PURPOSES: To investigate whether valproic acid (VPA) has a neuroprotective effect against ischemia/reperfusion (I/R) injury in the rat retina, and to elucidate the potential antioxidant mechanisms involved. METHODS: Adult male Wistar rats were randomly divided into four groups: sham (group A), sham plus VPA (group B), I/R plus vehicle (group C), and I/R plus VPA (group D). Retinal I/R injury was produced by inducing an exceedingly high intraocular pressure (IOP). Prior to insult, VPA was administered subcutaneously (300 mg/kg twice daily) for 7 days, after which the animal was sacrificed. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. Protein expressions of retinal poly(ADP-ribose) (PAR) and nitrotyrosine (NT) were analyzed by Western blotting 24 h after injury. Apoptosis of retinal cells was evaluated 24 h after I/R injury by immunofluorescence of activated caspase-3 in histological sections of retina. Seven days after reperfusion, electroretinography (ERG) was performed, and retinal histological changes were examined by light microscopy. RESULTS: Following ischemia, the thickness of the entire retina, including the inner nuclear layer (INL) and inner plexiform layer (IPL), as well as the number of cells in the ganglion cell layer (GCL) were significantly greater in group D than in group C (p < 0.05). VPA suppressed I/R-induced reductions in ERG a- and b-wave amplitudes (p < 0.05). VPA attenuated I/R-induced activation of caspase-3 in ganglion cells and INL cells (p < 0.001). VPA significantly decreased MDA levels and increased activities of SOD, GSH-Px, and CAT in group D (p < 0.05). VPA attenuated activation of PAR and accumulation of NT in the retina after I/R (p < 0.01). CONCLUSIONS: VPA protects the retina from I/R injury by enhancing anti-oxidative effects and inhibiting apoptosis of retinal cells.
PURPOSES: To investigate whether valproic acid (VPA) has a neuroprotective effect against ischemia/reperfusion (I/R) injury in the rat retina, and to elucidate the potential antioxidant mechanisms involved. METHODS: Adult male Wistar rats were randomly divided into four groups: sham (group A), sham plus VPA (group B), I/R plus vehicle (group C), and I/R plus VPA (group D). Retinal I/R injury was produced by inducing an exceedingly high intraocular pressure (IOP). Prior to insult, VPA was administered subcutaneously (300 mg/kg twice daily) for 7 days, after which the animal was sacrificed. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. Protein expressions of retinal poly(ADP-ribose) (PAR) and nitrotyrosine (NT) were analyzed by Western blotting 24 h after injury. Apoptosis of retinal cells was evaluated 24 h after I/R injury by immunofluorescence of activated caspase-3 in histological sections of retina. Seven days after reperfusion, electroretinography (ERG) was performed, and retinal histological changes were examined by light microscopy. RESULTS: Following ischemia, the thickness of the entire retina, including the inner nuclear layer (INL) and inner plexiform layer (IPL), as well as the number of cells in the ganglion cell layer (GCL) were significantly greater in group D than in group C (p < 0.05). VPA suppressed I/R-induced reductions in ERG a- and b-wave amplitudes (p < 0.05). VPA attenuated I/R-induced activation of caspase-3 in ganglion cells and INL cells (p < 0.001). VPA significantly decreased MDA levels and increased activities of SOD, GSH-Px, and CAT in group D (p < 0.05). VPA attenuated activation of PAR and accumulation of NT in the retina after I/R (p < 0.01). CONCLUSIONS:VPA protects the retina from I/R injury by enhancing anti-oxidative effects and inhibiting apoptosis of retinal cells.
Authors: João Martins; Filipe Elvas; Dan Brudzewsky; Tânia Martins; Bogdan Kolomiets; Pedro Tralhão; Casper R Gøtzsche; Cláudia Cavadas; Miguel Castelo-Branco; David P D Woldbye; Serge Picaud; Ana R Santiago; António F Ambrósio Journal: ASN Neuro Date: 2015-08-26 Impact factor: 4.146
Authors: Ryan W Speir; Jonathan D Stallings; Jared M Andrews; Mary S Gelnett; Timothy C Brand; Shashikumar K Salgar Journal: PLoS One Date: 2015-05-13 Impact factor: 3.240
Authors: José Christian Machado Ximenes; Kelly Rose Tavares Neves; Luzia Kalyne A M Leal; Marta Regina Santos do Carmo; Gerly Anne de Castro Brito; Maria da Graça Naffah-Mazzacoratti; Ésper Abrão Cavalheiro; Glauce Socorro de Barros Viana Journal: J Neurodegener Dis Date: 2015-02-19
Authors: Hong Pan; Meihua He; Ruixing Liu; Nicholas C Brecha; Albert Cheung Hoi Yu; Mingliang Pu Journal: PLoS One Date: 2014-12-03 Impact factor: 3.240
Authors: Jaclyn Y Bermudez; Hannah C Webber; Gaurang C Patel; Xiangyang Liu; Yi-Qiang Cheng; Abbot F Clark; Weiming Mao Journal: Invest Ophthalmol Vis Sci Date: 2016-07-01 Impact factor: 4.925