Some histological and metabolic properties of an isolated perfused rat brain preparation with special reference to monoamine metabolism.
A method is described for perfusing the rat head which results in perfusion of the brain, its covering and the bony skull only. Dye and latex injection studies showed that there was no perfusion of extracranial tissue and thus it was not necessary to remove the lower jaw and facial tissues as described by previous authors. Perfusion with fluorescein demonstrated that the whole brain was perfused. Light microscopy after two hours of perfusion revealed no deterioration in brain-structure. Electron microscopy showed a small increase in the extracellular space and the perivascular space with good preservation of subcellular organelles. Glucose and acetoacetate removal were very similar to those reported for the adult rat in vivo as measured by arterio-venous differences. The concentrations of 5-hydroxytryptamine, dopamine and noradrenaline are maintained at values close to those in vivo during a 2-hr perfusion with a basal medium and the preparation will maintain linear rates of 5-hydroxytryptamine synthesis for 2 h when the medium contains L-tryptophan and tranylcypromine, at rates similar to those measured in vivo. The rate of uptake of L-tryptophan into the brain is similar to that reported after L-tryptophan loading in vivo. The histological and metabolic properties of the preparation are close to those observed in vivo. The method could provide a way in which monoamine metabolism in particular could be studied using an experimental model closer in its properties to the in vivo situation than tissue preparations such as slices or homogenates.
Woods
H F
HF
Medical Research Council Unit and University, Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford OX2 6HE, U.K.
Graham
C W
CW
Green
A R
AR
Youdim
M B
MB
Grahame-Smith
D G
DG
Hughes
J T
JT
D000090:Acetoacetates / Q000378:metabolism / Q000493:pharmacokinetics; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002536:Cerebral Arteries / Q000033:anatomy & histology / Q000502:physiology / Q000601:surgery*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004396:Coloring Agents / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D007840:Latex / Q000493:pharmacokinetics; D008297:Male; D008854:Microscopy, Electron; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019635:Neurosurgical Procedures; D010477:Perfusion / Q000295:instrumentation / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D014343:Trypan Blue / Q000493:pharmacokinetics
D000090:Acetoacetates; D000596:Amino Acids; D015306:Biogenic Monoamines; D004396:Coloring Agents; D007840:Latex; D014343:Trypan Blue; D005947:Glucose