LGR6 promotes glioblastoma malignancy and chemoresistance by activating the Akt signaling pathway.

Chemoresistance is the primary cause of the poor outcome of glioblastoma multiforme (GBM) therapy. Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) is involved in the growth and proliferation of several types of cancer, including gastric cancer and ovarian cancer. Therefore, the aim of the present study was to investigate the role of LGR6 in GBM malignancy and chemoresistance. Cell counting kit-8 and Matrigel®-Transwell assays were conducted to assess GBM cell viability and invasion. The effect of LGR6 on cell cycle progression and activation of Akt signaling was analyzed by performing propidium iodide staining and western blotting, respectively. The results demonstrated that LGR6, a microRNA-1236-3p target candidate, promoted GBM cell viability and invasion, and mediated temozolomide sensitivity in SHG-44 and U251 GBM cells. In addition, LGR6 triggered the activation of the Akt signaling pathway during GBM progression. Collectively, the results of the present study suggested that LGR6 promoted GBM malignancy and chemoresistance, at least in part, by activating the Akt signaling pathway. The results may aid with the identification of a novel therapeutic target and strategy for GBM.

Blocking cerebral lymphatic drainage deteriorates cerebral oxidative injury in rats with subarachnoid hemorrhage.

Substances and fluid in the brain and subarachnoid spaces may be drained into extracranial lymphatics. This study aimed to investigate the possible role of cerebral lymphatic drainage in the process of cerebral injury following subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, and SAH plus cervical lymphatic blockage (SAH + CLB) groups. Autologous arterial hemolysate was injected into rats' cisterna magna to induce SAH. At time of 24 and 72 h after SAH, the rats were sacrificed for serum lactate dehydrogenase (LDH) activity, brain tissue superoxide dismutase (SOD) activity, and brain tissue malonaldehyde (MDA) content detection. It was found that serum LDH activity increased in rats of SAH group comparing with non-SAH group. SAH also resulted in decreased brain tissue SOD activity and increased brain tissue MDA content. In rats of SAH + CLB group, the increase of serum LDH activity was to a lager extent. Meanwhile, brain tissue SOD activity decreased and MDA content increased to a lager extent, as compared with SAH group. It was concluded that blockage of cerebral lymphatic drainage deteriorates cerebral oxidative injury after SAH, indicating cerebral lymphatic drainage may exert intrinsic protective effects against cerebral injury following SAH.

Intranasal delivery of calcitonin gene-related peptide reduces cerebral vasospasm in rats.

Cerebral vasospasm is the primary cause of sequelae and poor clinical conditions of subarachnoid hemorrhage (SAH); therefore, it is imperative to relieve vasospasm and improve cerebral blood supply. Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is normally released by trigeminal sensory fibers but depleted following SAH. We propose that intranasal application may be an effective way to deliver CGRP to the brain and ameliorate vasospasm after SAH. In this study, we intranasally applied CGRP to rats and induced SAH by double-injection of autologous blood into the cisterna magna. Compared to intravenous injection, intranasal delivery led to a 10-fold higher level of CGRP in the brain. Intranasal CGRP significantly ameliorated vasospasm, improved cerebral blood flow, and reduced cortical and endothelial cell death. Moreover, CGRP increased the levels of vascular endothelial growth factor and stimulated angiogenesis. Altogether, our data demonstrate that intranasal CGRP delivery is a promising method for moderating vasospasm and reducing the associated ischemic brain injury after SAH in rats, and suggest that it may be a potential approach in clinic.