GluA1 Degradation by Autophagy Contributes to Circadian Rhythm Effects on Cerebral Ischemia Injury.

The mechanisms of many diseases, including central nervous system disorders, are regulated by circadian rhythms. The development of brain disorders such as depression, autism, and stroke is strongly associated with circadian cycles. Previous studies have shown that cerebral infarct volume is smaller at night (active phase) than during the day (inactive phase) in ischemic stroke rodent models. However, the underlying mechanisms remain unclear. Increasing evidence suggests that glutamate systems and autophagy play important roles in the pathogenesis of stroke. Here, we report that GluA1 expression was decreased and autophagic activity was increased in active-phase male mouse models of stroke compared with the inactive-phase models. In the active-phase model, induction of autophagy decreased the infarct volume, whereas inhibition of autophagy increased the infarct volume. Meanwhile, GluA1 expression was decreased following activation of autophagy and increased following inhibition of autophagy. We used Tat-GluA1 to uncouple p62, an autophagic adapter, from GluA1 and found that this blocked the degradation of GluA1, an effect similar to that of inhibition of autophagy in the active-phase model. We also demonstrated that knock-out of the circadian rhythm gene Per1 abolished the circadian rhythmicity of the volume of infarction and also abolished GluA1 expression and autophagic activity in wild-type (WT) mice. Our results suggest an underlying mechanism by which the circadian rhythm participates in the autophagy-dependent regulation of GluA1 expression, which influences the volume of infarction in stroke.SIGNIFICANCE STATEMENT Circadian rhythms affect the pathophysiological mechanisms of disease. Previous studies suggested that circadian rhythms affect the infarct volume in stroke, but the underlying mechanisms remain largely unknown. Here, we demonstrate that the smaller infarct volume after middle cerebral artery occlusion/reperfusion (MCAO/R) during the active phase is related to lower GluA1 expression and activation of autophagy. The decrease in GluA1 expression during the active phase is mediated by the p62-GluA1 interaction, followed by direct autophagic degradation. In short, GluA1 is the substrate of autophagic degradation, which mainly occurs after MCAO/R during the active phase but not the inactive phase.

Development of Broad-Spectrum Nanobodies for the Therapy and Diagnosis of SARS-CoV-2 and Its Multiple Variants.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evaded the efficacy of previously developed antibodies and vaccines, thus remaining a significant global public health threat. Therefore, it is imperative to develop additional antibodies that are capable of neutralizing emerging variants. Nanobodies, as the smallest functional single-domain antibodies, exhibit enhanced stability and penetration ability, enabling them to recognize numerous concealed epitopes that are inaccessible to conventional antibodies. Herein, we constructed an immune library based on the immunization of alpaca with the S1 subunit of the SARS-CoV-2 spike protein, from which two nanobodies, Nb1 and Nb2, were selected using phage display technology for further characterization. Both nanobodies, with the binding residues residing within the receptor-binding domain (RBD) region of the spike, exhibited high affinity toward the S1 subunit. Moreover, they displayed cross-neutralizing activity against both wild-type SARS-CoV-2 and 10 ο variants, including BA.1, BA.2, BA.3, BA.5, BA.2.75, BF.7, BQ.1, EG.5.1, XBB.1.5, and JN.1. Molecular modeling and dynamics simulations predicted that both nanobodies interacted with the viral RBD through their complementarity determining region 1 (CDR1) and CDR2. These two nanobodies are novel tools for the development of therapeutic and diagnostic countermeasures targeting SARS-CoV-2 variants and potentially emerging coronaviruses.

High serum complement component C4 as a unique predictor of unfavorable outcomes in diabetic stroke.

