Preservation of integrative function in a perfused guinea pig brain.
The mammalian brain has been one of the most difficult organs to maintain using artificial perfusion. Normal biochemistry, histology, and electrophysiology of the brain have been demonstrated for limited periods in vitro, but it has been more difficult to maintain complex, integrative neuronal activity such as the electroencephalogram (EEG) or programmed motor output. Normal motor output, other than reflex activity, has not previously been demonstrated in a perfused brain preparation. This paper reports the first preservation of normal function in a complete motor network, including intact afferent and efferent pathways, during perfusion of the mammalian brain. The brain, rostral spinal cord and peripheral nervous system of the guinea pig were perfused in situ using an artificial blood containing the oxygen carrier, perfluorotributylamine (FC-43). This preparation was maintained normothermic, whereas many other perfused brain preparations have been maintained hypothermic to prolong viability. Survival was enhanced by the addition of HEPES buffer to the perfusion medium, probably by increasing carbon dioxide transport. The duration of normal EEG was extended to 8 h. Spontaneous respiratory motor output with normal waveform and temporal pattern was recorded from the phrenic nerve for an average of 6 h. The respiratory motor output responded appropriately to blood pCO2, temperature, blood flow, drug concentrations, and electrical stimulation of vagal afferent fibers. This preparation represents a significant advance in the ability to preserve neural function during perfusion, and should offer advantages for studying cellular electrophysiology of intact, functioning neural networks, as well as neurochemistry and neuropharmacology.
Richerson
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GB
Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City 52242.
Getting
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D000818:Animals; D001921:Brain / Q000502:physiology*; D002021:Buffers; D004569:Electroencephalography; D006168:Guinea Pigs; D010424:Pentobarbital / Q000494:pharmacology; D010477:Perfusion / Q000379:methods*; D012119:Respiration / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*
D002021:Buffers; D010424:Pentobarbital