Cyclosporine A Protects Retinal Explants against Hypoxia

The retina is a complex neurological tissue and is extremely sensitive to an insufficient supply of oxygen. Hypoxia plays a major role in several retinal diseases, and often results in the loss of cells that are essential for vision. Cyclosporine A (CsA) is a widely used immunosuppressive drug. Furthermore, treatment with CsA has neuroprotective effects in several neurologic disorders. No data are currently available on the tolerated concentration of CsA when applied to the retina. To reveal the most effective dose, retinal explants from rat eyes were exposed to different CsA concentrations (1–9 µg/mL). Immunohistochemistry with brain-specific homeobox/POU domain protein 3a (Brn3a) and TUNEL staining was performed to determine the percentage of total and apoptotic retinal ganglion cells (RGCs), as well as the responses of micro- and macroglial cells. Furthermore, optical coherence tomography (OCT) scans were performed to measure the changes in retinal thickness, and recordings with multielectrode array (MEA) were performed to evaluate spontaneous RGC spiking. To examine the neuroprotective effects, retinas were subjected to a hypoxic insult by placing them in a nitrogen-streamed hypoxic chamber prior to CsA treatment. In the biocompatibility tests, the different CsA concentrations had no negative effect on RGCs and microglia. Neuroprotective effects after a hypoxic insult on RGCs was demonstrated at a concentration of 9 µg/mL CsA. CsA counteracted the hypoxia-induced loss of RGCs, reduced the percentage of TUNEL+ RGCs, and prevented a decrease in retinal thickness. Taken together, the results of this study suggest that CsA can effectively protect RGCs from hypoxia, and the administered concentrations were well tolerated. Further in vivo studies are needed to determine whether local CsA treatment may be a suitable option for hypoxic retinal diseases.

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The Anti-tumor Activity and Mechanisms of rLj-RGD3 on Human Laryngeal Squamous Carcinoma Hep2 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666191022160024 ◽

2020 ◽

Vol 19 (17) ◽

pp. 2108-2119

Author(s):

Yang Jin ◽

Li Lv ◽

Shu-Xiang Ning ◽

Ji-Hong Wang ◽

Rong Xiao

Keyword(s):

Wound Healing ◽

Western Blot ◽

Morphological Changes ◽

In Vivo Studies ◽

Migration And Invasion ◽

Tunel Staining ◽

Dna Ladder ◽

Western Blot Assay

Background: Laryngeal Squamous Cell Carcinoma (LSCC) is a malignant epithelial tumor with poor prognosis and its incidence rate increased recently. rLj-RGD3, a recombinant protein cloned from the buccal gland of Lampetra japonica, contains three RGD motifs that could bind to integrins on the tumor cells. Methods: MTT assay was used to detect the inhibitory rate of viability. Giemsa’s staining assay was used to observe the morphological changes of cells. Hoechst 33258 and TUNEL staining assay, DNA ladder assay were used to examine the apoptotic. Western blot assay was applied to detect the change of the integrin signal pathway. Wound-healing assay, migration, and invasion assay were used to detect the mobility of Hep2 cells. H&E staining assay was used to show the arrangement of the Hep2 cells in the solid tumor tissues. Results: In the present study, rLj-RGD3 was shown to inhibit the viability of LSCC Hep2 cells in vitro by inducing apoptosis with an IC50 of 1.23µM. Western blot showed that the apoptosis of Hep2 cells induced by rLj- RGD3 was dependent on the integrin-FAK-Akt pathway. Wound healing, transwells, and western blot assays in vitro showed that rLj-RGD3 suppressed the migration and invasion of Hep2 cells by integrin-FAKpaxillin/ PLC pathway which could also affect the cytoskeleton arrangement in Hep2 cells. In in vivo studies, rLj-RGD3 inhibited the growth, tumor volume, and weight, as well as disturbed the tissue structure of the solid tumors in xenograft models of BALB/c nude mice without reducing their body weights. Conclusion: hese results suggested that rLj-RGD3 is an effective and safe suppressor on the growth and metastasis of LSCC Hep2 cells from both in vitro and in vivo experiments. rLj-RGD3 might be expected to become a novel anti-tumor drug to treat LSCC patients in the near future.

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Panton-Valentine Leucocidin Proves Direct Neuronal Targeting and Its Early Neuronal and Glial Impacts a Rabbit Retinal Explant Model

Toxins ◽

10.3390/toxins10110455 ◽

2018 ◽

Vol 10 (11) ◽

pp. 455 ◽

Cited By ~ 2

Author(s):

XuanLi Liu ◽

Michel J Roux ◽

Serge Picaud ◽

Daniel Keller ◽

Arnaud Sauer ◽

...

