Intraspinal distribution and reaction in the grey matter with tetanus toxin of intracisternally injected anti-tetanus toxoid F(ab')2 fragments.

Anti-tetanus toxoid F(ab')2 fragments were purified using immune-affinity chromatography on tetanus toxoid-Sepharose. Fragments were labeled with 125I. Labeled or non-labeled fragments were injected into the intrathecal space of rats. The labeled fragments were found in the spinal cord outside but not inside neurons. Tetanus toxin was injected into a muscle and 36 h later labeled fragments were injected intracisternally. After another 24 h the label was elevated in the spinal cord half segments giving neural supply to the injected muscle and in these half-segments the label was concentrated around some alpha-motoneurons. [125I]Tetanus toxin was injected into a muscle and at different times thereafter non-labeled fragments were injected intracisternally. The development of hindlimb rigidity but not the accumulation of [125I]tetanus toxin in alpha-motoneurons was prevented by early intracisternal injection of fragments. Injection of fragments after the appearance of hindlimb rigidity did not revert the rigidity but prevented the further development of symptoms. It is concluded that an action of tetanus toxin inside alpha-motoneurons is of no importance for the development of motor symptoms in clinical tetanus. The data suggest that in order to evoke spinal symptoms of toxicity tetanus toxin has to reach interneurons by transneuronal migration. In the very early stages of clinical tetanus the intrathecal injection of fragments may be useful.