Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush

Zhang, Z.Z.; Gong, Yuanyuan; Shi, Yuhua; Zhang, W.; Qin, Xiuhong; Wu, Xinming

doi:10.1016/j.neuroscience.2012.07.056

Cited by 49 publications

(49 citation statements)

References 55 publications

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“…40e42 In the retina, VPA upregulated the expression of BDNF and TrkB after optic nerve injury, and there was an increased acetylation level of histone H3 accompanied by increased transcriptional activity of the BDNF promoter in the retina. 43 These results suggest that the VPA-mediated up-regulation of BDNF in Müller cells observed in the present study is likely due to elevated BDNF promotor activity through direct inhibition of histone deacetylase. Neuroprotection by stimulation of BDNFeTrkB signaling has been well established.…”

Section: Discussionsupporting

confidence: 59%

“…Previous studies have indicated that VPA protects RGCs from optic nerve injuryeinduced cell death. 43,61 The optic nerve injury model is an animal model of glaucoma that allows investigation of mechanisms underlying death of retinal neurons, 34,62 but this model is not sufficient to represent fully the pathogenesis of glaucoma. It would therefore be worthwhile to investigate whether VPA can ameliorate glaucomatous retinal degeneration in other animal models of glaucoma.…”

Section: Discussionmentioning

confidence: 99%

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Valproic Acid Prevents NMDA-Induced Retinal Ganglion Cell Death via Stimulation of Neuronal TrkB Receptor Signaling

Kimura

Namekata

Guo

et al. 2015

The American Journal of Pathology

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Valproic acid (VPA) is widely prescribed for treatment of epilepsy, mood disorders, migraines, and neuropathic pain. It exerts its therapeutic benefits through multiple mechanisms, including enhancement of GABAergic activity, activation of prosurvival protein kinases, and inhibition of histone deacetylase. Increasing evidence suggests that VPA possesses neuroprotective properties. We examined neuroprotective effects of VPA in an N-methyl-d-aspartate (NMDA) excitotoxicity model, which mimics some of the pathological features of glaucoma. In vivo retinal imaging using optical coherence tomography revealed that NMDA-induced retinal degeneration was suppressed in the VPA-treated retina, and histological analyses confirmed that VPA reduced retinal ganglion cell death. In vivo electrophysiological analyses demonstrated that visual impairment was prevented in the VPA-treated retina, clearly establishing both histological and functional effects of VPA. Brain-derived neurotrophic factor (BDNF) expression was up-regulated in Müller glial cells, and neuroprotective effects of VPA on retinal ganglion cells were significantly reduced in a conditional knockout mouse strain with deletion of tropomyosin receptor kinase B (TrkB), a receptor for BDNF from retinal ganglion cells. The results show that VPA stimulates BDNF up-regulation in Müller glial cells and provides direct evidence that neuronal TrkB is important in VPA-mediated neuroprotection. Also, VPA suppresses oxidative stress induced by NMDA in the retina. Our findings raise intriguing possibilities that the widely prescribed drug VPA may be useful for treatment of glaucoma.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Valproic Acid Prevents NMDA-Induced Retinal Ganglion Cell Death via Stimulation of Neuronal TrkB Receptor Signaling

Kimura

Namekata

Guo

et al. 2015

The American Journal of Pathology

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“…In this study, we show that VPA increases ERK phosphorylation in the glaucomatous eye. VPA has been reported to exert neuroprotective effects by stimulating the ERK pathway in cortical neurons [11] and in the retina following optic nerve injury [4,43]. VPA stimulates ERK phosphorylation through a mechanism that is independent of HDAC inhibition, and suppresses apoptosis [23], suggesting that VPA may exert a direct effect on ERK activation.…”

Section: Discussionmentioning

confidence: 99%

“…For example, we previously reported that VPA upregulates Müller glial brain-derived neurotrophic factor (BDNF) and nerve growth factor, neurotrophic factors important for cell survival [12,13,20] and these effects may also apply to the VPA-treated GLAST KO mouse retina. Also, VPA is an effective HDAC inhibitor [8,30] and increased histone acetylation is associated with VPA-mediated neuroprotection [1,3,35,40,43]. These findings urge to identify genes and pathways that are modulated by HDAC inhibition and are involved in VPA-mediated RGC protection.…”

Section: Discussionmentioning

confidence: 99%

Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma

Kimura

Guo

Noro

et al. 2015

Neuroscience Letters

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“…Tissue sections were processed for routine Hematoxylin and Eosin following the methods of Zhang et al (2012) [13] to demonstrate the general morphology of the prostate tissue.…”

Section: Histologymentioning

confidence: 99%

Cell Proliferation and Epithelia Profile in Prostate Cancer and Benign Prostatic Hyperplasia

O.M.¹,

P.T.²,

D.T.³

et al. 2014

TOCJ

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Abstract:Objectives: Prostate cancer (PCa) and Benign Prostatic Hyperplasia (BPH) are the leading cause of urinary tract disorders in males both of which are characterized by rapid proliferation of cells. This study characterizes both Ki-67 and E-Cadherin profiles in BPH and PCa biopsies to determine and compare the extent of aggressiveness of cell proliferation in BPH and PCa.Method: Biopsies were collected from patients clinically diagnosed to be suffering from PCa or BPH and were immunohistochemically labelled using Anti-Ki-67 and Anti-ECAD monoclonal antibodies. The sections were treated with urea followed by incubation in a microwave to activate the antigens. Primary antibody treatment was done in biotinylated goat serum, blocking was done with bovine serum albumin (BSA) and finally secondary antibody staining using Anti-Ki-67 and Anti-ECAD monoclonal antibodies. Results:The expression level of Ki-67 corresponded to the rate of proliferation and size of the tumor cell mass in both PCa and BPH. ECAD expression was highly positive in BPH and less positive in PCa-showing onset of malignancy in PCa. Certain cell clumps (metastases) stained highly positive to Ki-67 and were located at random intervals within the tissue of PCa biopsies, this type of distribution also coincided with ECAD immunonegativity. Conclusion:Ki-67 expression indicates the rate of cell proliferation and the aggressiveness of such tumors, while ECAD shows defective cytoskeleton and extent of malignancy. Correlating ECAD and Ki-67 gives a direct relationship between the rate of cell division, tumor invasion and epithelia structure. This also covers both glandular and fibromuscular epithelium

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Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush

Cited by 49 publications

References 55 publications

Valproic Acid Prevents NMDA-Induced Retinal Ganglion Cell Death via Stimulation of Neuronal TrkB Receptor Signaling

Valproic Acid Prevents NMDA-Induced Retinal Ganglion Cell Death via Stimulation of Neuronal TrkB Receptor Signaling

Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma

Cell Proliferation and Epithelia Profile in Prostate Cancer and Benign Prostatic Hyperplasia

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