Recombinant human brain natriuretic peptide attenuates ischemic brain injury in mice by inhibiting oxidative stress and cell apoptosis via activation of PI3K/AKT/Nrf2/HO-1 pathway.

Ischemic stroke followed by cerebral artery occlusion is a main cause of chronic disability worldwide. Recombinant human brain natriuretic peptide (rhBNP) has been reported to alleviate sepsis-induced cognitive dysfunction and brain I/R injury. However, the function and molecular mechanisms of rhBNP in ischemic brain injury have not been clarified. For establishment of an animal model of ischemic brain injury, C57BL/6 mice were treated with middle cerebral artery occlusion (MCAO) surgery for 1 h and reperfusion for 24 h. After subcutaneous injection of rhBNP into model mice, neurologic deficits were assessed by evaluating behavior of mice according to Longa scoring system, and TTC staining was utilized to determine the brain infarct size of mice. The levels of oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA), were detected in hippocampal tissues of mice by corresponding kits. Cell apoptosis in hippocampus tissues was examined by TUNEL staining. Protein levels of antioxidant enzymes (HO-1 and NQO1) in cerebral cortex, apoptotic markers (Bax, Bcl-2, and cleaved caspase), and PI3K/AKT pathway-associated factors in hippocampus were tested by western blot analysis. The results revealed that injection of rhBNP decreased neurologic deficit scores, the percent of brain water content, and infarct volume. Additionally, rhBNP downregulated MDA level, upregulated the levels of SOD, CAT, and GSH in hippocampus of mice, and increased protein levels of HO-1 and NQO1 in the cortex. Cell apoptosis in hippocampus tissues of model mice was inhibited by rhBNP which was shown as the reduced TUNEL-positive cells, the decreased Bax, cleaved caspase-3, and cleaved caspase-9 protein levels, and the enhanced Bcl-2 protein level. In addition, rhBNP treatment activated the PI3K/AKT signaling pathway and upregulated the protein levels of HO-1 and NRF2. Overall, rhBNP activates the PI3K/AKT/HO-1/NRF2 pathway to attenuate ischemic brain injury in mice after MCAO by suppression of cell apoptosis and oxidative stress.

Effect of Admission Hyperglycemia on Safety and Efficacy of Intravenous Alteplase Before Thrombectomy in Ischemic Stroke: Post-hoc Analysis of the DIRECT-MT trial.

Hyperglycemia is associated with decreased recanalization probability and increased risk of hemorrhagic complications for stroke patients treated with intravenous alteplase. However, whether hyperglycemia modifies alteplase treatment effect on clinical outcome in patients with large vessel occlusion stroke undergoing endovascular thrombectomy is uncertain. We conducted this study to determine a possible interaction effect between admission hyperglycemia and intravenous alteplase prior to thrombectomy in patients with large vessel occlusion stroke. In this post-hoc analysis of a randomized trial (DIRECT-MT) comparing intravenous alteplase before endovascular treatment vs. endovascular treatment only, 649 with available baseline glucose measurements were included. The treatment-by-admission hyperglycemia (defined as plasma glucose levels ≥ 7.8 mmol/L [140 mg/dL]) interaction was assessed using logistic regression models. As a result, among 649 patients included, 224 (34.5%) were hyperglycemic at admission. There was evidence of alteplase treatment effect modification by hyperglycemia (Pinteraction = 0.025). In patients without hyperglycemia, combination therapy was associated with better outcomes compared to mechanical thrombectomy alone (adjusted common odd ratio [acOR] 1.46, 95% CI [1.04-2.07]), but not in hyperglycemic patients (acOR 0.74, 95% CI [0.46-1.20]). Combination therapy led to an absolute increase of 6% excellent outcome (mRS 0-1) in non-hyperglycemic patients (aOR 1.71, 95% CI [1.05-2.79]), but resulted in a 12.3% absolute decrease (aOR 0.42 [95% CI, 0.19-0.95] in hyperglycemic patients (Pinteraction = 0.003). In conclusion, for large vessel occlusion patients directly presenting to a thrombectomy-capable hospital, hyperglycemia modified combination treatment effect on clinical outcome. Combination therapy was beneficial in patients without hyperglycemia, while thrombectomy alone may be preferred in hyperglycemic patients. Further studies are needed to confirm this result.Trial Registration Information: clinicaltrials.gov Identifier: NCT03469206.

