RESUMEN
PURPOSE: The purpose of this study was to analyze the neuroprotective effect of an α7 nAChR agonist, PNU-282987, using an in vivo model of glaucoma in Long Evans rats. METHODS: One eye in each animal was surgically manipulated to induce glaucoma in control untreated animals and in animals that were treated with intravitreal injections of PNU-282987. To induce glaucoma-like conditions, 0.05 mL of 2 M NaCl was injected into the episcleral veins of right eyes in each rat to create scar tissue and increase intraocular pressure. The left eye in each rat acted as an internal control. One month following NaCl injection, rats were euthanized, retinas were removed, flatmounted, fixed, and nuclei were stained with cresyl violet or RGCs were immunostained with an antibody against Thy 1.1 or against Brn3a. Stained nuclei in the RGC layer and labeled RGCs in NaCl-injected retinas were counted and compared with cell counts from untreated retinas in the same animal. RESULTS: NaCl injections into the episcleral veins caused a significant loss of cells by an average of 27.35% (± 2.12 SEM) in the RGC layer within 1 month after NaCl injection, which corresponded to a significant loss of RGCs. This loss of RGCs was eliminated if 5 µL of 100 µM PNU-282987 was injected into the right eye an hour before NaCl injection. CONCLUSIONS: The results from this study support the hypothesis that the α7 agonist, PNU-282987, has a neuroprotective effect in the rat retina. PNU-282987 may be a viable candidate for future therapeutic treatments of glaucoma.
Asunto(s)
Benzamidas/uso terapéutico , Compuestos Bicíclicos con Puentes/uso terapéutico , Glaucoma/prevención & control , Agonistas Nicotínicos/uso terapéutico , Enfermedades del Nervio Óptico/prevención & control , Degeneración Retiniana/prevención & control , Células Ganglionares de la Retina/efectos de los fármacos , Animales , Recuento de Células , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Femenino , Glaucoma/inducido químicamente , Glaucoma/patología , Inyecciones Intravítreas , Masculino , Fármacos Neuroprotectores/uso terapéutico , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/patología , Ratas , Ratas Long-Evans , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/patología , Células Ganglionares de la Retina/patología , Espectrometría de Masas en Tándem , Tonometría Ocular , Receptor Nicotínico de Acetilcolina alfa 7/agonistasRESUMEN
The purpose of the present study was to provide further information about the effects of gamma-hydroxybutyrate (GHB) on memory. Initially, the acute effects of gamma-butyrolactone (GBL, 75-200 mg/kg IP), 1,4-butanediol (1,4-BD, 100-300 mg/kg IP), and ethanol (1.0-3.0 g/kg, oral), as well as GHB (100-300 mg/kg IP), were examined in rats responding under a delayed-matching-to-position (DMTP) procedure with delays from 0 to 32 s. Acute administration of all four drugs reduced the number of trials completed and also reduced accuracy during delay trials, but not during trials without a delay. Some tolerance developed to the disruptive effects of GHB following exposure to 300 mg/kg/day for 29 consecutive days. These data indicate that GHB can disrupt working memory and speed of responding, and that tolerance can develop to these effects. Moreover, the acute effects of GHB under the DMTP procedure resemble those of its metabolic precursors, GBL and 1,4-BD, and of the prototypical CNS depressant drug, ethanol.
