Biomaterial Database

Comparative analysis of brain protection by N-methyl-D-aspartate receptor antagonists after transient focal ischemia in cats. 1997

M Miyabe, and J R Kirsch, and T Nishikawa, and R C Koehler, and R J Traystman

Department of Anesthesiology and Critical Care Medicino, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

OBJECTIVE We tested the hypothesis that the administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 2R,4R,5S-(2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid) (NPC 17742) or cis-4-(phosphonomethyl) piperidine-2-carboxylic acid (CGS 19755) or the noncompetitive NMDA receptor antagonist dizocilpine (MK-801), at the appropriate doses, would all have efficacy in decreasing early postischemic brain injury in a feline model of transient focal ischemia. METHODS Prospective, randomized, controlled animal trial. METHODS University research laboratory. METHODS Forty mixed-breed cats. METHODS Halothane-anesthetized cats underwent 90 mins of left middle cerebral artery occlusion plus 4 hrs of reperfusion. At 75 mins of ischemia, control cats received intravenous saline (n = 10). Experimental cats (n = 10 in each group) were treated with NPC 17742 (5 mg/kg bolus and 2.5 mg/kg/hr throughout reperfusion), MK-801 (5 mg/kg intravenous bolus), or CGS 19755 (40 mg/kg intravenous bolus) in a randomized fashion. RESULTS Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia, and recovered to the same extent during early reperfusion, in the four groups. Triphenyltetrazolium-determined injury volume of the ipsilateral caudate nucleus in cats treated with NPC 17742 (105 +/- 25 [SEM] mm3), MK-801 (97 +/- 22 mm3), and CGS 19755 (97 +/- 13 mm3) was less than in control cats (198 +/- 21 mm3). Hemisphere injury volumes with NPC 17742 (1209 +/- 405 mm3) and MK-801 (1338 +/- 395 mm3) were less than that value in controls (2193 +/- 372 mm3), whereas injury volume with CGS 19755 (1553 +/- 519 mm3) treatment did not attain significance (p < .09). CONCLUSIONS NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions after 90 mins of transient focal ischemia in the cat. At the doses chosen, there appear to be no major differences in therapeutic efficacy for competitive and noncompetitive NMDA receptor antagonists.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010875	Pipecolic Acids		Acids, Pipecolic
D011446	Prospective Studies	Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.	Prospective Study,Studies, Prospective,Study, Prospective
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D001925	Brain Damage, Chronic	A condition characterized by long-standing brain dysfunction or damage, usually of three months duration or longer. Potential etiologies include BRAIN INFARCTION; certain NEURODEGENERATIVE DISORDERS; CRANIOCEREBRAL TRAUMA; ANOXIA, BRAIN; ENCEPHALITIS; certain NEUROTOXICITY SYNDROMES; metabolic disorders (see BRAIN DISEASES, METABOLIC); and other conditions.	Encephalopathy, Chronic,Chronic Encephalopathy,Chronic Brain Damage
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002546	Ischemic Attack, Transient	Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6)	Brain Stem Ischemia, Transient,Cerebral Ischemia, Transient,Crescendo Transient Ischemic Attacks,Transient Ischemic Attack,Anterior Circulation Transient Ischemic Attack,Brain Stem Transient Ischemic Attack,Brain TIA,Brainstem Ischemia, Transient,Brainstem Transient Ischemic Attack,Carotid Circulation Transient Ischemic Attack,Posterior Circulation Transient Ischemic Attack,TIA (Transient Ischemic Attack),Transient Ischemic Attack, Anterior Circulation,Transient Ischemic Attack, Brain Stem,Transient Ischemic Attack, Brainstem,Transient Ischemic Attack, Carotid Circulation,Transient Ischemic Attack, Posterior Circulation,Transient Ischemic Attack, Vertebrobasilar Circulation,Transient Ischemic Attacks, Crescendo,Vertebrobasilar Circulation Transient Ischemic Attack,Attack, Transient Ischemic,Attacks, Transient Ischemic,Brainstem Ischemias, Transient,Cerebral Ischemias, Transient,Ischemia, Transient Brainstem,Ischemia, Transient Cerebral,Ischemias, Transient Brainstem,Ischemias, Transient Cerebral,Ischemic Attacks, Transient,TIA, Brain,TIAs (Transient Ischemic Attack),Transient Brainstem Ischemia,Transient Cerebral Ischemia,Transient Cerebral Ischemias,Transient Ischemic Attacks
D002560	Cerebrovascular Circulation	The circulation of blood through the BLOOD VESSELS of the BRAIN.	Brain Blood Flow,Regional Cerebral Blood Flow,Cerebral Blood Flow,Cerebral Circulation,Cerebral Perfusion Pressure,Circulation, Cerebrovascular,Blood Flow, Brain,Blood Flow, Cerebral,Brain Blood Flows,Cerebral Blood Flows,Cerebral Circulations,Cerebral Perfusion Pressures,Circulation, Cerebral,Flow, Brain Blood,Flow, Cerebral Blood,Perfusion Pressure, Cerebral,Pressure, Cerebral Perfusion
D000596	Amino Acids	Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.	Amino Acid,Acid, Amino,Acids, Amino
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia