Publications by authors named "Aoling Cai"

8 Publications

  • Page 1 of 1

Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations.

J Clin Invest 2021 04;131(8)

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

BACKGROUNDThe coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease's long-term effects on the brain still need to be explored.METHODSWe recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed.RESULTSCompared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6.CONCLUSIONIndirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19-related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19.FUNDINGNatural Science Foundation of China.
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http://dx.doi.org/10.1172/JCI147329DOI Listing
April 2021

Neuronal mechanisms of adenosine A receptors in the loss of consciousness induced by propofol general anesthesia with functional magnetic resonance imaging.

J Neurochem 2021 Mar 6;156(6):1020-1032. Epub 2020 Sep 6.

Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China.

Propofol is the most common intravenous anesthetic agent for induction and maintenance of anesthesia, and has been used clinically for more than 30 years. However, the mechanism by which propofol induces loss of consciousness (LOC) remains largely unknown. The adenosine A receptor (A R) has been extensively proven to have an effect on physiological sleep. It is, therefore, important to investigate the role of A R in the induction of LOC using propofol. In the present study, the administration of the highly selective A R agonist (CGS21680) and antagonist (SCH58261) was utilized to investigate the function of A R under general anesthesia induced by propofol by means of animal behavior studies, resting-state magnetic resonance imaging and c-Fos immunofluorescence staining approaches. Our results show that CGS21680 significantly prolonged the duration of LOC induced by propofol, increased the c-Fos expression in nucleus accumbens (NAc) and suppressed the functional connectivity of NAc-dorsal raphe nucleus (DR) and NAc-cingulate cortex (CG). However, SCH58261 significantly shortened the duration of LOC induced by propofol, decreased the c-Fos expression in NAc, increased the c-Fos expression in DR, and elevated the functional connectivity of NAc-DR and NAc-CG. Collectively, our findings demonstrate the important roles played by A R in the LOC induced by propofol and suggest that the neural circuit between NAc-DR maybe controlled by A R in the mechanism of anesthesia induced by propofol.
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http://dx.doi.org/10.1111/jnc.15146DOI Listing
March 2021

Investigation of robust visual reaction and functional connectivity in the rat brain induced by rocuronium bromide with functional MRI.

Am J Transl Res 2020 15;12(6):2396-2408. Epub 2020 Jun 15.

Center of Brain Science, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences Wuhan 430071, Hubei, P. R. China.

Functional magnetic resonance imaging (fMRI) has been used extensively to understand the brain function of a wide range of neurological and psychiatric disorders. When applied to animal studies, anesthesia is always used to reduce the movement of the animal and also reduce the impacts on the results of fMRI. Several awake models have been proposed by applying physical animal movement restrictions. However, restraining devices were designed for individual subject which limits the promotion of fMRI in awake animals. Here, a clinical muscle relaxant rocuronium bromide (RB) was introduced to restrain the animal in fMRI scanning time. The fMRI reactions of the animal induced with RB and the other two commonly used anesthesia protocols were investigated. The results of the fMRI showed that there were increased functional connectivity and well-round visual responses in the RB induced state. Furthermore, significant BOLD signal changes were found in the cortex and thalamus regions when the animal revived from isoflurane, which should be essential to further understand the effects of anesthesia on the brain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344061PMC
June 2020

A new GABAergic somatostatin projection from the BNST onto accumbal parvalbumin neurons controls anxiety.

Mol Psychiatry 2020 Jun 18. Epub 2020 Jun 18.

Shenzhen Key Lab of Neuropsychiatric Modulation, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS); Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.