Previous studies demonstrated that diabetic stroke patients had a poor prognosis and excess complement system activation in the peripheral blood. In this study, the association of serum complement levels with the prognosis of diabetic stroke was examined. Patients with acute ischemic stroke were recruited and were divided into two groups according to their history of diabetes. Baseline data on the admission, including C3 and C4 were collected. Neurologic function at discharge was the primary outcome and was quantified by the National Institutes of Health Stroke Scale (NIHSS). A total of 426 patients with acute ischemic stroke (116 diabetic strokes and 310 non-diabetic strokes) were recruited in this study. There were significant differences between the two groups in hypertension, coronary disease, triglyceride, high-density lipoprotein cholesterol, fasting blood sugar, C4, and mortality rates. Furthermore, the values of complement protein levels were divided into tertiles. In the diabetic stroke group, serum C4 level at the acute phase in the upper third was independently associated with NIHSS score at discharge and concurrent infection. These associations were not significant in non-diabetic stroke. High serum C4 level at admission, as a unique significant predictor, was associated with unfavorable clinical outcomes in the diabetic stroke, independently of traditional risk factors.

Alterations in Regional Homogeneity Assessed by fMRI in Patients with Migraine Without Aura.

The aim of this study was to investigate the alterations in regional homogeneity assessed by fMRI in patients with migraine without aura (MWoA). Fifty-six eligible MWoA patients and 32 matched healthy volunteers were enrolled in this study. MWoA patients were divided into three groups according to the headache days per month within 3 months: infrequent episodic migraine (IEM) group, frequent episodic migraine (FEM) group, and chronic migraine (CM) group. Data collection and rest-state fMRI examination were performed in all cases. The ReHo method was used to analyze the blood oxygen level dependent (BLOD) signals of the adjacent voxels in the brain regions of each patient, and the consistency of their fluctuations in the sequences of same time. Compared with normal controls, ReHo values of bilateral thalami, right insula and right middle temporal gyrus increased and both precentral gyri decreased in the IEM group; ReHo values of bilateral thalami and the right middle temporal gyrus increased; ReHo values of both anterior cingulate cortex, precentral gyri and putamen decreased in the FEM group. Compared with control group, ReHo values of left olfactory cortex, right hippocampus, parahippocampal gyrus, suboccipital gyrus and precuneus increased, both precentral gyri, precuneus, putamen and anterior cingulate cortex decreased in the CM group. Compared with IEM group, ReHo values of both putamen, left middle frontal gyrus, right superior frontal gyrus increased, and the left precuneus decreased in the FEM group. Compared with FEM group, ReHo values of left olfactory and left precuneus increased, and the right superior frontal gyrus, insula, middle temporal gyrus, thalami, both superior temporal gyri decreased in the CM group. In the IEM group, the changes of function focus on the regions associated with coding, conduction and regulation of pain signals. In the FEM group, functional alterations mainly concentrated on the regions associated with pain regulation and emotion cognition. In the CM group, the changes focus on the regions related to spatial attention and cognition, affective disorders and pain feedback, which may be associated with migraine production, development and chronification.

Investigation on pseudorabies prevalence in Chinese swine breeding farms in 2013-2016.

Pseudorabies (PR) has been prevalent in Chinese swine breeding farms since the outbreak at the end of 2011. For investigating current prevalence of PR, a nationwide surveillance has been performed in this study. The swine serum samples were collected from 93, 100, 92, and 91 swine farms in China during 2013-2016, respectively. Since the extensive use of gE-deleted pseudorabies virus (PRV) vaccine, we could apply the PRV-gE antibody for determining wild-type virus infection and the PRV-gB antibody for evaluating vaccine immunization. The results were concluded as follows: (1) Nationally, the positive rate of PRV-gB was maintained at a high level (> 90%), while the positive rate of PRV-gE continued to decrease (from 22.17 to 13.14%). (2) The positive rates of PRV-gE were greatly varied in different geographical regions and swine farms (0~100%), while the positive rate of PRV-gB was generally high (> 90%). (3) The number of imported PRV attenuated vaccines were about twice that of domestic PRV attenuated vaccines, while the positive rate of PRV-gB was not significantly different (P > 0.05). (4) The performance of PR eradication developing or developed farms was better than the performance of common farms, with higher positive rate of PRV-gB (> 90%) and much lower positive rate of PRV-gE (nearly 0%).

