Browsing by Author "Yang, Shao-Hua"
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Item Artemisinin Protects Oxidative Stress-induced Neuronal Apoptosis Via Up-Regulation of Akt/Bcl-2 Signaling(2017-03-14) Liu, Ran; Xie, Luokun; Li, Wenjun; Winters, Ali; Chaudhari, Kiran; Prah, Jude; Yang, Shao-Hua; Lin, Shao-PengPurpose: Artemisinin is a powerful anti-malarial drug that has been in use for decades. Recently, the novel biological effects of artemisinin on cancer, inflammation-related disorders, and cardiovascular disease were reported. The aim of this study was to explore the neuroprotective actions of artemisinin. Methods: The model of glutamate-induced oxidative injury in HT22 hippocampal cells was established to simulate cellular ischemic model. We investigated the effect of artemisinin on oxidative stress-induced cell apoptosis death and the activity of Akt/Bcl-2 pathway in HT22 cells. Results: Pretreatment with artemisinin attenuated reactive oxygen species (ROS) generations, preventing the decline of mitochondrial membrane potential and rescued the HT22 cells form glutamate-induced apoptosis death. The Akt/Bcl-2 pathway was activated by artemisinin in time dependent manner. Furthermore, the artemisinin inhibitor MK2206 blocked the neuroprotective effect of artemisinin. Conclusions: Artemisinin protects neuronal HT22 cell from glutamate-induced oxidative injury and apoptosis via Akt/Bcl-signaling, thereby might be applicated for clinical neurological therapy.Item Cholesterol sulfate alters astrocyte metabolism and offers some neuroprotective effects(2018-03-14) Yang, Shao-Hua; Prah, JudeIntroduction: Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and Dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as endogenous regulator of cholesterol synthesis. It is known that CS serves as a substrate for synthesizing other sterol sulfates in the brain. However, the role of CS in neurological insult and brain metabolism is unknown. Our goal in this study is to investigate the neuroprotective action of CS as well as its effect on brain energy metabolism. Materials and Methods: Primary astrocytes were prepared from the cortex of postnatal day 0-2 C57BL/6 pups and seeded in Dulbecco’s modified eagle medium (DMEM) with 10% FBS under normal glucose (5.5 mM). HT-22 cells were maintained in high glucose (25 mM) DMEM supplemented with charcoal stripped FBS. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte and HT-22 cells using Calcien AM cell viability assay, flow cytometry, seahorse extracellular flux analysis, and metabolism assay kits. Results: CS protects HT22 cells against glutamate toxicity and impact astrocyte metabolism by increasing ATP, and glycogen contents. Conclusion: Our study demonstrated that CS have neuroprotective effect and modulate brain energy metabolism. Further studies are needed to determine the mechanisms underlying the neuroprotective action of CS and its action on brain energy metabolism.Item Experimental ischemic stroke induces secondary white matter degeneration and long-term cognitive impairment(2024-03-21) Berry, Raymond; Liu, Ran; Winters, Ali; Spann, Clair; Ampofo, Hannah; Colon-Perez, Luis; Sumien, Nathalie; Yang, Shao-HuaClinical investigations have detected extensive white matter degeneration in individuals affected by ischemic stroke. Nonetheless, current stroke research has primarily concentrated on the infarct and periinfarct penumbra regions. The exploration of white matter degeneration's role after ischemic stroke and its contribution to post-stroke cognitive impairment and dementia (PSCID) has been limited in experimental models. Understanding the impact of white matter degeneration on PSCID in these models could offer valuable insights into potential therapeutic targets and interventions for alleviating cognitive decline following ischemic stroke. In this study, we analyzed the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairment persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4-month after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) revealed white matter hyperintensities in the corpus callosum and fornix across bilateral hemispheres. A positive association between the volume of white matter hyperintensities and total cerebroventricular volume was noted in stroke rats. Further evidence of bilateral white matter degeneration was indicated by the reduction of fractional anisotropy (FA) and quantitative anisotropy (QA) in diffusion-weighted MRI (DWI) analysis. FA measures water diffusion directionality; reduced FA implies decreased white matter tract coherence. QA, linked to diffusion directionality, indicates microstructural white matter changes with decreased QA. Reduced FA and QA in DWI MRI suggest brain microstructural integrity changes, involving myelin sheath disruption, axonal damage, or overall white matter deterioration. Additionally, microglia and astrocyte activation were identified in the bilateral corpus callosum after stroke. This inflammatory response indicates the involvement of glial cells in the post-stroke environment, suggesting a complex interplay between structural alterations and neuroinflammatory processes that may contribute to the observed changes in white matter integrity. Understanding these multifaceted mechanisms is crucial for developing targeted interventions aimed at promoting recovery and minimizing long-term neurological consequences following ischemic stroke. The importance of these results is underscored by their potential connection to neurological or neurodegenerative conditions, given that white matter degeneration is commonly noted in diverse neurological disorders, including Alzheimer's disease, multiple sclerosis, and other related conditions. Our study suggests that experimental ischemic stroke induced by MCAO in young rats replicates long-term cognitive impairment and pervasive white matter degeneration observed in ischemic stroke patients. This model provides an invaluable tool for unraveling the mechanisms underlying post-stroke secondary white matter degeneration and its contribution to PSCID. Researchers and clinicians use these metrics to understand and monitor the progression of neurological diseases, potentially aiding in early diagnosis and treatment planning. This research may pave the way for a more comprehensive understanding of the mechanisms underlying post-stroke cognitive impairment and dementia, ultimately leading to improved strategies for patient care and rehabilitation.