Keyword(s):

Cell Activation ◽

Ganglion Cells ◽

Glial Activation ◽

Inflammatory Factors ◽

In Vivo Model ◽

Suitable Model ◽

Dependent Manner ◽

Retinal Explants ◽

Glial Changes

: Panton-Valentine leukocidin (PVL) retinal intoxication induces glial activation and inflammatory response via the interaction with retinal neurons. In this study, rabbit retinal explant was used as a model to study neuronal and glial consequences of PVL intoxication. Retinal explants were treated with different concentrations of PVL. PVL location and neuronal and glial changes were examined using immunohistochemistry. Some inflammatory factors were quantified using RT-qPCR at 4 and 8 h. These results were compared with those of control explants. PVL co-localized rapidly with retinal ganglion cells and with horizontal cells. PVL induced Müller and microglial cell activation. Retinal structure was altered and some amacrine and microglial cells underwent apoptosis. Glial activation and cell apoptosis increased in a PVL concentration- and time-dependent manner. IL-6 and IL-8 expression increased in PVL-treated explants but less than in control explants, which may indicate that other factors were responsible for glial activation and retinal apoptosis. On retinal explants, PVL co-localized with neuronal cells and induced glial activation together with microglial apoptosis, which confirms previous results observed in in vivo model. Rabbit retinal explant seems to be suitable model to further study the process of PVL leading to glial activation and retinal cells apoptosis.

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Neuroprotective effects of bergenin in Alzheimer’s disease: Investigation through molecular docking, in vitro and in vivo studies

Behavioural Brain Research ◽

10.1016/j.bbr.2018.08.010 ◽

2019 ◽

Vol 356 ◽

pp. 18-40 ◽

Cited By ~ 21

Author(s):

Priyal Barai ◽

Nisith Raval ◽

Sanjeev Acharya ◽

Ankit Borisa ◽

Hardik Bhatt ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

In Vivo Studies ◽

Neuroprotective Effects

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Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

Molecules ◽

10.3390/molecules25225391 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5391

Author(s):

Zheng Liu ◽

Ming Bian ◽

Qian-Qian Ma ◽

Zhuo Zhang ◽

Huan-Huan Du ◽

...

Keyword(s):

Pc12 Cells ◽

Glycogen Synthase ◽

B Cell Lymphoma ◽

Nuclear Factor Κb ◽

In Vivo Studies ◽

Neuroprotective Effects ◽

Β Amyloid ◽

Gsk 3Β

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.

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The anemia of the newborn induces erythropoietin expression in the developing mouse retina

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00108.2010 ◽

2010 ◽

Vol 299 (1) ◽

pp. R111-R118 ◽

Cited By ~ 5

Author(s):

N. Scheerer ◽

N. Dünker ◽

S. Imagawa ◽

M. Yamamoto ◽

N. Suzuki ◽

...

Keyword(s):

Transforming Growth Factor ◽

Fluorescent Protein ◽

Ganglion Cells ◽

Retinal Development ◽

Transforming Growth Factor Β ◽

Neuroprotective Activity ◽

Mouse Retina ◽

Mrna Levels ◽

Neuroprotective Effects

The hematopoietic hormone erythropoietin (Epo), regularly produced by the kidneys and the liver, is also expressed in neuronal tissue, where it has been found to mediate paracrine neuroprotective effects. In most studies exploring the rescue effects of Epo, apoptosis was exogenously induced by different cell death stimuli. Herein, we set out to study the expression and function of Epo in physiologically occurring apoptosis in a model of retinal development. We made use of an organotypic retinal wholemount culture system that resembles the physiological in vivo situation with cell connections still retained. Epo mRNA expression in the retina, liver, and kidney showed a significant increase during early development, coinciding with the anemia of the newborn. In the retina of Epo-green fluorescent protein transgenic mice, Epo-expressing cells were identified and found to be distributed in the retinal ganglion cell layer. Treatment of retinal wholemount cultures with recombinant Epo resulted in a significant decrease of apoptotic ganglion cells as well as photoreceptor cells throughout retinal development. Moreover, transforming growth factor-β-induced apoptosis was completely antagonized by Epo when both factors were simultaneously applied. Investigations on the signaling pathway revealed a decrease in Bax mRNA levels in Epo-treated retinal cells. We conclude that Epo exerts wide and prolonged neuroprotective activity in physiologically occurring apoptosis and thus contributes to proper retinal development.

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Neuroprotective Effects of Lindleyin on Hydrogen Peroxide-Induced Cell Injury and MPTP-Induced Parkinson’s Disease in C57BL/6 Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2938432 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Jin-Jie Zhang ◽

Xiao-Rong Shi ◽

Wen-Wen Lv ◽

Xiao-Long Zhou ◽

Ying-Dong Sun ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Hydrogen Peroxide ◽

Parkinson's Disease ◽

Cell Injury ◽

In Vivo Studies ◽

Antioxidant Enzyme Activities ◽

Apoptotic Pathway ◽

Neuroprotective Effects

Oxidative stress (OS) is a crucial factor influencing the development of Parkinson’s disease (PD). Here we first reported that Lindleyin (Lin), one of the major components of rhubarb, possessed neuroprotective effects against H2O2-induced SH-SY5Y cell injury and MPTP-induced PD of C57BL/6 mice. The results showed that Lin can decrease cell death and apoptotic rate induced by H2O2 through inhibiting mitochondrial apoptotic pathway and increasing the activities of SOD, GSH-Px, and CAT as well as decreasing the level of MDA. In addition, in vivo studies showed that oral administration of Lin (5 or 20 mg/kg) showed significant change in motor function deficits, antioxidant enzyme activities, apoptotic pathway, and tyrosine hydroxylase expression. Our results reveal that Lin might be a promising anti-PD agent by reducing OS and apoptosis.

