The Irritable Bowel Syndrome: How Stress Can Affect the Amygdala Activity and the Brain-Gut Axis

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Rat pro-inflammatory cytokine and cytokine related mRNA quantification by real-time polymerase chain reaction using SYBR green

BACKGROUND: Cytokine mRNA quantification is widely used to investigate cytokine profiles, particularly in small samples. Real-time polymerase chain reaction is currently the most reliable method of quantifying low-level transcripts such as cytokine and cytokine receptor mRNAs. This accurate technique allows the quantification of a larger pattern of cytokines than quantification at the protein level, which is limited to a smaller number of proteins. RESULTS: Although fluorogenic probes are considered more sensitive than fluorescent dyes, we have developed SYBR Green real-time RT-PCR protocols to assay pro-inflammatory cytokines (IL1a, IL1b and IL6, TNFa), cytokine receptors (IL1-r1, IL1-r2, IL6-r, TNF-r2) and related molecules (IL1-RA, SOCS3) mRNA in rats. This method enables normalisation against several housekeeping genes (beta-actin, GAPDH, CypA, HPRT) dependent on the specific experimental treatments and tissues using either standard curve, or comparative C(T )quantification method. PCR efficiency and sensitivity allow the assessment of; i) basal mRNA levels in many tissues and even decreases in mRNA levels, ii) mRNA levels from very small samples. CONCLUSION: Real-time RT-PCR is currently the best way to investigate cytokine networks. The investigations should be completed by the analysis of genes regulated by cytokines or involved in cytokine signalling, providing indirect information on cytokine protein expression

Spectrum of neural electrical activity in guinea pig cochlea: effects of anaesthesia regimen, body temperature and ambient noise.

International audienceSpectral analysis of electric noise recorded from the round window of the cochlea is thought to represent the summed spontaneous activity of the auditory nerve. It has been postulated that it could provide a possible tinnitus index. Because experimental conditions could change this neural activity, the effect of anaesthesia regimen, body temperature and ambient noise on the spectrum of spontaneous neural noise (SNN) were investigated in guinea pig cochlea. SNN was studied in awake guinea pigs and after anaesthesia with pentobarbital (P), xylazine/ketamine (XK) or xylazine/tiletamine-zolazepam (XTZ). Body temperature varied gradually from 33 to 41 degrees C under XK regimen. In awake animals, broadband noise was generated with intensity varying from 0 to 50 dB. The SNN consisted in a broad peak at approximately 900 Hz. With ambient broadband noise, it increased exponentially with the sound level with no shift in frequency. Soon after anaesthetic induction, the lowest frequencies were constantly decreased, and gradually the 900 Hz peak either increased moderately (P) or dropped steeply (XTZ) or remained unchanged (XK). Peak frequency increased linearly with body temperature whereas the amplitude reached a maximum at around 39.5 degrees C. In conclusion, these data indicate that experimental conditions such as anaesthesia regimen, body temperature and ambient noise modify the spontaneous neural outflow of the cochlea and must be taken into account when studying SNN

Therapeutic efficacy of intra-cochlear administration of methylprednisolone after acoustic trauma caused by gunshot noise in guinea pigs.

International audienceThe therapeutic efficacy of cochlear infusion of methylprednisolone (MP) after an impulse noise trauma (170dB SPL peak) was evaluated in guinea pigs. The compound action potential threshold shifts were measured over a 14 days recovery period after the gunshot exposure. For each animal, one of the cochlea was perfused directly into the scala tympani with MP during 7 days via a mini-osmotic pump, whereas the other cochlea was not pump-implanted. The functional study of hearing was supplemented by histological analysis. Forty eight hours after the trauma, significant differences between auditory threshold shifts in the implanted and non-implanted ears were observed for frequencies above 8kHz. At day 7, the difference was significant for only one frequency and no difference was observed after 14 days recovery. Cochleograms showed that the hair cell losses were significantly lower in the MP treated ears. This work indicates that direct infusion of MP into perilymphatic space accelerates hearing recovery, reduces hair cell losses after impulse noise trauma but does not limit permanent threshold shifts

Comparison of the oxime-induced reactivation of rhesus monkey, swine and guinea pig erythrocyte acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity.

International audienceRecently, a dynamically working in vitro model with real-time determination of membrane-bound human acetylcholinesterase (AChE) activity was shown to be a versatile model to investigate oxime-induced reactivation kinetics of organophosphate- (OP) inhibited enzyme. In this assay, AChE was immobilized on particle filters which were perfused with acetylthiocholine, Ellman's reagent and phosphate buffer. Subsequently, AChE activity was continuously analyzed in a flow-through detector. Now, it was an intriguing question whether this model could be used with erythrocyte AChE from other species in order to investigate kinetic interactions in the absence of annoying side reactions. Rhesus monkey, swine and guinea pig erythrocytes were a stable and highly reproducible enzyme source. Then, the model was applied to the reactivation of sarin- and paraoxon-inhibited AChE by obidoxime or HI 6 and it could be shown that the derived reactivation rate constants were in good agreement to previous results obtained from experiments with a static model. Hence, this dynamic model offers the possibility to investigate highly reproducible interactions between AChE, OP and oximes with human and animal AChE

Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway.

