Biomaterial Database

The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. 1988

C K Park, and D G Nehls, and D I Graham, and G M Teasdale, and J McCulloch

Wellcome Neuroscience Group, University of Glasgow, UK.

Excessive activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor has been implicated in the sequence of neurochemical events that results in irreversible neuronal damage in cerebral ischemia. The effects of the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) upon the amount of ischemic brain damage has been assessed quantitatively in the lightly anesthetized rat. Focal cerebral ischemia was produced by the permanent occlusion of one middle cerebral artery (MCA), and the animals were killed 3 hours after the arterial occlusion. MK-801 (0.5 mg/kg) was administered intravenously either 30 minutes prior to MCA occlusion or 30 minutes after the induction of ischemia. Pretreatment with MK-801 reduced the volume of ischemic damage both in the cerebral cortex (by 38% compared with untreated rats with MCA occlusion; p less than 0.01) and in the caudate nucleus (by 18% compared with controls; p less than 0.05). Treatment with MK-801, initiated 30 minutes after MCA occlusion, reduced the volume of ischemic damage in the cerebral cortex (by 52% compared with controls; p less than 0.01). The volume of ischemic damage in the caudate nucleus was minimally influenced by MK-801 treatment initiated after MCA occlusion. The antiischemic effects of MK-801 were readily demonstrable despite the hypotension that MK-801 induced in rats anesthetized with halothane (0.5%), nitrous oxide (70%), and oxygen (30%). The potency of MK-801 in reducing ischemic brain damage, even when administered after the induction of ischemia, highlights the potential use of NMDA receptor antagonists for the treatment of focal cerebral ischemia in humans.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001794	Blood Pressure	PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.	Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
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
D003986	Dibenzocycloheptenes	A family of tricyclic hydrocarbons whose members include many of the commonly used tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC).
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
D016291	Dizocilpine Maleate	A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.	Dizocilpine,MK-801,MK 801,MK801
D017470	Receptors, Glutamate	Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.	Excitatory Amino Acid Receptors,Glutamate Receptors,Receptors, Excitatory Amino Acid,Excitatory Amino Acid Receptor,Glutamate Receptor,Receptor, Glutamate
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D017981	Receptors, Neurotransmitter	Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.	Neurohumor Receptors,Neuromediator Receptors,Neuromodulator Receptors,Neuroregulator Receptors,Receptors, Neurohumor,Receptors, Synaptic,Synaptic Receptor,Synaptic Receptors,Neuromediator Receptor,Neuromodulator Receptor,Neuroregulator Receptor,Neurotransmitter Receptor,Receptors, Neuromediators,Receptors, Neuromodulators,Receptors, Neuroregulators,Receptors, Neurotransmitters,Neuromediators Receptors,Neuromodulators Receptors,Neuroregulators Receptors,Neurotransmitter Receptors,Neurotransmitters Receptors,Receptor, Neuromediator,Receptor, Neuromodulator,Receptor, Neuroregulator,Receptor, Neurotransmitter,Receptor, Synaptic,Receptors, Neuromediator,Receptors, Neuromodulator,Receptors, Neuroregulator