Neuroprotection by trans-resveratrol in rats with N-methyl-D-aspartate (NMDA)–induced retinal injury: Insights into the role of adenosine A1 receptors

• Published in: Neuroscience research 2023-08, Vol.193, p.1-12
• Main Authors: Abd Ghapor, Afiqq Aiman, Abdul Nasir, Nurul Alimah, Iezhitsa, Igor, Agarwal, Renu, Razali, Norhafiza
• Format: Article
• Language: English
• Subjects: 1,3-Dipropyl-8-cyclopentylxanthine; Adenosine A1 receptors; Animals; N-Methylaspartate - toxicity; Neuroprotection; Oxidative and nitrosative stress; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A1; Receptors, N-Methyl-D-Aspartate; Resveratrol; Retinal and optic nerve damage; Trans-resveratrol, N-methyl-D-aspartate, retinal excitotoxicity
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2023.02.004

Adenosine A1 receptors (AA1R) have been shown to counteract N-methyl-D-aspartate (NMDA)–mediated glutamatergic excitotoxicity. In the present study, we investigated the role of AA1R in neuroprotection by trans-resveratrol (TR) against NMDA-induced retinal injury. In total, 48 rats were divided into the following four groups: normal rats pretreated with vehicle; rats that received NMDA (NMDA group); rats that received NMDA after pretreatment with TR; and rats that received NMDA after pretreatment with TR and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an AA1R antagonist. Assessment of general and visual behaviour was performed using the open field test and two-chamber mirror test, respectively, on Days 5 and 6 post NMDA injection. Seven days after NMDA injection, animals were euthanized, and eyeballs and optic nerves were harvested for histological parameters, whereas retinae were isolated to determine the redox status and expression of pro- and anti-apoptotic proteins. In the present study, the retinal and optic nerve morphology in the TR group was protected from NMDA-induced excitotoxic damage. These effects were correlated with the lower retinal expression of proapoptotic markers, lipid peroxidation, and markers of nitrosative/oxidative stress. The general and visual behavioural parameters in the TR group showed less anxiety-related behaviour and better visual function than those in the NMDA group. All the findings observed in the TR group were abolished by administration of DPCPX. •Adenosine A1 receptors (AA1R) involves in retinal protection by trans-resveratrol (TR).•TR improves visual behaviour in rats with NMDA-induced retinal injury.•AA1R-mediated neuroprotection by TR is associated with reduced oxidative stress.•AA1R-mediated neuroprotection by TR is associated with reduced nitrosative stress.•AA1R-mediated neuroprotection by TR is associated with reduced apoptosis.