The prevailing view is that parvalbumin (PV) interneurons play modulatory roles in emotional response through local medium spiny projection neurons (MSNs). Here, we show that PV activity within the nucleus accumbens shell (sNAc) is required for producing anxiety-like avoidance when mice are under anxiogenic situations. Firing rates of sNAc neurons were negatively correlated to exploration time in open arms (threatening environment). In addition, sNAc neurons exhibited high excitability in a chronic stress mouse model, which generated excessive maladaptive avoidance behavior in an anxiogenic context. We also discovered a novel GABAergic pathway from the anterior dorsal bed nuclei of stria terminalis (adBNST) to sNAc neurons. Optogenetic activation of these afferent terminals in sNAc produced an anxiolytic effect via GABA transmission. Next, we further demonstrated that chronic stressors attenuated the inhibitory synaptic transmission at adBNST → sNAc synapses, which in turn explains the hyperexcitability of sNAc PV neurons on stressed models. Therefore, activation of these GABAergic afferents in sNAc rescued the excessive avoidance behavior related to an anxious state. Finally, we identified that the majority GABAergic input neurons, which innervate sNAc cells, were expressing somatostatin (SOM), and also revealed that coordination between SOM- and PV- cells functioning in the BNST → NAc circuit has an inhibitory influence on anxiety-like responses. Our findings provide a potentially neurobiological basis for therapeutic interventions in pathological anxiety.
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http://dx.doi.org/10.1038/s41380-020-0816-3DOI Listing
June 2020

Dynamic Changes of Functional Neuronal Activities Between the Auditory Pathway and Limbic Systems Contribute to Noise-Induced Tinnitus with a Normal Audiogram.

Neuroscience 2019 06 1;408:31-45. Epub 2019 Apr 1.

Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address:

Tinnitus is thought to be triggered by aberrant neural activity in the central auditory pathway and is often accompanied by comorbidities of emotional distress and anxiety, which imply maladaptive functional connectivity to limbic structures, such as the amygdala and hippocampus. Tinnitus patients with normal audiograms can also have accompanying anxiety and depression, clinically. To test the role of functional connectivity between the central auditory pathway and limbic structures in patients with tinnitus with normal audiograms, we developed a murine noise-induced tinnitus model with a temporary threshold shift (TTS). Tinnitus mice exhibited reduced auditory brainstem response wave I amplitude, and an enhanced wave IV amplitude and wave IV/I amplitude ratio, as compared with control and non-tinnitus mice. Resting-state functional magnetic resonance imaging (fMRI) was used to identify abnormal connectivity of the amygdala and hippocampus and to determine the relationship with tinnitus characteristics. We found increased fMRI responses with amplitude of low-frequency fluctuation (ALFF) in the auditory cortex and decreased ALFF in the amygdala and hippocampus at day 1, but decreased ALFF in the auditory cortex and increased ALFF in the amygdala at day 28 post-noise exposure in tinnitus mice. Decreased functional connectivity between auditory brain regions and limbic structures was demonstrated at day 28 in tinnitus mice. Therefore, aberrant neural activities in tinnitus mice with TTS involved not only the central auditory pathway, but also limbic structures, and there was maladaptive functional connectivity between the central auditory pathway and limbic structures, such as the amygdala and hippocampus.
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http://dx.doi.org/10.1016/j.neuroscience.2019.03.054DOI Listing
June 2019

Effect of myocardial ischemic preconditioning on ischemia-reperfusion stimulation-induced activation in rat thoracic spinal cord with functional MRI.

Int J Cardiol 2019 06 14;285:59-64. Epub 2019 Mar 14.

Department of Anesthesiology, the Second Hospital of Anhui Medical University, 230601 Hefei, PR China. Electronic address:

Background: Myocardial ischemia and reperfusion-evoked spinal reflexes involve nociceptive signals that trigger neuronal excitation through cardiac afferents, projecting into the thoracic spinal cord. Ischemic preconditioning (IPC) involves brief episodes of sublethal ischemia and reperfusion enhances the resistance of the myocardium to subsequent ischemic insults. This study investigated the effects of IPC on ischemia-reperfusion (I/R) stimulation-induced activation in the thoracic spinal cord of rats.

