Distribution of ¹²⁵I-tetanus toxin and ¹²⁵I-toxoid in rats with generalized tetanus, as influenced by antitoxin

Summary

In order to understand the symptomatology of generalized tetanus from the pharmacokinetics of the toxin, ¹²⁵I-labelled toxin was injected i.v. in rats without and with antitoxin.

• 1. After a few hours latency, brain stem and spinal cord concentrate radioactive material up to the third day. The decline of radioactivity is very slow, semilogarithmic, and can be followed up to the 24th day after injection. In contrast, forebrain and cerebellum do not bind measurable radioactivity. Less than 1% of the radioactivity injected is found in the CNS.

• 2. The symptoms of tetanus start some time after the bulk of labelled toxin has been taken up by the CNS. They cease before all radioactivity has left it.

• 3. Antitoxin, given simultaneously, prevents the onset of symptoms and the uptake of radioactivity by the CNS. When given 10 h after labelled toxin, it nearly abolishes the fixation and still prevents the onset of symptoms. When given 48 h after toxin, it is nearly ineffective in both respects. Antitoxin first delays, then enhances the elimination of labelled toxin from the blood.

• 4. Labelled antitoxin is not enriched in the CNS.

• 5. The uptake of radioactivity into various parts of spinal cord corresponds well to their relative content in grey matter.

• 6. The pharmacokinetic behaviour of ¹²⁵I-toxoid resembles that of toxin. However, in order to get measurable fixation to the CNS at least 50 times higher amounts are to be applied.

It is concluded that the barrier between blood and CNS is practically impermeable to tetanus toxin. The results can be harmonized best with the assumption that generalized tetanus is nothing else than a multiple local tetanus.