Choriocapillaris Ischemia at the Leakage Point of Patients With Acute Central Serous Chorioretinopathy.

Purpose: We aimed to determine ischemia of the choriocapillaris at the leakage point of patients with acute central serous chorioretinopathy (CSC) by optical coherence tomographic angiography (OCTA). Methods: A retrospective study of 38 eyes of 38 acute CSC patients with spontaneous complete resolution of subretinal fluid (SRF) was conducted and patients were followed for 3 months. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed at baseline. Best corrected visual acuity (BCVA) and OCTA were collected at baseline and at follow-up visits. An age- and refractive error-matched control group consisted of 40 eyes of 40 healthy people. Results: The BCVA of patients significantly improved at 1 and 3 months. At baseline, all eyes showed a decreased choriocapillaris vessel density. The mean vessel density of superficial choroid (VDSC) at the leakage point area was 44.18 ± 9.27, which increased to 54.31 ± 9.70 at 1 month (p < 0.001) and to 55.19 ± 6.46 at 3 months (p < 0.001). The mean vessel density ratio was 0.90 ± 0.16 at baseline, which increased to 0.96 ± 0.15 at 1 month (p = 0.037) and to 0.97 ± 0.08 at 3 months (p = 0.016). The highest VDSC of patients was lower than that of normal control (p < 0.001). Conclusions: The VDSC at the leakage point of acute CSC patients was significantly thinner and regularly increased with the recovery process, which suggested that ischemia might be one of the initiating factors in the pathogenesis of acute CSC.

To evaluate the microcirculation of retinochoroid capillary between acute and chronic central serous chorioretinopathy with OCTA.

ABSTRACT: To investigate the difference in chorioretinal microcirculation between acute central serous chorioretinopathy (aCSC) and chronic central serous chorioretinopathy (cCSC) using optical coherence tomography angiography.In total, 65 patients previously diagnosed with central serous chorioretinopathy (33 aCSC and 32 cCSC) were included in our cross-sectional study. All patients underwent complete ophthalmologic assessment including logarithm of the minimum angle of resolution best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography angiography. Sixty eyes of 60 refractive error and age matched healthy people were selected as control.The vessel density of inner retina in patients with aCSC were higher than that in patients with cCSC (51.32 ±â€Š2.01 vs 49.15 ±â€Š3.68, P = .004), however, the vessel density of superficial choroid layer in aCSC were significantly lower than that in cCSC (49.83 ±â€Š6.96 vs 53.42 ±â€Š6.28, P = .033). Further analysis of the data reveals the presence of a distinct choroidal neovascularization (CNV) in 8 patients (25%) with cCSC while there was no evidence of CNV in patients with aCSC.Our study can contribute to a better understanding of the difference in retinochoroid microcirculation between aCSC and cCSC. The vessel density of inner retina was lower and the vessel density of superficial choroid was higher in cCSC, and patients with cCSC were more susceptible to CNV than patients with aCSC.

[Trabeculectomy combined amniotic membrane transplantation for refractory glaucoma].

PURPOSE: To evaluate the clinical effect of trabeculectomy combined amniotic membrane transplantation in refractory glaucoma. METHODS: Seventeen eyes of sixteen patients with uncontrolled glaucoma underwent trabeculectomy combined amniotic membrane transplantation. The mean follow-up was 11.2 months (3-24 months). RESULTS: The mean preoperative intraocular pressure (IOP) was (39.72 +/- 7.26) mmHg which decreased to a mean postoperative IOP of (14.62 +/- 3.72) mmHg (P < 0.001). There was an obvious diffusion blebs in each eye 3 months after the operation, there were functional blebs in 16 eyes 6 months after the operation, there were functional blebs in 14 eyes. The anterior chamber reaction was mild. CONCLUSIONS: Trabeculectomy combined amniotic membrane transplantation is a safe and effective method for refractory glaucoma.