Methodological approaches to the assessment of paralytic syndrome of toxic genesis in experiments on rodents

N.S. Ilinskiy,   deputy head of the department of the State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation. ORCID: 0000-0001-7406-753X
M.A. Tyunin, head of department of the State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation., ORCID: 0000-0002-6974-5583.
M.O. Matrosova, Junior Research Fellow. ORCID: 0000-0002-1395-823X

State Scientific Research Testing Institute of Military Medicine, Ministry of Defense of Russian Federation
195043, Russian Federation, Saint Petersburg, Lesoparkovaya Str., 4

Abstract

Pharmacological safety requirements dictate the need to perform an experimental assessment of the potential neurotoxic effects of drugs under development. At the same time, the need for experimental modeling of diseases of the peripheral nervous system for studying their pathogenesis and developing new approaches to therapy has been preserved. Currently, a wide range of clinical and functional tests has been introduced into practice, allowing to identify many types of neurological deficits. However, some terminological and methodological discrepancies remain between clinical and experimental practice. All this determines the high relevance of studies to improve methods for assessing the neurotoxic effects of xenobiotics in experiments on laboratory rodents.

The aim this study – compare the information content of the study of the physiological motor reflex in rats using the finger abduction scale with other recommended methods for assessing peripheral paresis.

A complex clinical and instrumental study was carried out to dynamically assess the neurological status of male outbred rats using a model of toxic tetraparesis caused by subcutaneous administration of tetrodotoxin at a dose of LD16. The introduction of tetrodotoxin is capable of stably and with high repeatability causing a kind of motor deficiency syndrome (peripheral paresis) in experimental animals due to the neural and muscle components. External manifestations of intoxication in rats were assessed using the pull-up test on the bar, Rotarod, and the digit abduction scale. In order to verify violations of the processes of neural conduction and neuromuscular transmission, the animals underwent electroneuromyography and decrement-test.

The results of the study demonstrated that the currently generally accepted methodological apparatus for the experimental assessment of neurological status is capable of detecting motor dysfunctions in rats if they are sufficiently pronounced, when, according to neurophysiological research, gross changes in the main parameters are already present. When comparing the rate of onset and severity of external signs of intoxication, it was found that the assessment of the physiological motor reflex using the finger abduction scale has a sufficiently high information content and ease of testing, making it possible to identify early signs of peripheral paresis of toxic genesis.

Full text avaliable in Russain only 

Author’s Contribution

Ilyinskiy N. S. – deputy head of the department of the State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation. ORCID: 0000-0001-7406-753X 
Tyunin M. A.
– head of department of the State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation., Ph.D. ORCID: 0000-0002-6974-5583.
Matrosova M. O. – Junior Research Fellow. ORCID: 0000-0002-1395-823X

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. Руководство по проведению доклинических исследований лекарственных средств. Часть первая. – М.: Гриф и К. – 2012. – 944 c. [Rukovodstvo po doclinicheskim issledovaniyam lekarstvennyh sredstv [Preclinical drug research guide]. Moscow: Grif i K, 2012. – 944 p. (In Russ.)].
  2. Одинак М.М., Дыскин Д.Е. Клиническая диагностика в неврологии. – СПб.: СпецЛит. – 2007. – 710 с. [Odinak M.M., Dyskin D.E. Klinicheskaya diagnostika v nevrologii [Clinical diagnostic in neurology]. Saint-Petersburg: SpecLit, 2007:710. (In Russ.)].
  3. Broide R.S., Rubino J., Nicholson G.S. et al. The rat Digit Abduction Score (DAS) assay: a physiological model for assessing botulinum neurotoxin-induced skeletal muscle paralysis // Toxicon. – 2013. – Vol.71. – P. 18-24.
  4. Тюнин М.А., Ильинский Н.С., Матросова М.О. Диагностические возможности электромиографии при отравлениях фосфорорганическими соединениями // Medline.ru. – 2019. – 20(1). – С.254–260. [Tyunin M.A., Ilinskiy N.S., Matrosova M.O. Diagnosticheskie vozmozhnosti electromiografii pri otravleniyah fosfororganicheskimi soedineniyami [Diagnostic potential of electromyography in organophosphate poisoning]. Medline.ru. 2019. – 20 (1). – P. 254-260. (In Russ.)].

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