Ping Luan

Edaravone Protects HT22 Neurons from H2O2-induced Apoptosis by Inhibiting the MAPK Signaling Pathway

Oxidative stress is frequently implicated in the pathology of neurodegenerative diseases. This study aimed to investigate the effects and their underlying mechanism(s) of edaravone upon hydrogen peroxide (H2O2)–induced oxidative stress and apoptosis in HT22 cells, a murine hippocampal neuronal model.

PI3K/AKT/mTOR/p70S6K Pathway Is Involved in Aβ25-35-Induced Autophagy

Disruption or deregulation of the autophagy system has been implicated in neurodegenerative disorders such as Alzheimers disease (AD). Aβ plays an important role in this autophagic system. In many cases, autophagy is regulated by the phosphatidylinositol 3-phosphate kinase/AKT/mammalian target of rapamycin/p70 ribosomal protein S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway. However, whether this signaling pathway is involved in Aβ-induced autophagy in neuronal cells is not known. Here, we studied whether Aβ25-35 induces autophagy in HT22 cells and C57 mice and investigated whether PI3K is involved in the autophagy induction. We found that Aβ25-35 inhibited HT22 cell viability in a dose- and time-dependent manner. Aβ25-35 induced autophagosome formation, the conversion of microtubule-associated protein light chain 3 (LC3), and the suppression of the mTOR pathway both in vitro and in vivo. Furthermore, Aβ25-35 impaired the learning abilities of C57 mice. Our study suggests that Aβ25-35 induces autophagy and the PI3K/AKT/mTOR/p70S6K pathway is involved in the process, which improves our understanding of the pathogenesis of AD and provides an additional model for AD research.

Increasing the Permeability of the Blood-brain Barrier in Three Different Models in vivo.

Blood–brain barrier (BBB) plays significant roles in the circumstance maintains for the central nervous system (CNS). The dysfunction of the BBB could occur in all pathological conditions of CNS diseases, such as ischemic stroke, cerebral edema, or inflammatory disorders. However, the comparisons among different animal models with a broken BBB in vivo are still need to be further studied.

Kallikrein Gene Transfer Induces Angiogenesis and Further Improves Regional Cerebral Blood Flow in the Early Period After Cerebral Ischemia/Reperfusion in Rats

SUMMARY  Aims: The aims of this study were to find out whether kallikrein could induce angiogenesis and affect the cerebral blood flow (rCBF) in the early period after cerebral ischemia/reperfusion (CI/R). Methods: The adenovirus carried human tissue kallikrein (HTK) gene was administrated into the periinfarction region after CI/R. At 12, 24, and 72 h after treatments, neurological deficits were evaluated; expression of HTK and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry staining; the infarction volume was measured; and rCBF was examined by 14C‐iodoantipyrine microtracing technique. Results: The expression of VEGF was enhanced significantly in pAdCMV‐HTK group than controls over all time points (P < 0.05). Furthermore, the rCBF in pAdCMV‐HTK group increased markedly than controls at 24 and 72 h after treatment (P < 0.05), and the improved neurological deficit was accompanied by reduced infarction volume in pAdCMV‐HTK group 24 and 72 h posttreatment. Conclusion: In the early period after CI/R, kallikrein could induce the angiogenesis and improve rCBF in periinfarction region, and further reduce the infarction volume and improve the neurological deficits.

Basic Fibroblast Growth Factor Protects C17.2 Cells from Radiation-Induced Injury through ERK1/2

To establish a radiation‐induced neural injury model using C17.2 neural stem cells (NSCs) and to investigate whether basic fibroblast growth factor (bFGF) can protect the radiation‐induced injury of C17.2 NSCs. Furthermore, we aim to identify the possible mechanisms involved in this model.

Neurotropin® alleviates hippocampal neuron damage through a HIF-1α/MAPK pathway

The main purpose was to verify the potent capacity of Neurotropin® against neuronal damage in hippocampus and to explore its underlying mechanisms.