Mobilization of Circulating Endothelial Progenitor Cells by dl-3-n-Butylphthalide in Acute Ischemic Stroke Patients.

OBJECTIVE: The research aim was to investigate the effects of dl-3-n-butylphthalide (NBP) on the level of circulating endothelial progenitor cells (EPCs) and clinical outcome in patients with acute ischemic stroke (AIS). MATERIALS AND METHODS: A total of 170 patients were included and randomly assigned to NBP group and control group. All patients were administrated a basic antiplatelet and lipid-lowering therapy. Among the patients, 86 received additional NBP administration for 30 days, whereas 84 received only basic therapy (the control). The level of circulating EPCs (marked with CD34(+)/CD133(+)/KDR(+)) was determined by flow cytometry at baseline and days 7, 14, and 30 after therapy. Impairment of neurological function was evaluated by the National Institutes of Health Stroke Scale (NIHSS) on days 7, 14, 30, and 90 after therapy. The association between the increased level of circulating EPCs and improvement of NIHSS score was evaluated by Pearson analysis. The clinical outcome was evaluated by modified Rankin Scale (mRS) on day 90. During the observation period, any adverse events related to drugs were reported. RESULTS: The levels of circulating EPCs on days 14 and 30 were significantly higher in the NBP group than in the control group. In contrast, NIHSS score was notably lower in NBP group on day 14, 30 and day 90. Pearson correlation analysis revealed a significant association between the increased level of EPCs and improvement of NIHSS score. Also, the mRS score in the NBP group was lower on day 90. Importantly, the reported adverse events in the 2 groups were comparable. CONCLUSION: NBP significantly increases the circulating level and improves clinical outcome in patients with AIS.

Radiological evaluation of anterior lumbar fusion using PEEK cages with adjacent vertebral autograft in spinal deformity long fusion surgeries.

PURPOSE: The aim of this study was to evaluate the radiographic characteristics of polyetheretherketone (PEEK) cages packed with adjacent vertebral autograft material in lumbar anterior lumbar interbody fusion (ALIF) in spinal deformity long fusion surgeries. METHODS: This is a retrospective radiographic study. From April 2008 to April 2012, 40 patients (5 males and 35 females, mean age 67 ± 9 years) with coronal and/or sagittal spine deformities underwent staged corrective surgery combined with lumbar ALIF using PEEK cages at the L3-L4, L4-L5 or L5-S1 segment with posterior long (≥ 4 levels) instrumentation. The mean follow-up time was 27.5 months (13-49 months). We examined the interbody fusion rate and cage subsidence at 3 months postoperatively and final follow-up. Additionally, we evaluated the distance of cage migration at final follow-up and the improvement in lumbar lordosis. The rate of "collapse" of the adjacent vertebra where the autograft was harvested was assessed at the final follow-up. Finally, we examined the cage-related postoperative complications in this series. RESULTS: Solid interbody fusion was achieved in 96.4 % (81/84) of the levels at the final follow-up. A mild forward cage migration was observed, and the mean migration distance at final follow-up was 0.83 mm in L3/4, 0.36 mm in L4/5 and 0.55 mm in L5/S1. There was cage subsidence observed in 8.3 % (7/84) of the levels. In all patients, the PEEK cage maintained a significant increase in segmental lordosis at all postoperative visits. However, a mild reduction in segmental lordosis still occurred with time. The adjacent lumbar vertebral bodies where the autografts were harvested appeared to be intact in height radiologically at the final follow-up. There were no postoperative complications due to bone harvesting or cage insertion. Proximal junctional kyphosis was found in one patient who underwent a subsequent revision surgery. CONCLUSIONS: The use of lumbar ALIF with PEEK cages and adjacent vertebral autografts in spinal deformity long fusion surgeries is an effective and safe procedure. The allograft filler is safe and effective in maintaining the shape of harvested vertebrae. Additional long-term follow-up studies are needed to further justify its use.

