Factors Associated With Diabetic Neuropathy In Rats: A Systematic Review With Metanalysis

  • Nádia Nara Rolim Lima
  • Carlos Augusto Carvalho de Vasconcelos
  • Danilo Ferreira de Sousa
  • Dayse Christina Rodrigues Pereira Luz
  • José Luiz de Lima Filho
  • Luiz Carlos Alves
  • Fábio André Brayner dos Santos
  • Amanda Duarte de Moraes
  • Dayanna Mayara Moreira de Alencar
  • Marcelo Moraes Valença


Diabetic neuropathy refers to a group of symptoms associated with the nerve’s damaged ability to perform its functions correctly. Symptoms may vary from paresis to pains that mainly affect sensitive or motor long nerves of feet and hands. Hence, experiments and analysis carried out with rodents, especially rats, allow several clinical interfaces to be known. Therefore, the aim of this study was to analyze the factors associated with diabetic neuropathy in rats. This is a systematic review with metanalysis. Data collection followed some prior
election criteria. The sources of information for the researched data are the databases MEDLINE/PubMed and Scopus. The research was conducted using the keywords found in descriptors/MeSH: rats, diabetic neuropathies, and risk factors with the Boolean operator “AND”.

The BioEstat 5.3 was used for statistical analysis, and the Odds Ratio was calculated with a 95% confidence interval (CI). Eighty-three references were found, of which 17 followed the criteria and were then included in the present review. Some factors like nerve morphology, blood hypertension, oxidative stress, diabetes period, hypoglycemic effect, vascular complications, and insulin parameters represent the main risk factors for the development of diabetic neuropathy, as well as diabetes induction in rats by using drugs. Such factors are very
similar to those from humans, thus requiring a deeper analysis of the theme in a considerable human sample.


1. Peng, L., Liu, W., Zhai, F., He, L. & Wang, H. Microvessel permeability correlates with diabetic peripheral neuropathy in early stage of streptozotocin-induced diabetes rats. J. Diabetes Complications 29, 865–71
2. Ozaki, K., Hamano, H., Matsuura, T. & Narama, I. Effect of deoxycorticosterone acetate-salt-induced hypertension on diabetic peripheral neuropathy in alloxan-induced diabetic WBN/Kob rats. J. Toxicol. Pathol. 29, 1–6 (2016).
3. Zhao, B. et al. Diabetes-induced central neuritic dystrophy and cognitive deficits are associated with the formation of oligomeric reticulon-3 via oxidative stress. J. Biol. Chem. 288, 15590–9 (2013).
4. Afifi, N. M. Neuroprotective effect of melatonin in a rat model of streptozotocin-induced diabetic neuropathy. Egypt. J. Histol. 36, 321–335 (2013).
5. Fazan VPS, Vasconcelos CAC de, Valença MM, Nessler R, M. K. Diabetic peripheral neuropathies: A morphometric overview. Int J Morphol 28, 51–64 (2010).
6. Vasconcelos, C.A.C. de; Fazan, V.P.S.; Moore, K.C.; Nessler, R.A.; Valença, M. M. Transmission Electron Microscopy Studies of the Vestibulocochlear Nerve in Chronic Diabetic Rats. Int. J. Morphol. 29, 272–277 (2011).
7. Vasconcelos, CAC, Rolim-Neto, M. L. NEUROCIÊNCIA E DESENVOLVIMENTO HUMANO: O INFINITO NÃO ACABA JAMAIS. Neurosci. Hum. Dev.: Infin. Never Ends 1, 528 (2014).
8. Lee, K. A. et al. Effect of granulocyte colony-stimulating factor on the peripheral nerves in streptozotocin-induced diabetic rat. Diabetes Metab. J. 37, 286–90 (2013).
9. Bakovic, M. et al. Changes in cardiac innervation during maturation in long-term diabetes. Exp. Gerontol. 48, 1473–8 (2013).
10. Nithya, S. & Ray, S. Effect of granisetron on experimental model of diabetes induced neuropathic pain perception in rats. 6, 483–486 (2014).
11. Kara, A. et al. Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study. Gynecol. Endocrinol. 30, 226–31 (2014).
12. Moher D, Liberati A, Tetzlaff J, A. D. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6, (2009).
13. Downs SH, B. N. The feasibility of creating a checklist forthe assessment of the methodological quality both of randomi-sed and non-randomised studies of health care interventions. J Epidemiol Community Heal. (1998).
14. Sanada, L. S. et al. Association of chronic diabetes and hypertension in sural nerve morphometry: an experimental study. Diabetol. Metab. Syndr. 7, 9 (2015).
15. Vargas, R. et al. Role of angiotensin II in the brain inflammatory events during experimental diabetes in rats. Brain Res. 1453, 64–76 (2012).
16. Gregory, J. A., Jolivalt, C. G., Goor, J., Mizisin, A. P. & Calcutt, N. A. Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats. Acta Neuropathol. 124, 561–73 (2012).
17. Lirk, P. et al. In Zucker diabetic fatty rats, subclinical diabetic neuropathy increases in vivo lidocaine block duration but not in vitro neurotoxicity. Reg. Anesth. Pain Med. 37, 601–6
18. Kroin, J. S., Buvanendran, A., Tuman, K. J. & Kerns, J. M. Effect of acute versus continuous glycemic control on duration of local anesthetic sciatic nerve block in diabetic rats. Reg. Anesth. Pain Med. 37, 595–600
19. Kim, H. et al. Bone marrow mononuclear cells have neurovascular tropism and improve diabetic neuropathy. Stem Cells 27, 1686–96 (2009).
20. Zimering, M. B., Alder, J., Pan, Z. & Donnelly, R. J. Anti-endothelial and anti-neuronal effects from auto-antibodies in subsets of adult diabetes having a cluster of microvascular complications. Diabetes Res. Clin. Pract. 93, 95–105 (2011).
21. Ishii, D. N. Implication of insulin-like growth factors in the pathogenesis of diabetic neuropathy. Brain Res Brain Res Rev 20, (1995).
22. Nitta, A. et al. Diabetic neuropathies in brain are induced by deficiency of BDNF. Neurotoxicol Teratol 24, (2002).
How to Cite
ROLIM LIMA, Nádia Nara et al. Factors Associated With Diabetic Neuropathy In Rats: A Systematic Review With Metanalysis. International Archives of Medicine, [S.l.], v. 10, mar. 2017. ISSN 1755-7682. Available at: <http://imedicalsociety.org/ojs/index.php/iam/article/view/2449>. Date accessed: 26 june 2019. doi: https://doi.org/10.3823/2371.