International audienceBACKGROUND: The brain and the gut communicate bidirectionally through the autonomic nervous system (ANS). The vagus nerve (VN), a major component of the ANS, plays a key role in the neuro-endocrine-immune axis to maintain homeostasia through its afferents (through the activation of the hypothalamic pituitary adrenal axis and the central ANS) and through its efferents (i.e. the cholinergic anti-inflammatory pathway; CAP). The CAP has an anti-TNF effect both through the release of acetylcholine at the distal VN acting on macrophages and through the connection of the VN with the spleen through the splenic sympathetic nerve. Vagus nerve stimulation (VNS) of vagal afferents at high frequency (20-30 Hz) is used for the treatment of drug-resistant epilepsy and depression. Low-frequency (5 Hz) VNS of vagal efferents activates the CAP for an anti-inflammatory effect that is as an anti-TNF therapy in inflammatory diseases were TNF is a key cytokine as represented by experimental sepsis, postoperative ileus, burn-induced intestinal barrier injury, colitis. However, both vagal afferents and efferents are activated by VNS. PURPOSE: The objective of this review was to explore the following: (i) the supporting evidence for the importance of VNS in epilepsy (and depression) and its mechanisms of action, (ii) the anti-inflammatory characteristics of the VN, (iii) the experimental evidence that VNS impact on inflammatory disorders focusing on the digestive tract, and (iv) how VNS could potentially be harnessed therapeutically in human inflammatory disorders such as inflammatory bowel diseases, irritable bowel syndrome, postoperative ileus, rheumatoid arthritis as an anti-inflammatory therapy

Successful endovascular treatment of three fusiform cerebral aneurysms with the Pipeline Embolization Device in a patient with dilating HIV vasculopathy.

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Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: effect of an NF-kappaB inhibitor.

International audiencePURPOSE: The pathologic changes within the intestinal muscle layer may be at the origin of the cytokines that account for acute radiation-induced inflammation. We were specifically interested in evaluating the efficacy of an inhibitor of nuclear transcription factor kappa B (NF-kappaB) activation that is involved in regulating cytokine expression. METHODS AND MATERIALS: Cytokine expression was analyzed in the ileal muscularis layer by reverse transcriptase-polymerase chain reaction (RT-PCR) at 3 h, 6 h, and 3 days after a 10-Gy gamma whole-body irradiation of rats. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally (30 mg/kg) 15 min before irradiation and once a day for 3 days. RESULTS: Interleukin (IL)-1beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 mRNA increased at 3 h and 6 h after irradiation, and expression of IL-6 and IL-8 was elevated at 3 days. On the other hand, levels of the anti-inflammatory cytokine IL-10 were markedly lower on Day 3. Overexpression of IL-6 on Day 3 was combined with upregulation of the IL-6 receptors (gp130/gp80) and suppressor of cytokine signaling-3 (SOCS3) genes. CAPE treatment did not significantly change IL-1beta or TNF-alpha expressions in the irradiated rats; it increased IL-10 expression at 6 h but had no effect on it on Day 3. CAPE treatment inhibited the radiation-induced expression of IL-6, IL-6 receptors (IL-6rs), and SOCS3 at 3 days. CONCLUSION: In vivo, irradiation induced a cascade of inflammatory responses that involved the transcription factor NF-kappaB; this inflammation was reduced by CAPE treatment

Dynamic Causal Modelling and physiological confounds: a functional MRI study of vagus nerve stimulation.: DCM of Vagus Nerve Stimulation in fMRI

International audienceDynamic Causal Modelling (DCM) has been proposed to estimate neuronal connectivity from functional magnetic resonance imaging (fMRI) using a biophysical model that links synaptic activity to hemodynamic processes. However, it is well known that fMRI is sensitive not only to neuronal activity, but also to many other psychophysiological responses which may be task-related, such as changes in cardio-respiratory activity. They are not explicitly taken into account in the generative models of DCM and their effects on estimated neuronal connectivity are not known. The main goal of this study was to report the face validity of DCM in the presence of strong physiological confounds that presumably cannot be corrected for, using an fMRI experiment of vagus nerve stimulation (VNS) performed in rats. First, a simple simulation was used to evaluate the principled ability of DCM to recover directed connectivity in the presence of a confounding factor. Second, we tested the experimental validity using measures of the BOLD correlates of left 5Hz VNS. Because VNS mostly activates the central autonomic regulation system, fMRI signals were likely to represent both direct and indirect vascular responses to such activation. In addition to the inference of standard statistical parametric maps, DCM was thus used to estimate directed neural connectivity in a small brain network including the nucleus tractus solitarius (NTS) known to receive vagal afferents. Though blood pressure changes may constitute a major physiological confound in this dataset, model comparison of DCMs still allowed the identification of the NTS as the input station of the VNS pathway to the brain. Our study indicates that current developments of DCM are robust to psychophysiological responses to some extent, but does not exclude the need to develop specific models of brain - body interactions within the DCM framework to better estimate neuronal connectivity from fMRI time series

Occlusion of vertebral artery due to transverse canal osteochondroma

International audienceOsteochondroma is a non-rare benign osseous neoplasm[1] that is often observed within the posterior arch of vertebrae.Vascular compression may be observed because of thisexuberant bone formation [2]. Vertebral artery compressionin transverse canal is exceptional. We report on a case ofvertebral artery occlusion related to compressive osteochondroma,responsible for acute stroke in the vertebrobasilarsystem