Identification and genomic characterization of a novel porcine parvovirus (PPV6) in China.

BACKGROUND: Parvoviruses are classified into two subfamilies based on their host range: the Parvovirinae, which infect vertebrates, and the Densovirinae, which mainly infect insects and other arthropods. In recent years, a number of novel parvoviruses belonging to the subfamily Parvovirinae have been identified from various animal species and humans, including human parvovirus 4 (PARV4), porcine hokovirus, ovine partetravirus, porcine parvovirus 4 (PPV4), and porcine parvovirus 5 (PPV5). METHODS: Using sequence-independent single primer amplification (SISPA), a novel parvovirus within the subfamily Parvovirinae that was distinct from any known parvoviruses was identified and five full-length genome sequences were determined and analyzed. RESULTS: A novel porcine parvovirus, provisionally named PPV6, was initially identified from aborted pig fetuses in China. Retrospective studies revealed the prevalence of PPV6 in aborted pig fetuses and piglets(50% and 75%, respectively) was apparently higher than that in finishing pigs and sows (15.6% and 3.8% respectively). Furthermore, the prevalence of PPV6 in finishing pig was similar in affected and unaffected farms (i.e. 16.7% vs. 13.6%-21.7%). This finding indicates that animal age, perhaps due to increased innate immune resistance, strongly influences the level of PPV6 viremia. Complete genome sequencing and multiple alignments have shown that the nearly full-length genome sequences were approximately 6,100 nucleotides in length and shared 20.5%-42.6% DNA sequence identity with other members of the Parvovirinae subfamily. Phylogenetic analysis showed that PPV6 was significantly distinct from other known parvoviruses and was most closely related to PPV4. CONCLUSION: Our findings and review of published parvovirus sequences suggested that a novel porcine parvovirus is currently circulating in China and might be classified into the novel genus Copiparvovirus within the subfamily Parvovirinae. However, the clinical manifestations of PPV6 are still unknown in that the prevalence of PPV6 was similar between healthy pigs and sick pigs in a retrospective epidemiological study. The identification of PPV6 within the subfamily Parvovirinae provides further insight into the viral and genetic diversity of parvoviruses.

[Levels of Beclin 1 and LC3 in peripheral blood mononuclear cells of patients with multiple sclerosis and neuromyelitis optica and its significance].

OBJECTIVE: To explore the expression and significance of Beclin 1 and LC3 in peripheral blood mononuclear cells (PBMCs) of patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) before and after treatment during acute and recurrent acute phases. METHODS: All outpatients, inpatients and healthy controls were recruited from our hospital from October 2012 to April 2014. During acute phase, PBMCs from patients with multiple sclerosis (MS) and neuromyelitis optica (NMO)(pre and post-treatment) were immediately isolated by Ficoll-Hypaque density gradient centrifugation. And the expressions of Beclin 1 and LC3 were detected by Western blot. And relapsing-remitting MS (RRMS) and relapsing NMO (RNMO) patients were followed up and the expressions of Beclin 1 and LC3 proteins compared during two acute phases. RESULTS: Compared with normal controls, the expression of Beclin 1 in PBMCs from acute phase of MS and NMO patients decreased while the expression of LC3 increased. During acute phase, the expression of Beclin 1 significantly increased after treatment in MS and NMO patients compared with pre-treatment, but the expression of LC3 significantly decreased. The expression of Beclin1 obviously decreased in RRMS and recurrent RNMO compared with the previous period, but the expression of LC3 significantly increased. CONCLUSION: The autophagy level increases in PBMC from MS and NMO patients during acute phase. However it decreases after treatment. However, the autophagy levels significantly increase in RRMS and RNMO. And enhanced autophagy may play its role in the pathogenesis of MS and NMO.

The proteomic analysis uncovers the cellular responses to the African swine fever virus membrane proteins p54, p17, and pB117L.

African swine fever virus (ASFV) infection causes African swine fever (ASF), a highly contagious and fatal disease that poses severe threat to swine production. To gain insights into the host responses to ASFV, we generated recombinant adenovirus Ad5 expressing viral membrane proteins p54, p17, and pB117L individually and infected an alveolar cell line, 3D4/21, with these recombinant viruses. Then, the cell lysates were analyzed using label-free quantification proteomic analysis method. A total of 2158 differentially expressed proteins (DEPs) were identified, of which 817, 466, and 875 proteins were from Ad5-p54-, Ad5-p17-, Ad5-pB117L-infected 3D4/21 cells, respectively. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed distinct yet interconnecting patterns of protein interaction networks. Specifically, the Ad5-p54 virus infection enriched the DEPs primarily involved in the metabolic pathways, endocytosis, adherens junction, and SNARE interactions in vesicular transport. The Ad5-p17 virus infection enriched the DEPs in endocytosis, ubiquitin-mediated proteolysis, N-Glycan biosynthesis, and apoptosis, while the Ad5-pB117L virus infection enriched the DEPs in metabolic pathways, endocytosis, oxidative phosphorylation, and focal adhesion. In summary, these results provide a comprehensive proteinomics analysis of the cellular responses to three ASFV membrane proteins, thus facilitating our understanding of ASFV pathogenesis.

Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion.

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.

A novel porcine circovirus type 2a strain, 10JS-2, with eleven-nucleotide insertions in the origin of genome replication.

Here, we report a novel porcine circovirus type 2a (PCV2a) strain with 11 nucleotides (nt) inserted in the origin of genome replication (Ori). This is the first report of a PCV2a strain with nucleotide insertion in Ori. Our study will help further epidemiological studies and extend our knowledge of evolutionary characteristics of PCV2.

Complete genome sequence of two novel Chinese virulent porcine reproductive and respiratory syndrome virus variants.

A highly pathogenic strain of porcine reproductive and respiratory syndrome virus (PRRSV), characterized by a discontinuous 30-amino-acid deletion in its Nsp2-coding region, has been emerging in China since 2006. Here, we report the complete genomic sequence of two novel Chinese virulent PRRSV variants with additional NSP2-gene deletions, which will help us understand the molecular and evolutionary characteristics of PRRSV in Asia.

Two natural recombinant highly pathogenic porcine reproductive and respiratory syndrome viruses with different pathogenicities.

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is a variant of type 2 PRRSV with high virulence. Genetic and pathogenic characteristics of HP-PRRSV vary rapidly during the evolution. In this study, we determined the complete genome of a HP-PRRSV isolate designated 10FUJ-2, which shared 98.34 % nucleotide identity with HP-PRRSV reference strain JXA1. Genomic analyses by phylogenetic tree and recombination detection program confirmed 10FUJ-2 to be a recombinant with 09JS and JXA1 as potential parental viruses. Furthermore, we identified that 10FUJ-2 has high virulence as similar as the parental viruses by animal challenge study. In addition, we found that SY0909 was also a recombination virus probably from JXA1 and NT0801, which has been reported to be low pathogenic. Recombination analysis also revealed that Glycoproteins GP2 to GP5 of HP-PRRSV might contain major virulence determinants. Identification of two natural recombinants with different virulence supports the notion that recombination is a driving force affecting HP-PRRSV pathogenicity and a common mechanism contributing to HP-PRRSV evolution.

Daridorexant for the treatment of insomnia disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Daridorexant is a novel dual orexin receptor antagonist that has shown efficacy as a treatment for insomnia in multiple randomized clinical trials. However, the efficacy and safety of daridorexant for treatment of insomnia disorder has not been characterized comprehensively in the literature. Therefore, we performed a meta-analysis of available studies. We performed a meta-analysis to systematically evaluate the efficacy and safety of daridorexant for treatment of insomnia disorder. METHODS: MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials were systematically searched up to February 2022. Relative risk and standard mean difference were used to evaluate clinical outcomes. RESULTS: We pooled 2271 patients from 4 randomized clinical trials, and evaluated efficacy endpoints. We found that 50 mg of daridorexant was superior to placebo for 4 efficacy outcomes including wake time after sleep onset, latency to persistent sleep, subjective total sleep time, and Insomnia Daytime Symptoms and Impacts Questionnaire domain score (P < .05). In addition, there were no significant differences (P > .05) in adverse events between daridorexant and placebo. CONCLUSIONS: Different dosages of daridorexant were tested for treatment of insomnia; however, 5 and 10 mg are not available because of issues of suboptimal effectiveness. Daridorexant showed better efficacy and safety for treatment of insomnia disorder at doses of 25 and 50 mg.

