A scoring system to discriminate blood blister-like aneurysms: a multidimensional study using patient-specific model.

Presurgical discrimination of blood blister-like aneurysms (BBAs) can assist neurosurgeons in clinical decision-making. The aim of this study was to investigate the characteristics of BBAs and construct a useful tool to distinguish BBAs. This study reviewed patients with small/median, hemispherical, and wide-necked aneurysms of the internal carotid artery in our institution. BBAs were identified via their intraoperative findings. A hemodynamic analysis was performed using a patient-specific model. The independent risk factors of BBAs were investigated using a logistic analysis. A scoring system was then established to discriminate BBAs, in which its predicting value was analyzed using receiver operating characteristic (ROC) analysis. A total of 67 aneurysms comprising 21 BBAs were enrolled. Comparing features between BBAs and non-BBAs, statistical significances were found in the aspect ratio (AR), height-to-width ratio, aneurysm angle (AA), wall shear stress gradient (WSSG), and normalized wall shear stress average. A multivariate logistic analysis identified AR (OR = 0.29, p = 0.021), WSSG (OR = 1.54, p = 0.017) and AA (OR = 2.49, p = 0.039) as independent risk factors for BBAs. A scoring system was constructed using these parameters, effectively distinguishing BBAs (AUC = 0.931, p < 0.01). Our multidimensional scoring system may effectively assist in the discrimination of BBAs from wide-necked non-BBAs.

GLP-1R Agonist Liraglutide Attenuates Inflammatory Reaction and Neuronal Apoptosis and Reduces Early Brain Injury After Subarachnoid Hemorrhage in Rats.

Liraglutide, one of the glucagon-like peptide 1 receptor (GLP-1R) agonists, has been demonstrated to protect brain damage produced by ischemic stroke. However, it remains unknown whether liraglutide attenuates early brain injury after subarachnoid hemorrhage. The present study was performed to explore the effect of liraglutide on early brain injury after subarachnoid hemorrhage in rats, and further investigate the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation, then received subcutaneous injection with liraglutide (50 or 100 µg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, and Evans Blue extravasation were measured 24 h after SAH. Immunofluorescent staining was performed to detect the extent of microglial activation in rat brain 24 h after SAH. TUNEL staining was performed to evaluate neuronal apoptosis in rat brain of SAH. Expression of GLP-1R, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Bcl-2, Bax, and cleaved caspase-3 in rat brain were determined by western blot. Expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in rat brain was assessed by ELISA. Neurological dysfunction, brain water content, Evans Blue extravasation, microglial activation, and neuronal apoptosis were significantly reduced by GLP-1R agonist liraglutide. Expression of GLP-1R in rat brain was decreased after SAH, which is significantly elevated by liraglutide. Expression of inflammatory mediates like COX-2, iNOS, TNF-α, and IL-1ß was increased after SAH, which were significantly inhibited by liraglutide. Furthermore, SAH caused the elevated expression of pro-apoptotic factors Bax and cleaved caspase-3 in rat brain, both of which were inhibited by liraglutide. In addition, liraglutide reversed the expression of anti-apoptotic protein Bcl-2. Our results demonstrated that liraglutide reduces early brain injury and attenuates inflammatory reaction and neuronal apoptosis in rats of SAH. Liraglutide provides neuroprotection against SAH, which might be associated with the inhibition of inflammation and apoptosis.

Anticonvulsive effects of protodioscin against pilocarpine-induced epilepsy.

Epilepsy is associated with increased morbidity and mortality together and places a large financial burden on individuals and society. To evaluate the anticonvulsant action of protodioscin (PDSN) in experiments with animals with pilocarpine-induced convulsions. We assessed the activity of PDSN in pilocarpine induced seizures in combination with different agents which are acting via diverse receptors, such as atropine, memantine, nimodipine, diazepam, and flumazenil, to determine the exact receptors responsible for the action of PDSN. Furthermore, the level of antioxidant markers was investigated in the cerebellum and cerebral cortex in mice to define the antioxidant action of PDSN. The effects of PDSN on proapoptotic markers (i.e., Bcl-2, Bax, and caspase-3) was investigated via western blot analysis. PDSN significantly enhanced latency to the first convulsion and survival compared to the group treated with pilocarpine alone. Moreover, PDSN improved animal survival, and subjects experiencing no convulsions. Striatal glutamate and aspartate levels were not modified, and gamma amino butyric acid (GABA) levels increased, as a result of treatment with PDSN. The results suggest that the anticonvulsive action of PDSN is dependent on inhibitory amino acids. PDSN treatment also significantly decreased nitrite levels in the blood and brain cortex compared to the normal control. In the western blot analysis, PDSN exerted its neuroprotective effect via the upregulation of Bcl-2 and downregulation of Bax and caspase-3. The results of this study suggest that PDSN exerts neuroprotective effects via multiple mechanisms.

miR-204 suppresses the development and progression of human glioblastoma by targeting ATF2.

In human cancers, miRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed, and their alterations contribute to multiple cancer development and progression. Till now, little has been known about the role of miR-204 in human glioblastoma (GBM). In the present study, we used in-vitro assays to investigate the mechanisms of miR-204 in GBM cell lines and 60 cases of GBM tissues. Here, we found that miR-204 expression is downregulated in both GBM cell lines A172, U87 and U251 cells and GBM tissues as compared with NHA cells and normal tissues (all p<0.001). In addition, the ectopic expression of miR-204 suppressed A172 and U87 cell proliferation, migration and invasion. Meanwhile, miR-204 over-expression extremely inhibited the protein expression of ATF2. Notably, the enforced expression of ATF2 in A172 and U87 cells with the over-expression of miR-204 attenuated the inhibitory effects of miR-204 on proliferation, migration and invasion. In conclusion, our findings suggest that miR-204 suppressed cell proliferation, migration and invasion through inhibition of ATF2, thus, miR-204 may function as a useful drug target in the treatment and diagnosis of GBM.