TY - JOUR
T1 - Clinical and electrophysiological characteristics of the experimental neuropathy caused by p-bromophenylacetylurea
AU - Jakobsen, J.
AU - Lambert, E. H.
AU - Carlson, G.
AU - Brimijoin, S.
N1 - Funding Information:
Abbreviations: BPAU-p-bromophenylacetylurea, DMSO-dimethyl tensor digitorum longus, MEPP-miniature end-plate potential. ’ This research was carried out in the Mayo Peripheral Nerve Disease Research Center and was supported in part by the Mayo foundation and by grant NS 14304 from the National Institutes of Health. J.J. was supported by a fellowship from the University of Aarhus and by grant 512-20337 from the Danish Medical Research Council. S.B. was a recipient of Research Career Development Award NS 00119 from the National Institutes of Health. We thank Ngoc ngan Nguyen for expert assistance with the synthesis of p-bromophenylacetylurea.
PY - 1982/1
Y1 - 1982/1
N2 - Doses of p-bromophenylacetylurea (BPAU) ranging from 50 to 400 mg/kg were administered i.p., in dimethyl sulfoxide, to adult male Sprague-Dawley rats. Age- and weight-matched control rats were treated with equivalent volumes of solvent. After a latent period of 7 days, the test rats developed signs of peripheral neuropathy. The signs were dose related and ranged from modest hind limb weakness to total hind limb paralysis. The forelimbs were affected only by the highest dosage. Even in severely disabled rats there was no statistically significant decrease in the conduction velocity or amplitude of action potentials evoked in tail nerve. However, the maximum amplitude of potentials evoked in the anterior tibial muscles by in vivo stimulation of the sciatic nerve decreased to less than half of normal by 15 days after treatment with BPAU, 200 mg/kg. Muscle action potentials remained depressed for at least 60 days after treatment. The decrease in amplitude of the compound muscle action potential was strongly correlated with the clinically scored degree of disability (r = -0.82). Direct muscle toxicity was discounted because in vitro studies of the extensor digitorum longus showed a response to direct electrical stimulation even when miniature end-plate potentials and end-plate potentials were absent. The clinical observations and electrophysiologic findings are consistent with the conclusion that the distal extremities of the longest neurons are the primary locus of pathology in BPAU neuropathy.
AB - Doses of p-bromophenylacetylurea (BPAU) ranging from 50 to 400 mg/kg were administered i.p., in dimethyl sulfoxide, to adult male Sprague-Dawley rats. Age- and weight-matched control rats were treated with equivalent volumes of solvent. After a latent period of 7 days, the test rats developed signs of peripheral neuropathy. The signs were dose related and ranged from modest hind limb weakness to total hind limb paralysis. The forelimbs were affected only by the highest dosage. Even in severely disabled rats there was no statistically significant decrease in the conduction velocity or amplitude of action potentials evoked in tail nerve. However, the maximum amplitude of potentials evoked in the anterior tibial muscles by in vivo stimulation of the sciatic nerve decreased to less than half of normal by 15 days after treatment with BPAU, 200 mg/kg. Muscle action potentials remained depressed for at least 60 days after treatment. The decrease in amplitude of the compound muscle action potential was strongly correlated with the clinically scored degree of disability (r = -0.82). Direct muscle toxicity was discounted because in vitro studies of the extensor digitorum longus showed a response to direct electrical stimulation even when miniature end-plate potentials and end-plate potentials were absent. The clinical observations and electrophysiologic findings are consistent with the conclusion that the distal extremities of the longest neurons are the primary locus of pathology in BPAU neuropathy.
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U2 - 10.1016/0014-4886(82)90015-2
DO - 10.1016/0014-4886(82)90015-2
M3 - Article
C2 - 6174359
AN - SCOPUS:0020041135
SN - 0014-4886
VL - 75
SP - 158
EP - 172
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -