aimed to identify efficient anti-HEV drugs through high-throughput screening, validate them in vitro and in vivo (in a preclinical animal study), and elucidate their underlying antiviral mechanism of action.
Using appropriate cellular and rodent HEV infection models, we studied a critical pathway for host-HEV interactions and performed a preclinical study of the corresponding antivirals, which target proteostasis of the HEV replicase.
We found 17 inhibitors that target HEV-HSP90 interactions by unbiased compound library screening on human hepatocytes harboring an HEV replicon. Inhibitors of HSP90 (iHSP90) markedly suppressed HEV replication with efficacy exceeding that of conventional antivirals (IFNα and ribavirin) in vitro. Mechanistically, iHSP90 treatment released the viral replicase ORF1 protein from the ORF1-HSP90 complex and triggered rapid ubiquitin/proteasome-mediated degradation of ORF1, resulting in abrogated HEV replication. Furthermore, a preclinical trial in a Mongolian gerbil HEV infection model showed this novel anti-HEV strategy to be safe, efficient, and able to prevent HEV-induced liver damage.
In this study, we uncover a proteostatic pathway that is critical for host-HEV interactions and we provide a foundation from which to translate this new understanding of the HEV life cycle into clinically promising antivirals.
Appropriate treatment options for hepatitis E virus (HEV)-infected pregnant women and immunocompromised patients are lacking; hence, there is an urgent need for safe and effective HEV-specific therapies. This study identified new antivirals (inhibitors of HSP90) that significantly limit HEV infection by targeting the viral replicase for degradation. Moreover, these anti-HEV drugs were validated in an HEV rodent model and were found to be safe and efficient for prevention of HEV-induced liver injury in preclinical experiments. Our findings substantially promote the understanding of HEV pathobiology and pave the way for antiviral development.

Spinal cord injury (SCI) often has devastating consequences for the patient\'s physical, mental and occupational health. At present, there is no effective treatment for SCI, and appropriate animal models are very important for studying the pathological manifestations, injury mechanisms, and corresponding treatment. However, the pathological changes in each injury model are different, which creates difficulties in selecting appropriate models for different research purposes. In this article, we analyze various SCI models and introduce their pathological features, including inflammation, glial scar formation, axon regeneration, ischemia-reperfusion injury, and oxidative stress, and evaluate the advantages and disadvantages of each model, which is convenient for selecting suitable models for different injury mechanisms to study therapeutic methods.

Hashimoto\'s thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis.
Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined.
HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons.
Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.

Infarct size is associated with stroke severity in clinical studies, so reducing it has become an important target and research hotspot in the treatment of ischemic stroke. Some preclinical studies have shown transcranial direct current stimulation (tDCS) reduced infarct size and improved neurological deficit, but others have not found beneficial effects. Besides, the optimal pattern of tDCS for ischemic stroke remains largely unknown. To shed light on the current circumstance and future research directions, the systematic review evaluated the effect of different tDCS paradigms in reducing infarct size and improving neurological deficit in rodent models of ischemic stroke and assessed the methodological quality of current literature. We searched the MEDLINE (via PubMed), EMBASE, Web of Science, and Scopus from their inception to August 18, 2021, to identify studies evaluating the effects of tDCS in rodent models of ischemic stroke. Eight studies were included, of which seven studies were included in the meta-analysis. The results showed cathodal tDCS, rather than anodal tDCS, reduced infarct size mainly measured by tetrazolium chloride and magnetic resonance imaging (standardized mean difference: -1.13; 95% CI: -1.72, -0.53; p = 0.0002) and improved neurological deficit assessed by a modified neurological severity score (standardized mean difference: -2.10; 95% CI: -3.78, -0.42; p = 0.01) in an early stage of focal ischemic stroke in rodent models. Subgroup analyses showed effects of cathodal tDCS on infarct size were not varied by ischemia duration (ischemia for 1, 1.5, and 2 h or permanent ischemia) and anesthesia (involving isoflurane and ketamine). The overall quality of studies included was low, thus the results must be interpreted cautiously. Published studies suggest that cathodal tDCS may be a promising avenue to explore for augmenting rehabilitation from focal ischemic stroke. Considering the methodological limitations, it is unreliable to blindly extrapolate the animal data to the clinical practice. Future research is needed to investigate the mechanism of tDCS in a randomized and blinded fashion in clinically relevant stroke models, such as elderly animals, female animals, and animals with comorbidities, to find an optimal treatment protocol.

Cardiac arrest (CA) is the leading cause of death in humans. Research has shown that mild therapeutic hypothermia (MTH) can reduce neurological sequelae and mortality after CA. Nevertheless, the mechanism remains unclear. This study aimed to determine whether MTH promotes neurogenesis, attenuates neuronal damage, and inhibits apoptosis of neurons in rats after CA. Sprague-Dawley rats were divided into the normothermia and mild hypothermia groups. The rats in the normothermia and hypothermia groups were exposed to 2 h of normothermia (36-37℃) and hypothermia (32-33℃), respectively, immediately after resuscitation from 5 min of asphyxial CA. Corresponding control groups not subjected to CA were included. On days 1-6, 5-bromodeoxyuridine (BrdU) 100 mg/kg/day was administered intraperitoneally. The animals were euthanized 1 week after CA. Compared with the normothermia group, the hypothermia group showed a significant increase in the number of doublecortin (DCX) immune-positive cells in the subgranular zone of the hippocampus 1 week after CA. Neurogenesis was assessed using double immunofluorescent labeling of BrdU with neuronal-specific nuclear protein (NeuN)/DCX. There was no marked change in the number of newborn mature (BrdU+-NeuN+) neurons, though there was a significant increase in the number of newborn immature (BrdU+-DCX+) neurons in the hypothermia than in the normothermia group 1 week after CA. Neuronal injury and apoptosis in the CA1 region of the hippocampus, assessed using NeuN immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays, were significantly reduced in the hypothermia group 1 week after CA. Moreover, mild hypothermia increased the expression of cold-shock protein RNA-binding motif protein 3 (RBM3) in the early stage (24 h/48 h) after CA. These results suggested that mild hypothermia promotes generation of neuronal cells, reduces neuronal injury, and inhibits apoptosis of neurons, which may be related to RBM3 expression.

Breast cancer is a highly complicated disease. Advancement in the treatment and prevention of breast cancer lies in elucidation of the mechanism of carcinogenesis and progression. Rodent models of breast cancer have developed into premier tools for investigating the mechanisms and genetic pathways in breast cancer progression and metastasis and for developing and evaluating clinical therapeutics. Every rodent model has advantages and disadvantages, and the selection of appropriate rodent models with which to investigate breast cancer is a key decision in research. Design of a suitable rodent model for a specific research purpose is based on the integration of the advantages and disadvantages of different models. Our purpose in writing this review is to elaborate on various rodent models for breast cancer formation, progression, and therapeutic testing.