It is extremely difficult to determine with any degree of precision the nature of the lesions produced by venoms in the nervous system. The intensity of these lesions depends in the first place upon the length of time that has elapsed between the introduction of the venom into the organism and death. It depends, secondarily, in a large measure, upon the origin of the venom. That of the Viperidæ acts almost exclusively upon the blood by coagulation, and exhibits only a very slight degree of toxicity as regards the nerve-cell. That of the Colubridæ, on the contrary, produces manifest changes in the chromatic substance. Nissl’s bodies are completely disintegrated, and transformed into a granular mass. In the majority of the stichochromes neither the form of the bodies nor even the reticulum is distinguishable. The nuclei are opaque, the nucleoli swollen and broken up. The dendrites often become irregular and contracted (Ewing and Bailey,[25] G. Lamb[26]).
It was found by Bailey that the majority of the cells of the anterior cornua of the medulla are normal, but that a small number of them exhibit indications of acute granular degeneration; a few cells were found to have lost almost all their chromatic substance.
From the physiological point of view it is perfectly clear that Cobra-venom especially affects the bulbar centres, and particularly the nuclei of origin of the pneumogastric nerve. We observe in the first instance the gradual suppression of the functions vested in the nerve-cells that are found in connection with the vagus nerve, the spinal accessory, and the hypoglossal. Later on the excitability of the nerve-endings in the muscles is found to have been destroyed, and this action presents great similarity to that of curare.
The venoms of Viperidæ, when injected in very weak doses, exercise a paralysing action upon the reflex excitability of the medulla. But it is open to question whether these effects are not exclusively due to the lesions of the blood, which are here all-predominant; for no histological modification is observed in the cells of the central nervous system.
I have made a number of experiments with a view to discovering whether the cerebral, bulbar, or medullary substance of animals susceptible to the action of Cobra-venom (rabbit, guinea-pig, fowl) possesses the property of fixing this venom as it fixes the toxin of tetanus (Wassermann and Takaki). I found that, on pounding up a little of the pulp of the cerebral hemispheres or bulb with doses of venom lethal in two hours for the control animals, the injection of the mixture, well washed and centrifuged in order to free it from all excess of non-fixed venom, always caused death, but with a retardation of from four to ten hours. We see, therefore, that partial fixation of the venom upon the nervous elements really takes place, but we cannot conclude from this that these elements exercise an antitoxic function, any more than in the case of tetanus, for animals that receive cerebral emulsions in one thigh and the dose of venom lethal in two hours in the other thigh, succumb at the same time as the controls.
Major Rogers has made similar experiments with the venom of Enhydrina (Hydrophiidæ), and has obtained the same result on employing the cerebral hemispheres of the pigeon.[27]
Flexner and Noguchi,[28] on their part, have compared, by aid of the method of intra-cerebral injections, the toxicity of the venom of Crotalus with that of the venom of the Cobra. On employing Cobra-venom heated to 75° C., they found that the convulsive and paralytic effects were immediate, contrary to what takes place after subcutaneous or intraperitoneal injections, but that the dose of venom necessary to produce death was the same (0·1 milligramme for the guinea-pig) as when the injection is made in the peritoneum or beneath the skin.
With the venom of Crotalus heated for half an hour at 75° C., which contains but very little neurotoxin and has lost all its hæmorrhagic properties, 0·5 milligramme introduced directly into the brain of the guinea-pig only produces transitory and non-lethal effects; while, if fresh venom be employed, 0·05 milligramme is sufficient to cause death in three hours, with severe hæmorrhagic lesions. Now this dose is twenty times smaller than the minimal lethal dose for a subcutaneous injection.
It is evident that the harmful matter, in the particular case of Crotalus-venom, is not the neurotoxin, but an altogether different substance, termed by Flexner and Noguchi hæmorrhagin, which acts upon the elements of the blood and upon the endothelium of the blood-vessels.
We shall meet with this substance again in almost all Viperine venoms, and shall study it further on.