Mechanism of the Therapeutic Effect of Metrazol and Insulin Convulsions. ∗

Abstract

Anoxemia has been regarded as a common factor in the effects of insulin and metrazol convulsions, in that hypoglycemia diminishes the oxygen utilization of brain tissue (Holmes, 1 Wortis 2 ), while the metrazol convulsions interfere with the respiratory movements (Himwich 3 and coworkers). Anoxemia may act by stimulating the sympathetic system (Gellhorn 4 ), it may, however, affect the brain cells directly by increasing the permeability of the cellular surface films (Spiegel and Spiegel-Adolf 5 ). The question may, therefore, be raised whether insulin and metrazol convulsions change the permeability of the cells of the central nervous system.

In 10 guinea pigs metrazol convulsions were produced (2 cc metrazolt intraperitoneally), in 10 others insulin convulsions (20-40 units of insulin). The brains of 3 guinea pigs were studied after the animals had received insulin, but before the onset of convulsions, while the measurements on 10 further animals served as normal controls. Part of the animals were killed by decapitation during the convulsions (minimal duration of the convulsions 5 minutes), in the remainder the convulsions or the insulin “shock” were allowed to continue until the spontaneous death of the animal. The polarizability and thus indirectly the permeability of the cell surfaces was determined 5-10 minutes postmortem by measuring the conductivity at high (C_h) and at low frequencies (C_i) on the exposed cerebral hemispheres at 37 °C temperature and calculating the polarization index Δ = 100(C_h-C₂)/C₂ (Spiegel and Spiegel-Adolf 5 ). The frequencies used in this study were 5120 and 547 respectively. In some animals the brain was used for histological studies after the measurements; besides, the brains of animals subjected to metrazol or insulin convulsions as described above, were histologically studied without being altered by the electrical measurement.