THE .HE SYNDROMES that may result from a great excess or deficiency of thyroid hormone in man, thyroid storm,1 and myxedema coma,2 are both characterized neurologically by apathy, somnolence, psychosis, confusion, and, ultimately, coma\p=m-\ clinical expressions of profound alterations in cerebral function. The pathophysiology of these metabolic encephalopathies is poorly understood and, though nonspecific atrophic changes have been described in adult hypothyroid brains,3 these are inconsistent ; no definite lesions have been observed in hyperthyroid brain.4 Although brain oxygen consumption has been shown to be diminished in human myxedema,5 it is normal in thyrotoxicosis.6 This study was undertaken, then, to elucidate thyroidal effects upon brain function. Myxedema and thyrotoxicosis were simulated in rats by thyroidectomy and thyroxine intoxication; brain permeability, composition and electrolyte metabolism were studied using sucrose 14C, sulfate 35S, sodium 24 and potassium 42.
MethodsAdult male Sherman rats were used in all experiments. The following isotopically labeled com¬ pounds were obtained from the New England Nuclear Co., Boston : universally labeled sucrose "C (specific activity, 360/ic/mM), sodium sulfatê S (specific activity, 165y¿c/mM), and, from Iso-Serve, Boston, sodium chloride 2iNa (specific ac¬ tivity, 1560/íc/gm Na), and potassium chloridê K (specific activity, 184/ic/gm). Rats were assumed to be hyperthyroid after re¬ ceiving 10 intraperitoneal injections of L-thyroxine, 40/ig/100 gm body weight, over an 11-day period. Hypothyroid rats were produced by thyroidectomy, 6 to 12 weeks elapsing prior to study. The para¬ thyroid glands were not preserved ; therefore, rats operated upon were given 200 units of vitamin D p.o., b.i.w. and 0.5% calcium lactate-tap water solution was used as drinking water. At the time the animal was killed, the plasma calcium level of this population, 4.75±0.5 (SD) mEq/liter,8 did not differ significantly from the controls, 5.1 ±0.4 (SD) mEq/liter.' All injections of isotopes were made intraperitoneally in 1-ml volumes (excluding the microflow pump experiments, vi). Constant blood levels of sucrose 14C and sulfate^S were maintained by nephrectomizing the animals prior to injection of isotope for experiments up to six hours in duration. However, because the chemical changes of uremia, ie, azotemia, become manifest beyond this time period in the nephrectomized rat,' a microflow pump syringe (Sage Instrument Co White Plains, NY) was used to maintain relatively constant blood levels of isotope for periods up to 48 hours. This device is a glass Luer-Lok syringe (Fig 1) to which is tightly fitted a battery case with electrodes that protrude into the hollow piston within the syringe. The piston is filled with a hydrazine solu¬ tion which emits nitrogen and hydrogen when electrolyzed, thus forcing the piston down, emitting the isotopie solution from the syringe at a linear rate proportional to the rate of electrolysis in the piston. -Electrode -Gosket _Flow Rate Setter e (R...