A slowly changing bioelectric potential difference (P.D.) is measured in rats, rabbits, cats and dogs between various regions of the central nervous system (CNS) and the blood within the jugular vein. It is shown that the CNS-blood P.D. is very sensitive to alterations in alveolar CO2 tension, but this relationship is dependent upon the H+ concentration rather than CO2 per se. Whereas increasing intravenous H+ concentration increases CNS positivity, topical application of acid solutions directly to the cerebral cortex decreases CNS positivity. The same relationship is found for intravenous and topical K+. Anoxia and circulatory failure produce CNS negative deflections, often exceeding 15 mv, which do not return to zero for over 24 hours after death. Simultaneous measurements of arterial blood pH, cerebral cortex pH and CNS-blood P.D. reveal the following relationship among these variables: ΔP.D. = κ Δ log10 [H+]a/[H+]i where [H+]a is the H+ concentration of the arterial blood and [H+]i is the H+ concentration of the CNS interstitial fluid. For the CNS-blood P.D. between cerebral cortex and jugular blood of rabbits and rats, κ is found to be 29 ± 5. These results are interpreted as indicating a source of emf across the pan-vascular blood-brain barrier which resembles a membrane diffusion potential. The blood-brain barrier is postulated to be more permeable to H+ and K+ than to anions and other cations.

In view of the reported influence of 2-acetylamino-l,3,4,-thiadiazole-5-sulfonamide (Diamox) on formation of intraocular fluid( l ) , and the similarity between intraocular and cerebrospinal fluid (CSlF) systems, a series of experiments has been undertaken to determine the effect of this compound on CSF formation and intracranial pressure. In every instance, at least a 3-fold reduction in rate of CSF flow, or a decline of approximately 30% in intracranial pressure was observed following intravenous administration of 150 mg/kg soluble Diamoxt (acetazoleamide-sodium) .Cats and rabbits lightly anesthetized with sodium pentobarbital were placed on their sides with heads inclined slightly upwards from the horizontal. To measure CSF flow, a 22-gauge spinal needle was introduced into the cisterna magna and the rate at which drops of CSF appeared was recorded. The volume of each drop was found to be 0.04 cc. The CSF was collected in successive samples for periods of 15 minutes, or until sufficient fluid had accumulated for analysis of sodium, potassium and calcium in the flame spectrophotometer. In other ani- Materials and methods.

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Local changes in cerebral cortex hydrogen ion concentration of as much as 0.5 ph units were observed to accompany the waves of cortical spreading depression or convulsion in cats and rabbits. A diphasic wave consisting of an initial alkaline followed by a more prolonged acid shift was observed in most cases. No significant differences were found between the ph changes accompanying spreading depression and those accompanying spreading convulsion. These ph shifts, like the abnormal ECG activity and the slowly changing potential wave which accompanied them, spread over the surface of the cerebral cortex with a velocity of 1–3 mm/min. The curve of cortical ph change is coincident with, and similar in shape to, the slowly changing potential difference measured between a point on the cortical surface and the jugular blood. For every unit change in ph, the cortex-blood P.D. is shifted approximately 30 mv. It is suggested that the slowly changing potential difference arises across the blood-brain barrier rather than as a result of depolarization of neuronal membranes. A significant but variable change in local blood flow accompanied the spreading depression.

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