Summary
The mechanisms of local tetanus or unilateral tetanus toxin induced paralysis due to intramuscular injections were studied in adult Wistar rats. Mouse bioassay methods, microdissection techniques, multiple toxin dosages (100; 600; 1000; 2500; and 6000 mouse minimum lethal doses per 100g rat's body weight); multiple sampling times (1, 6, 12, 18, 24 h after injection); and nerve transection were used. The toxin content of rat's blood and the epineurium, perineurium, and endoneurium of both sciatic nerve trunk was measured during the onset of local tetanus.
Both rat sciatic nerve trunks contained tetanus toxin at some interval after i.m. toxin injections, but only the injected extremity developed local tetanus (paralysis). Tetanus toxin was detected in rat sciatic nerve trunks and blood in the following sequence: injection site; ipsilateral epineurium; blood and ipsilateral perineurium; contralateral epineurium. The blood and the nerve segment closest to the injection site contained toxin for at least 24 h with the epineurium being the primary site of toxicity. Toxin was detectable in the contralateral nerve trunk (epineurium) only after being detected in the blood. Nerve transection did not appear to alter the toxin distribution from the injection site to the blood or epineurium from either extremity. This bilateral epineurial toxin distribution was however, time and dosage dependent.
The perineurium was the site of a dosage and time dependent unilateral toxin distribution. An ipsilateral, perineurial toxin gradient pattern, temporally related to the onset of local tetanus, was present. Ipsilateral nerve transection prevented the toxin gradient pattern, but not the uptake of toxin in the nerve segment below the level of transection. Dosage dependent peripheral nerve barriers (perineurialendoneurial; blood-vascular-endoneurial) appeared to prevent toxin from entering the endoneurial spaces. Above certain i.v. toxin dosage levels a bilateral endoneurial toxin distribution uniformly along the entire nerve trunk could be produced. These data show that tetanus toxin distribution is very complex, but local tetanus appears to be due to peripheral nerve toxin transport in the perineurial tissue spaces to the spinal cord.
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King, L.E., Fedinec, A.A. Pathogenesis of local tetanus in rats: Neural ascent of tetanus toxin. Naunyn-Schmiedeberg's Arch. Pharmacol. 281, 391–401 (1974). https://doi.org/10.1007/BF00499434
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DOI: https://doi.org/10.1007/BF00499434