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Titolo:
Screening for cerebroprotective agents using an in vivo model of cerebral reversible depolarization in awake rats
Autore:
Bodo, M; Perjes, G; Kalman, E; Bacskai, E; Berko, K; Sarkadi, A; Nagy, I; Keim, KL; Matysik, FM; Csomor, K; McCarron, R; Zagvazdin, Y; Rosenthal, M; Morrissette, C; Herendy, E; Szporny, L; Nagy, Z;
Indirizzi:
Walter Reed Army Inst Res, Dept Resuscitat Med, Silver Spring, MD 20910 USA Walter Reed Army Inst Res Silver Spring MD USA 20910 Spring, MD 20910 USA Richter Ltd, Chem Works Gedeon, H-11030 Budapest, Hungary Richter Ltd Budapest Hungary H-11030 s Gedeon, H-11030 Budapest, Hungary Vela Pharmaceut, Princeton, NJ 08540 USA Vela Pharmaceut Princeton NJ USA08540 harmaceut, Princeton, NJ 08540 USA Univ Leipzig, D-04103 Leipzig, Germany Univ Leipzig Leipzig Germany D-04103 v Leipzig, D-04103 Leipzig, Germany USN, Med Res Ctr, Silver Spring, MD 20910 USA USN Silver Spring MD USA 20910 , Med Res Ctr, Silver Spring, MD 20910 USA Southeastern Univ, NOVA, Coll Med Sci, Ft Lauderdale, FL 33328 USA Southeastern Univ Ft Lauderdale FL USA 33328 Ft Lauderdale, FL 33328 USA Univ Miami, Sch Med, Miami, FL 33101 USA Univ Miami Miami FL USA 33101Univ Miami, Sch Med, Miami, FL 33101 USA Natl Stroke Ctr, H-1021 Budapest, Hungary Natl Stroke Ctr Budapest Hungary H-1021 ke Ctr, H-1021 Budapest, Hungary
Titolo Testata:
PHARMACOLOGICAL RESEARCH
fascicolo: 5, volume: 44, anno: 2001,
pagine: 419 - 429
SICI:
1043-6618(200111)44:5<419:SFCAUA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHARMACEUTICAL-INDUSTRY; NEUROPROTECTIVE AGENTS; EVOKED-RESPONSES; BRAIN-DAMAGE; ISCHEMIA; HYPOXIA; DRUGS; EEG; PATHOPHYSIOLOGY; ARTERIAL;
Keywords:
pharmaceutical screening; hypoxia; isoelectric EEG; reversible depolarization; awake rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
82
Recensione:
Indirizzi per estratti:
Indirizzo: Bodo, M Walter Reed Army Inst Res, Dept Resuscitat Med, 503 Robert Grant Ave,Rm 1N46, Silver Spring, MD 20910 USA Walter Reed Army Inst Res 503 Robert Grant Ave,Rm 1N46 Silver Spring MD USA 20910
Citazione:
M. Bodo et al., "Screening for cerebroprotective agents using an in vivo model of cerebral reversible depolarization in awake rats", PHARMAC RES, 44(5), 2001, pp. 419-429

Abstract

The need to screen cerebroprotective compounds without anesthetic interference prompted the development of a model using hypoxic rats. In this model two outcome measures were used: (1) the time to reach isoelectric electroencephalogram (iEEG), caused by nitrogen gas inhalation in the test chamber, and (2) the time for behavioral recovery measuring the latency of restoration of the head-ithdrawal reflex upon vibrissae stimulation. We report here data of blood chemistry, cerebral tissue oxygen measurements, a definition of a proposed scoring system, and the pharmacological results of RGH-2202. The findings with RGH-2202 are used here to show the utility of the screening method. Events during hypoxia: Arterial and venous pO(2), pCO(2), and pH, and brain tissue pO(2) significantly declined. Significant correlations were established among the pO(2) of cerebral tissue, blood, and the test chamber. RGH-2202 significantly and dose-dependently shortened the iEEG time; the compound's Effective Dose(30) was 227.8 mg kg(-1). Events during recovery: Immediately after the iEEG, when the atmosphere inthe chamber was replaced with room air, the arterial, venous and brain tissue pO(2) increased above the control level and subsequently recovered to baseline levels. Behavioral recovery occurred before blood chemistry was otherwise normalized. RGH-2202 significantly and dose-dependently shortened the recovery time; the Effective Dose(30) was 8.71 mg kg(-1). The available data define and support the physiological basis of this practicable rat-screening model. (C) 2001 Academic Press.

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Documento generato il 11/07/20 alle ore 15:58:54