Puerarin protects rat brain against ischemia/reperfusion injury by suppressing autophagy via the AMPK-mT OR-ULK1 signaling pathway

Puerarin suppresses autophagy to alleviate cerebral ischemia/reperfusion injury, and accumulating evidence indicates that the AMPKm TOR signaling pathway regulates the activation of the autophagy pathway through the coordinated phosphorylation of ULK1. In this study, we investigated the mechanisms underlying the neuroprotective effect of puerarin and its role in modulating autophagy via the AMPK-m TOR-ULK1 signaling pathway in the rat middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. Rats were intraperitoneally injected with puerarin, 50 or 100 mg/kg, daily for 7 days. Then, 30 minutes after the final administration, rats were subjected to transient middle cerebral artery occlusion for 90 minutes. Then, after 24 hours of reperfusion, the Longa score and infarct volume were evaluated in each group. Autophagosome formation was observed by transmission electron microscopy. LC3, Beclin-1 p62, AMPK, m TOR and ULK1 protein expression levels were examined by immunofluorescence and western blot assay. Puerarin substantially reduced the Longa score and infarct volume, and it lessened autophagosome formation in the hippocampal CA1 area following cerebral ischemia/reperfusion injury in a dose-dependent manner. Pretreatment with puerarin（50 or 100 mg/kg） reduced Beclin-1 expression and the LC3-II/LC3-I ratio, as well as p-AMPK and p S317-ULK1 levels. In comparison, it increased p62 expression. Furthermore, puerarin at 100 mg/kg dramatically increased the levels of p-m TOR and p S757-ULK1 in the hippocampus on the ischemic side. Our findings suggest that puerarin alleviates autophagy by activating the APMK-m TOR-ULK1 signaling pathway. Thus, puerarin might have therapeutic potential for treating cerebral ischemia/reperfusion injury.

Age-hardening behavior and microstructure of Cu-15Ni-8Sn-0.3Nb alloy prepared by powder metallurgy and hot extrusion

Cu-15Ni-8Sn-0.3Nb alloy rods were prepared by means of powder metallurgy followed by hot extrusion.Element maps obtained by electron probe micro analyzer(EPMA)showed that Nb-rich phases were formed and distributed within grains and at grain boundaries of the Cu-15Ni-8Sn-0.3Nb alloy.Transmission electron microscope(TEM)results indicated that there was no obvious orientation relationship between these phases and the matrix.Spinodal decomposition and ordering transformation appeared at early stages of aging at400°C and caused significant strengthening.Cu-15Ni-8Sn-0.3Nb alloy exhibited both higher strength(ultimate tensile strength>1030MPa)and higher tensile ductility(elongation>9.1%)than Cu-15Ni-8Sn alloy after aging treatment.The improvement was caused by Nb-rich phases at grain boundaries which led o the refinement of grain size and postponed the growth of discontinuous precipitates during aging.

Stress increases MHC-I expression in dopaminergic neurons and induces autoimmune activation in Parkinson’s disease

The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation.All animal experiments were approved by the Southern Medical University Ethics Committee(No.81802040,approved on February 25,2018).

Cerebral corridor creator for resection of trigone ventricular tumors:Two case reports

BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge due to its inaccessible location and intricate adjacent relationships with essential structures such as the optic radiation(OR)fibers.New brain retraction systems have been developed to minimize retraction-associated injury.To date,there is little evidence supporting the superiority of any retraction system in preserving the white matter tract integrity.This report illustrates the initial surgical excision in two patients using a new retraction system termed the cerebral corridor creator(CCC)and demonstrates its advantage in protecting OR fibers.CASE SUMMARY We report two patients with nonspecific symptoms,who had trigone ventricular lesions that involved the neighboring OR identified on preoperative diffusion tensor imaging(DTI).Both patients underwent successful surgical excision using the CCC.Total tumor removal was achieved without additional neurological deficit.DTI showed that the OR fibers were preserved along the surgical field.Preoperative symptoms were alleviated immediately after surgery.Clinical outcomes were improved according to the Glasgow-Outcome-Scale and Activity-of-Daily-Living Scale assessments.CONCLUSION In the two cases,the CCC was a safe and useful tool for creating access to the deep trigonal area while preserving the white matter tract integrity.The CCC is thus a promising alternative brain retractor.

Application of Keyhole Microneurosurgery in China

INTRODUCTIONMicroneurosurgery made its debut in the early 1960s. It became popular in the medical field and became a primary operation method in neurosurgery since it improved the efficacy of neurosurgery with a less surgery-related injury. Over the past five decades, the accumulation of experience of microsurgery, improvement of microsurgery techniques, refined micro-instruments, and advanced preoperative diagnostic imaging allowed the evolution of microneurosurgery techniques and further reduced surgery-related trauma.