Simultaneous comparison of cerebral dialysis and push-pull perfusion in the brain of rats: a critical review

Over the last 30 years, studies of the in vivo activity of neurotransmitters and other endogenous factors in the brain have comprised a major effort in the neurosciences. Historically, the technology of push-pull perfusion was utilized as a major approach to investigations in this field. In the last 10 years, cerebral dialysis has been used as an alternative method essentially for the same scientific purpose, since the perfusion technique was viewed as difficult and excessively damaging to tissue. This review considers the representative literature in which both systems have been used to study local neurochemical responses to a drug or other chemical factor, a physiological condition or other situation. In addition, new experiments have been undertaken to compare, in the same animal and at the same time, the utility and properties inherent in the techniques of push-pull perfusion and cerebral dialysis in terms of the profile of a neurotransmitter activity and their local histopathological effects. A miniaturized 33/26 ga push-pull needle and a 24 ga dialysis probe were implanted simultaneously in the left and right caudate nuclei, respectively, in the anesthetized rat. An artificial cerebrospinal fluid (CSF) was perfused simultaneously through both devices at a rate of 10 microliters/min in the push-pull cannula and at 1.0 or 2.0 microliters/min in the dialysis probe. Within a series of 8-10 successive perfusions, excess K+ ions in a concentration of either 30 or 60 mM were incorporated in the CSF and delivered simultaneously to both the push-pull cannula and dialysis probe. Samples of perfusate and dialysate were assayed chromatographically by coulometric HPLC detector and quantitated in terms of the pg/min efflux of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The results showed that the resting level of DA was almost undetectable in dialysate samples from either structure; in push-pull perfusates the recovery of DA ranged between 7.0 to 10.0 pg/min, which was increased threefold by excess K+ ions. The recovery of DA and the three metabolites in samples of push-pull perfusate was two to four times that in samples of dialysate during the condition of excess K+ ions. Post-mortem histological analysis of the sites of perfusion and dialysis revealed little or no differences in the cytological damage induced by either the perfusion needle or dialysis probe. Finally, the advantages and limitations of each of these two experimental approaches to in vivo analysis of neurotransmitter efflux are reviewed in relation to the selection of an open or closed system for the on-line study of in vivo neurochemical events.