Methods: A new remotely controlled I/R model was established. The infarct size was determined as a percentage of area at risk (IS/AAR) and arrhythmia scores were evaluated. Non-invasive in vivo fMRI was used for signal quantitative analysis of thoracic spinal spatiotemporal. The role of IPC on the excitability of substantia gelatinosa (SG) neurons was assessed by spinal patch clamp recording technique. The altered expressions of c-Fos, SP, and CGRP in T segment were detected by immunohistochemical staining.

Results: The novel I/R model was induced successfully and reliably utilized, and IPC treatment markedly reduced the myocardial infarct size. fMRI analysis revealed that IPC reduced the increased BOLD signals induced by prolonged ischemia-reperfusion. Patch clamp recording showed that IPC treatment reversed the enhanced excitability of SG neurons during I/R treatment. The results of immunofluorescent staining indicated that IPC mitigated the I/R-induced dramatic increase of c-Fos, and reduced the release of SP and CGRP in dorsal horns of spinal cord.

Conclusions: These results suggested that IPC suppressed neuronal activation induced by I/R stimuli in rat thoracic spinal cord using spinal cord fMRI and patch clamp recording techniques.
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http://dx.doi.org/10.1016/j.ijcard.2019.03.025DOI Listing
June 2019

Circular RNA Transcriptomic Analysis of Primary Human Brain Microvascular Endothelial Cells Infected with Meningitic Escherichia coli.

Mol Ther Nucleic Acids 2018 Dec 26;13:651-664. Epub 2018 Oct 26.

The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address:

With their essential regulatory roles in gene expression and high abundance in the brain, circular RNAs (circRNAs) have recently attracted considerable attention. Many studies have shown that circRNAs play important roles in the pathology of CNS diseases, but whether circRNAs participate in E. coli-induced bacterial meningitis is unclear. We used high-throughput sequencing to analyze the transcriptional profiles of host circRNAs in primary brain microvascular endothelial cells in response to meningitic E. coli. A total of 308 circRNAs were significantly altered, including 140 upregulated and 168 downregulated ones (p < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology enrichment of the parental genes of these altered circRNAs indicated that they are likely to be involved in diverse biological processes via influencing the expression of their parental genes. Coupled with our previous mRNA and microRNA sequencing data, a competing endogenous RNA analysis was performed, and the potential regulatory network was preliminarily constructed and validated. By revealing the transcriptional profiles of the host circRNAs involved in E. coli meningitis, it is envisaged that the novel insight gained into the regulatory mechanisms of circRNAs in the development of bacterial meningitis will lead to better understanding of how to prevent and treat bacterial CNS infections.
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http://dx.doi.org/10.1016/j.omtn.2018.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258830PMC
December 2018

Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier.

Oncotarget 2016 Sep;7(39):63839-63855

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Escherichia coli is the most common Gram-negative bacterium that possesses the ability to cause neonatal meningitis, which develops as circulating bacteria penetrate the blood-brain barrier (BBB). However, whether meningitic E. coli could induce disruption of the BBB and the underlying mechanisms are poorly understood. Our current work highlight for the first time the participation of VEGFA and Snail-1, as well as the potential mechanisms, in meningitic E. coli induced disruption of the BBB. Here, we characterized a meningitis-causing E. coli PCN033, and demonstrated that PCN033 invasion could increase the BBB permeability through downregulating and remodeling the tight junction proteins (TJ proteins). This process required the PCN033 infection-induced upregulation of VEGFA and Snail-1, which involves the activation of TLR2-MAPK-ERK1/2 signaling cascade. Moreover, production of proinflammatory cytokines and chemokines in response to infection also promoted the upregulation of VEGFA and Snail-1, therefore further mediating the BBB disruption. Our observations reported here directly support the involvement of VEGFA and Snail-1 in meningitic E. coli induced BBB disruption, and VEGFA and Snail-1 would therefore represent the essential host targets for future prevention of clinical E. coli meningitis.
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http://dx.doi.org/10.18632/oncotarget.11696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325408PMC
September 2016