Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size

<p>Abstract</p> <p>Background</p> <p>Systemic inflammation impairs outcome in stroke patients and experimental animals via mechanisms which are poorly understood. Circulating inflammatory mediators can activate cerebrovascular endothelium or glial cells in the brain and impact on ischaemic brain injury. One of the most serious early clinical complications of cerebral ischaemia is brain oedema, which compromises survival in the first 24-48 h. It is not understood whether systemic inflammatory challenges impair outcome after stroke by increasing brain injury only or whether they have direct effects on brain oedema, cerebrovascular inflammation and blood-brain barrier damage.</p> <p>Methods</p> <p>We used two different systemic inflammatory stimuli, acute endotoxin treatment and anaphylaxis to study mechanisms of brain injury after middle cerebral artery occlusion (MCAo). Ischaemic brain injury, blood-brain barrier damage and oedema were analysed by histological techniques. Systemic cytokine responses and inflammatory changes in the brain were analysed by cytometric bead array, immunofluorescence, <it>in situ </it>hibridization and quantitative real-time PCR.</p> <p>Results</p> <p>Systemic inflammatory challenges profoundly impaired survival in the first 24 h after experimental stroke in mice, independently of an increase in infarct size. Systemic lipopolysaccharide (LPS) dose-dependently increased mortality (50-100%) minutes to hours after cerebral ischaemia. Acute anaphylactic challenge in ovalbumin-sensitised mice affected stroke more seriously when induced via intraperitoneal administration compared to intravenous. Both LPS and anaphylaxis induced inflammatory changes in the blood and in the brain prior to experimental stroke. Plasma cytokine levels were significantly higher after LPS, while increased IL-10 levels were seen after anaphylaxis. After MCAo, both LPS and anaphylaxis increased microglial interleukin-1α (IL-1α) expression and blood-brain barrier breakdown. LPS caused marked granulocyte recruitment throughout the ipsilateral hemisphere. To investigate whether reduction of ischaemic damage can improve outcome in systemic inflammation, controlled hypothermia was performed. Hypothermia reduced infarct size in all treatment groups and moderately improved survival, but failed to reduce excess oedema formation after anaphylaxis and LPS-induced neuroinflammation.</p> <p>Conclusions</p> <p>Our results suggest that systemic inflammatory conditions induce cerebrovascular inflammation via diverse mechanisms. Increased brain inflammation, blood-brain barrier injury and brain oedema formation can be major contributors to impaired outcome in mice after experimental stroke with systemic inflammatory stimuli, independently of infarct size.</p

Differential Changes in Expression of Stress- and Metabolic-related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal

Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH), urocortin 2 (UCN2) and proopiomelanocortin (POMC) compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15-30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY) and arginine vasopressin (AVP) mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls

A versengés jutalmazásának hatása a nyáltesztoszteronszintre és a teljesítményre fiatal felnőtt férfiakban: A hiperversengés szerepe

Korábbi kutatások megmutatták, hogy versengő helyzetben a nagyobb jutalom megnövekedett fiziológiai arousallal jár. Mégis kevés tanulmány érintette a jutalmazás hatását a tesztoszteron (T) szintre, annak ellenére, hogy ez a hormon érzékenyen reagál a versengő helyzetekre és státuszváltozásokra. A jelen kutatás versengő helyzetben vizsgálta a nyáltesztoszteron és fiziológiai arousal (szívritmus, szívritmusvariabilitás) változásait fiatal felnőtt férfi mintán (N = 40, átlag életkor = 21.7 ± 2.3 év). A résztvev ők egy videojátékban versengtek egymással, ahol a páros egyik tagja nyert, a másik veszített a képességeknek és erőfeszítésnek megfelelően. A párosok véletlenszerű csoportosítása alapján résztvevők vagy egyenlő pénzjutalmat kaptak, vagy a győztes több jutalmat kapott, mint a vesztes (egyenlőtlen jutalom). A pszichofiziológiai és endokrinológiai méréseken túl a résztvevők versengéssel kapcsolatos attitűdjeit (hiperversengés, önfejlesztő versengés) és a versengő helyzetben mutatott hangulati változásait is felmértük kérdőívek segítségével. Az eredmények azt mutatták, hogy a versengés mindkét csoportban növelte mind a szubjektív, mind a fiziológiai arousalszintjét, ám a jutalom mértéke nem volt szignifikáns hatással a T szintre. A T szint csak a vesztes hiperversengőkben növekedett szignifikánsan. A kompetitív teljesítmény korrelált a győztesek és vesztesek T szintjével, illetve annak változásával, alátámasztva azt a korábbi megfigyelést, hogy a versengő teljesítmény és a T egymást kölcsönösen meghatározó kapcsolatban állnak. A kapott eredmények összefüggésben vannak a státuszinstabilitás-hipotézissel

Oligomannan Prebiotic Attenuates Immunological, Clinical and Behavioral Symptoms in Mouse Model of Inflammatory Bowel Disease

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Isolation of Mycoplasma anserisalpingitidis from swan goose (Anser cygnoides) in China

Abstract Background: Mycoplasma anserisalpingitidis causes significant economic losses in the domestic goose (Anser anser) industry in Europe. As 95% of the global goose production is in China where the primary species is the swan goose (Anser cygnoides), it is crucial to know whether the agent is present in this region of the world. Results: Purulent cloaca and purulent or necrotic phallus inflammation were observed in affected animals which represented 1–2% of a swan goose breeding flock (75,000 animals) near Guanghzou, China, in September 2019. From twelve sampled animals the cloaca swabs of five birds (three male, two female) were demonstrated to be M. anserisalpingitidis positive by PCR and the agent was successfully isolated from the samples of three female geese. Based on whole genome sequence analysis, the examined isolate showed high genetic similarity (84.67%) with the European isolates. The antibiotic susceptibility profiles of two swan goose isolates, determined by microbroth dilution method against 12 antibiotics and an antibiotic combination were also similar to the European domestic goose ones with tylvalosin and tiamulin being the most effective drugs. Conclusions: To the best of our knowledge this is the first description of M. anserisalpingitidis infection in swan goose, thus the study highlights the importance of mycoplasmosis in the goose industry on a global scale. Keywords: Antibiotic, China, Mycoplasma, Swan goose, Phallus inflammation, Venereal disease, Whole genom