Endogenous FGF21 attenuates blood-brain barrier disruption in penumbra after delayed recanalization in MCAO rats through FGFR1/PI3K/Akt pathway / 中南大学学报(医学版)

OBJECTIVES@#Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO).@*METHODS@#Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting.@*RESULTS@#The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO.@*CONCLUSIONS@#Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.

Changes of reni-angiotensin system and β2-microglobulin during lanaroscopic gynecology surgery under eoudyrak abesthesia / 临床麻醉学杂志

ObjectiveTo investigate the changes of renin-angiotensin-aldosterone system (RAAS) and glomerular filtration rate (GFR) in epidurally-anesthetized patients undergoing gynecological laparoscopy with 15° head-down position and low insufflation pressure. MethodsTwenty gynecological patients(ASA grade I- Ⅱ )were studied during CO2 insufflation with an intra-abdominal pressure of 1012mmHg and 15° head-down position. Arterial blood samples were obtained for the measurements of serum concentrations of plasma renin activity(PRA), angiotensin Ⅱ (All), aldosterone(ALD) and β2-microglobulin(β2-MG)by radioimmunoassay at the following five time points: before insufflation, at 10min, 30min and 60 min after insufflation respectively and after desufflation. Arterial blood gas analysis was made in 10 of the cases simultaneously. ResultsCompared with preinsufflation, there was no significant decrease in the plasma levels of PRA, All ,ALD and β2-MG during CO2 pneumoperitoneum except for PRA at 10 min after insufflation(P ＜0.05). As the time of insufflation went on, the measurements above showed a tendency of slightly increase. The PaCO2 during peritoneal CO2 insufflation was increeseing ( P ＞ 0.05) and reached its maximum at 30 min after insufflation. The pH values of 30～60 min after insufflation were significantly decreased as compared with that of before insufflation. ConclusionThe epidural anesthesia may inhibit the response of RAAS to (CO2 insufflation pressure of 10-12mmHg and has no effect on GFR during gynecological laParoscopy.