Motor dysfunction at 4 weeks in streptozotocin-induced diabetic animals

AimsDiabetic neuropathy is still a severe and common consequence for diabetic patients. The impact of neuropathy emphasizes the need to study its biology in order to treat patients early. The limitations of preclinical neuropathy models to date demand in vivo models that combine early nerve dysfunction detection with low mortality. Streptozotocin is commonly used to cause diabetes in rodents, but conventional high dose design often results in high mortality rates. In this study, I present a secondary analysis of a neuropathy primary model [8], focusing on the 4-week timepoint and validating proximal motor dysfunction in a short timeframe with high survival using F-wave metrics as early biomarkers. MethodsMale Wistar rats received low-dose STZ (30 mg/kg) on alternate days for one week (three injections) or vehicle. At baseline and 4-week, I analyzed blood glucose and body weight, and electrophysiological recordings (M-/F-waves) were performed at endpoint. ResultsRats treated with STZ had significant body weight loss (p < 0.001) and hyperglycemia greater than (20 mmol/L), which was aligned with a negative correlation (Pearson r = -0.77, p = 0.003). Furthermore, in diabetic animals, electrophysiology displayed that M-waves were unchanged, whereas F-waves were absent (p < 0.0001). Moreover, 91.7% of the animals were still alive at the end of the study, indicating a high level of survival. ConclusionsThe new approach of this secondary study resulted in development of neuropathy at 4 weeks, accompanied by high survival, which in turn validates F-waves as an early biomarker of nerve dysfunction within a short timeframe. Thus, this new work provides an early and reliable platform for testing neuroprotective drugs and mechanistic work in the short term.