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Pavlina Tsoka, Ioannis Charalampopoulos, Achilleas Gravanis, Demetrios Vavvas, Miltiadis Tsilimbaris; Neuroprotective Effect of DHEA-derivative BNN27 against N-Methyl-D-Aspartate-induced Retinal Excitotoxicity in Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3250.
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To investigate the neuroprotective role of a novel synthetic analogue (BNN27) of Dehydroepiandrosterone in an experimental model of N-methyl-D-aspartate induced (NMDA) retinal excitotoxicity in mice after intraperitoneal submission. BNN27 passes through the blood-brain barrier and interact with nerve growth factor (NGF) receptors, TrkA and p75.
Six to eight week old C57BL/6 mice were used. NMDA 100mg/ml (2 μl) was injected intravitreal with a 33g Hamilton syringe in deeply anesthetized animals. Animals were treated daily with IP injections of BNN27 (40mg/kg or 100mg/kg) or ethanol vehicle. Mice were sacrificed 24 and 72 hours later. TUNEL staining was performed in order to evaluate cellular death. Six animals per group and time point were evaluated.
NMDA induced apoptotic cell death was similar 24 and 72 hours after intravitreal administration (36±4 and 42±6 TUNEL positive cells/section respectively. (mean ± SD). Treatment resulted in a dose dependent reduction in TUNEL positive cells in the ganglion cell layer both in 24 and 72 hours after NMDA induced retinal excitotoxicity. Treatment with 40mg/kg of BNN27 reduced TUNEL positive cells to 22±4 and 25±4 TUNEL positive cells/section, while BNN27 at 100mg/kg significantly reduced TUNEL positive cells to 13±2 cells/section and 8±2 cells/section at 24 and 72 hours after NMDA intravitreal injection respectively.
BNN27 appears to exert anti-apoptotic effects in NMDA retinal excitotoxicity induced apoptosis, possibly through its interaction with NGF receptors, representing a potential lead molecule to develop new neuroprotective agents for retina degeneration.
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