title: Effects of the radical scavenger AVS on behavioral and BBB changes after experimental subarachnoid hemorrhage.
abstract: Free radicals are important contributors to the global brain dysfunction that follows subarachnoid hemorrhage (SAH). We evaluated the effects of hydroxyl radical scavenger AVS [(+/-)-N,N'-propylenedinicotinamide; Nicaraven] after experimental SAH on rodent behavioral deficits (employing a battery of well-characterized assessment tasks over a 2-day observation period) and blood-brain barrier (BBB) permeability changes two days after SAH (quantifying the microvascular alterations according to the extravasation of protein-bound Evans Blue using a spectrophotofluorimetric technique) in dose-response and time-window experiments. Groups of 10 rats were injected with 400 microl of autologous blood into the cisterna magna, and followed by intravenous continuous infusion of saline or 0.1, 03 or 1 mg/kg/min of AVS beginning within 5 minutes or 6 or 12 hours after SAH. The results were compared with sham-operated saline-treated and with SAH saline-treated animals. AVS significantly ameliorated performances on Beam Balance (p < 0.01) and decreased BBB permeability changes in frontal, temporal, parietal, occipital and cerebellar cortices and subcortical and cerebellar nuclei and brainstem (p < 0.01), but did not significantly affect changes in Beam Walking. This study demonstrates the neuroprotective effects of AVS when administered after experimental SAH in rats. These effects were dose-dependent and, moreover, were evident within the therapeutic window of 6-12 hours after SAH. These results reinforce the concept of a participation of reactive oxygen intermediates in the cerebral dysfunction following SAH.
authors.affiliation: Institute of Pharmacology, University of Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Imperatore
authors.forename: A
authors.initials: A
authors.lastname: Germanò
authors.forename: D
authors.initials: D
authors.lastname: d'Avella
authors.forename: F
authors.initials: F
authors.lastname: Tomasello
authors.forename: G
authors.initials: G
authors.lastname: Costa
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000473:pathology* / Q000523:psychology*; D013997:Time Factors; D016138:Walking / Q000502:physiology
chemical_list: D016166:Free Radical Scavengers; D009536:Niacinamide; C042625:nicaraven