Risultati per: GUT

Stroke, Volume 53, Issue Suppl_1, Page AWP242-AWP242, February 1, 2022. Background:Clinically, ~65% of stroke patients are left with functional impairments after stroke and 15% die shortly after their stroke. Increasing evidence suggests that peripheral inflammatory responses after stroke play an important role in determining neurological outcome. Mast cells (MCs) are one of the most rapid responders to injury. MCs release histamine (HA), a pro-inflammatory transmitter that enhances inflammation. Gut MCs are a major source of HA.Hypothesis:We hypothesize that aged animals stroke will lead to robust gut mucosal MC-activation and HA release, with subsequent gut disruption and inflammation. Stabilizing peripheral MCs will decrease peripheral/central inflammation, MC trafficking, and improve stroke outcomes.Methods:We used a reversible middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18mo) wild-type male mice to investigate the MC role in neuroinflammation post-stroke (PS). We stroke the aged animals and treated the animals with 25 mg/kg BW of cromolyn (MC stabilizer), oral gavage. Cromolyn was administered at 3-h, 10-h, 24-h and every other day PS. Positive control group that were stroked but treated only with saline. In total, four groups stroke and sham (surgery control), out of these animals one set received cromolyn and one set received saline. We sacrificed animals at 3-h, 24 –h and 3-days after cromolyn treatment post-stroke.Results:We found that cromolyn administration significantly reduced MC numbers in the brain at 24-hours (P

Stroke, Volume 53, Issue Suppl_1, Page AWP243-AWP243, February 1, 2022. Background:Our previous studies have shown that reproductively senescent (RS) female rats, who have lower circulating levels of the peptide hormone Insulin-like Growth Factor (IGF-1), display worse outcomes after a stroke event than young adult female rats. ICV administration of IGF-1, decreases infarct volume, improves sensory motor performance, and reduces cytokine levels in the ischemic hemisphere of RS females as compared to vehicle-treated controls. Yet, icv IGF1 administration failed to attenuate peripheral inflammation cognitive decline and depressive behaviors in the chronic phase of stroke. In view of the evidence that stroke induces gut dysbiosis, and that gut dysfunction is implicated in depressive and cognitive behaviors, we hypothesize that, unlike icv administration of IGF-1, which is restricted to the brain, systemic i.p. administration of IGF1 would repair the gut, attenuate peripheral cytokine levels and improve long-term behavior outcomes.Methods:Acyclic middle-aged Sprague Dawley female rats (9-11 mos) were subjected to endothelin-1 induced middle cerebral artery occlusion (MCAo) or sham operation. Animals received IGF1 via i.p. injections 4h post MCAo and 24 h post MCAo, or icv infusions, while controls received vehicle. Sensory motor tests, blood and gut samples were acquired pre and post MCAo. Animals were terminated either in the acute phase (2d) or chronic phase (20d). The latter group was also subject to tests of cognition and depressive-like behavior.Results:In contrast to icv treatment, i.p.-IGF-1 did not reduce infarct volume or acute sensory motor impairment but significantly attenuated circulating levels of TNFα and IL12p70. In addition, ip-IGF-1 significantly attenuated post stroke gut dysmorphology, by preserving villus:crypt ratio and expression of tight junction proteins ZO1 and claudin-2. In addition, i.p. IGF1 treatment attenuated the reduction of social interaction and novel object preference post MCAo.Conclusion:Since long term disability after stroke is correlated with elevated levels of peripheral cytokines, our data suggest that systemic IGF1 may be a better therapeutic option for long term cognitive and depressive behaviors after stroke.

Stroke, Ahead of Print. Background and Purpose:Environmental factors are important with respect to the rupture of cerebral aneurysms. However, the relationship between the gut microbiome, an environmental factor, and aneurysm rupture is unclear. Therefore, we compared the gut microbiome in patients with unruptured intracranial aneurysms (UIAs) and ruptured aneurysms (RAs) to identify the specific bacteria causing the rupture of cerebral aneurysms.Methods:A multicenter, prospective case-control study was conducted over one year from 2019 to 2020. The fecal samples of patients with stable UIAs and RAs immediately after onset were collected. Their gut microbiomes were analyzed using 16S rRNA sequencing. Subsequently, a phylogenetic tree was constructed, and polymerase chain reaction was performed to identify the specific species.Results:A total of 28 RAs and 33 UIAs were included in this study. There was no difference in patient characteristics between RAs and UIAs: age, sex, hypertension, dyslipidemia, diabetes status, body mass index, and smoking. No difference was observed in alpha diversity; however, beta diversity was significantly different in the unweighted UniFrac distances. At the phylum level, the relative abundance ofCampylobacterin the RA group was larger than that in the UIA group. Furthermore, the gut microbiome in the RA and UIA groups exhibited significantly different taxonomies. However,Campylobacterwas focused on because it is widely known as pathogenic among these bacteria. Then, a phylogenetic tree of operational taxonomic units related toCampylobacterwas constructed and 4 species were identified. Polymerase chain reaction for these species identified that the abundance of the genusCampylobacterandCampylobacter ureolyticuswas significantly higher in the RA group.Conclusions:The gut microbiome profile of patients with stable UIAs and RAs were significantly different. The genusCampylobacterandCampylobacter ureolyticusmay be associated with the rupture of cerebral aneurysms.