Effect of Edaravone on Aβ1–40 Induced Enhancement of Voltage‐Gated Calcium Channel Current

Correspondence Dr. Jun Liu, Department of Neurodegenerative Diseases and Aging, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong 510120, China. Tel.: 86-20-81332621; Fax: 86-20-81332620; E-mail: docliujun@hotmail.com Dr. Ping Luan, Medical School, Shenzhen University, Shenzhen, Guangdong 518060, China. Tel.: 86-755-26958869; Fax: 86-755-86671906; E-mail: Luanping@mail.com Received 13 November 2011; accepted 14 November 2011

Applications of fluorescence lifetime imaging in clinical medicine

Fluorescence lifetime is not only associated with the molecular structure of fluorophores, but also strongly depends on the environment around them, which allows fluorescence lifetime imaging microscopy (FLIM) to be used as a tool for precise measurement of the cell or tissue microenvironment. This review introduces the basic principle of fluorescence lifetime imaging technology and its application in clinical medicine, including research and diagnosis of diseases in skin, brain, eyes, mouth, bone, blood vessels and cavity organs, and drug evaluation. As a noninvasive, nontoxic and nonionizing radiation technique, FLIM demonstrates excellent performance with high sensitivity and specificity, which allows to determine precise position of the lesion and, thus, has good potential for application in biomedical research and clinical diagnosis.

Inhibitory Effect of Bcl-xL Gene on Toxicity Induced by Sodium Nitroprusside in SH-SY5Y cells

Nitric oxide (NO) at physiological concentration is an intracellular messenger molecule in central nervous system (CNS). It plays a pivotal role in maintaining normal physiological function. While excessive NO produced by inducible NO synthase may lead to a variety of neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and cerebral vascular disease, and so on [1,2]. It has been demonstrated that neural damage triggered by NO donor sodium nitroprusside

The effect of V-ATPase function defects in pathogenesis of Alzheimer's disease

Alzheimer’s disease (AD) is a neurological degenerative disease characterized by a decrease in cognitive function and associated with a decline in life function and abnormal mental behavior.1 The aggregation of Aβ in brain parenchyma is the pathogenic factor and key link of AD.2 Aβ degradation has been gradually proven to be dependent on the degradation function of the small glial cell lysosomes in brain.3 The aggregation of Aβ in brain involves the rate balance between the generating and eliminating Aβ.4 As the finaldegradation organelles of Aβ, lysosomes are the most important organelles of the Aβ degradation.5 The activity of protease in intracellular lysosomes is mainly determined by the pH value in lysosomes.6 To maintain the pH value in a variety of important organelles is inseparable from the vacuolartype H+ATPase (VATPase), which belongs to the family of the ATP dependent proton pump. And, we have already known that bafilomycin A1 (Baf A1) is a protonpump inhibitor which can inhibit the VATPase transporting H+ form cytoplasm to lysosomes. The pH value will increase when the H+ cannot be transported into lysosomes. The Aβ degradation would be negatively influenced by the acid environment changed in lysosomes. Accordingly, the Aβ aggradation aggravates. Segregate and culture the primary microglia from TgAPPsw (Tg2576) mice and wild mice brain.7 Because the fluorescence intensity of pHsensitive fluorescein reduces with the pH value, the pH assessment of cytoplasm and lysosome is based on the fluorescence ratio of pHsensitive fluorescein to pHinsensitive rose essence. According to this principle, we detect the differences in intracellular pH value and lysosome pH value between the TgAPPsw (Tg2576) mice and wild mice. We observe the fluorescence intensity of these fluoresceins by confocal microscope and calculate fluorescence intensity ratio of pHsensitive fluorescein to pHinsensitive rose essence. According to the ratio, we get the pH value of cytoplasm and lysosom. Then, we find out the functional variation of the VATPase. HT22 cells are divided into control group, no serum culture group, Aβ processing group, and Aβ+Bafilomycin A1 group. Stimulate the HT22 cells with 40 μmol/L and 10 μmol/L of Aβ2535, then measure the changes of cell viability, WBC spots, LC3, and VATPase protein.