Effect of collateral circulation in patients with multiple craniocervical artery stenoses.

Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long-term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro-basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743-0.857, p < 0.001; Tan scores: OR: 0.478, 95% CI: 0.336-0.679, p < 0.001). Meanwhile, the collateral circulation scores were significantly associated with the recurrence of AIS within 3 years (rLMC scores: OR: 0.926, 95% CI: 0.860-0.997, p = 0.042; Tan scores: OR: 0.467, 95% CI: 0.306-0.712, p < 0.001). Most associations remained significant in the subgroup of patients with VBA stenosis. Favorable collateral circulation in multiple craniocervical artery stenosis patients reduced long-term ischemic event recurrence. Stratifying treatment risks is essential for optimizing outcomes.

Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke.

Synaptotagmin III (Syt3) is a Ca2+-dependent membrane-traffic protein that is highly concentrated in synaptic plasma membranes and affects synaptic plasticity by regulating post-synaptic receptor endocytosis. Here, we show that Syt3 is upregulated in the penumbra after ischemia/reperfusion (I/R) injury. Knockdown of Syt3 protects against I/R injury, promotes recovery of motor function, and inhibits cognitive decline. Overexpression of Syt3 exerts the opposite effects. Mechanistically, I/R injury augments Syt3-GluA2 interactions, decreases GluA2 surface expression, and promotes the formation of Ca2+-permeable AMPA receptors (CP-AMPARs). Using a CP-AMPAR antagonist or dissociating the Syt3-GluA2 complex via TAT-GluA2-3Y peptide promotes recovery from neurological impairments and improves cognitive function. Furthermore, Syt3 knockout mice are resistant to cerebral ischemia because they show high-level expression of surface GluA2 and low-level expression of CP-AMPARs after I/R. Our results indicate that Syt3-GluA2 interactions, which regulate the formation of CP-AMPARs, may be a therapeutic target for ischemic insults.

The changes of brainstem auditory evoked potentials (BAEP) after vertebrobasilar artery ischemia in rabbits.

Brainstem auditory evoked potentials (BAEPs) have been used as a valuable neurophysiologic index of neuronal dysfunction in the level of the brainstem. BAEPs are also useful in subdividing evoked potentials into normal, slight, or pronounced in patients with vertebrobasilar insufficiency. We investigated the changes of BAEP after vertebrobasilar artery ischemia in rabbits and its significance in clinical work. A brainstem ischemic model was made by unilateral extracranial occlusion of vertebral artery to monitor BAEPs at 0, 10, 20, 30, 40, 50, and 60 min after occlusion. We found that peak latencies (PL) of I, III, and most notably V were gradually extended. In addition, we observed a significant (P < 0.05) delay of interpeak latencies (IPL) of waves I­III, III­V, and I­V after occlusion. This delay became more significant in IPL I­V 60 min after occlusion. Our results also demonstrate that the amplitude of I and V had no obvious change (P < 0.05). In the rabbit with bilateral extracranial occlusion of vertebral artery, BAEP waveforms disappeared 10 min after occlusion. Our results showed that vertebrobasilar insufficiency caused brainstem ischemia, which induced BAEP abnormity. Taken together, our findings suggest that BAEP has important significance for the clinical diagnosis of vertebrobasilar insufficiency. Therefore, early detection of neuronal change after transient cerebral ischemia is important in initiating treatment within the therapeutic window.