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Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nek005 ◽

2006 ◽

Vol 3 (1) ◽

pp. 71-77 ◽

Cited By ~ 41

Author(s):

Yuta Inokuchi ◽

Masamitsu Shimazawa ◽

Yoshimi Nakajima ◽

Shinsuke Suemori ◽

Satoshi Mishima ◽

...

Keyword(s):

Oxidative Stress ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Water Soluble ◽

Retinal Damage ◽

Retinal Ganglion ◽

Neuroprotective Effects ◽

Brazilian Green Propolis

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

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Lipid nanoparticles enhance the absorption of cyclosporine A through the gastrointestinal barrier: In vitro and in vivo studies

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2016.01.037 ◽

2016 ◽

Vol 500 (1-2) ◽

pp. 154-161 ◽

Cited By ~ 16

Author(s):

Melissa Guada ◽

Beatriz Lasa-Saracíbar ◽

Hugo Lana ◽

Maria del Carmen Dios-Viéitez ◽

Maria J. Blanco-Prieto

Keyword(s):

Cyclosporine A ◽

Lipid Nanoparticles ◽

In Vivo Studies ◽

Gastrointestinal Barrier

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Neuroprotective Strategies for Neurological Disorders by Natural Products: An update

Current Neuropharmacology ◽

10.2174/1570159x16666180911124605 ◽

2019 ◽

Vol 17 (3) ◽

pp. 247-267 ◽

Cited By ~ 21

Author(s):

Muneeb U. Rehman ◽

Adil Farooq Wali ◽

Anas Ahmad ◽

Sheeba Shakeel ◽

Saiema Rasool ◽

...

Keyword(s):

Natural Products ◽

Large Scale ◽

Biological Properties ◽

In Vivo Studies ◽

Preclinical Models ◽

Neuroprotective Effects ◽

Neuroprotective Strategies ◽

Inflammatory Processes

Nature has bestowed mankind with surplus resources (natural products) on land and water. Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. These natural products have been experimentally documented to possess various biological properties such as antioxidant, anti-inflammatory and anti-apoptotic activities. In vitro and in vivo studies have further established the usefulness of natural products in various preclinical models of neurodegenerative disorders. Natural products include phytoconstituents, like polyphenolic antioxidants, found in herbs, fruits, nuts, vegetables and also in marine and freshwater flora. These phytoconstituents may potentially suppress neurodegeneration and improve memory as well as cognitive functions of the brain. Also, they are known to play a pivotal role in the prevention and cure of different neurodegenerative diseases, such as Alzheimer’s disease, epilepsy, Parkinson’s disease and other neuronal disorders. The large-scale neuro-pharmacological activities of natural products have been documented due to the result of either the inhibition of inflammatory processes, or the up-regulation of various cell survival proteins or a combination of both. Due to the scarcity of human studies on neuroprotective effects of natural products, this review focuses on the various established activities of natural products in in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications using the available knowledge in the literature.

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Vasculoprotective and Neuroprotective Effects of Various Parts of Pomegranate: In Vitro, In Vivo, and Preclinical Studies

10.5772/intechopen.96680 ◽

2021 ◽

Author(s):

Maria Trapali ◽

Vasiliki Lagouri

Keyword(s):

Ellagic Acid ◽

Therapeutic Agent ◽

Neuroprotective Effect ◽

Pomegranate Juice ◽

In Vivo Studies ◽

Neuroprotective Effects ◽

Hydrolysable Tannins ◽

Main Components

Pomegranate (Punica granatum L.) is one of the oldest edible fruits in the Mediterranean area and has been used extensively in the folk medicine. Popularity of pomegranate has increased especially in the last decade because of the health effects of the fruit. Polyphenols, represent the predominant class of phytochemicals of pomegranate, mainly consisting of hydrolysable tannins and ellagic acid. Pomegranate is a rich source of the ellagitannin punicalagin, which has aroused considerable interest in pomegranate fruit as a new therapeutic agent in recent years. Most studies on the effects of pomegranate juice have focused on its ability to cure diabetes and atherosclerosis. The present review summarizes some recent studies on the vasculoprotective and neuroprotective effect of various parts of pomegranate and its main compounds especially hydrolysable tannins ellagitannins, ellagic acid and their metabolites. The in vitro and in vivo studies, showed that the whole parts of pomegranate as well as its main components had a positive influence on blood glucose, lipid levels, oxidation stress and neuro/inflammatory biomarkers. They could be used as a future therapeutic agent towards several vascular and neurodegenerative disorders such as hypertension, coronary heart disease and Alzheimer.

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