Effects of neurosteroids on ischemia-reperfusion injury in the rat retina: role of sigma1 recognition sites.
The effects of neurosteroids, 17beta-estradiol and dehydroepiandrosterone-sulfate (DHEA-S), were investigated on retinal degeneration using a rat model of ischemia-reperfusion injury. The animals were anaesthetized and retinal ischemia was induced by elevating the intraocular pressure to 120 mm Hg for 45 min. Neurosteroids were injected intraperitoneally before ischemia and immediately after reperfusion. Retinal biochemical changes such as increase of lactate content and decrease of glucose and ATP were significantly inhibited by neurosteroids compared to the control ischemic group. The effects of 17beta-estradiol and DHEA-S were antagonized by pre-treatment with the sigma1 site antagonist. These findings suggest that 17beta-estradiol and dehydroepiandrosterone-sulfate may affect the metabolic state of surviving neurons and glial cells after ischemic injury and that they act, at least in part, through involvement of sigma1 recognition sites.
Bucolo
Claudio
C
Department of Experimental and Clinical Pharmacology, School of Medicine, University of Catania, Viale A. Doria 6, Catania I-95125, Italy.
Drago
Filippo
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019314:Dehydroepiandrosterone Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007773:Lactates / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012162:Retinal Degeneration / Q000209:etiology / Q000517:prevention & control*
D005029:Ethylenediamines; D007773:Lactates; D009025:Morpholines; D017480:Receptors, sigma; C101491:sigma1-binding protein, rat; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D000255:Adenosine Triphosphate; D005947:Glucose