Neuroprotective effect of Verbascoside on hypoxic-ischemic brain damage in neonatal rat

Hypoxic-ischemic brain damage (HIBD) leads to acute death and chronic neurological dysfunction in neonates. To date, there is no satisfactory acknowledged strategy to provide neuroprotection completely. Verbascoside (VB) has been proved to possess antioxidative, anti aging and neuroprotective activities. The aim of this study was to investigate whether VB provides neuroprotection to neonatal HIBD. Seven-day-old Sprague-Dawley rats were subjected to HIBD by permanent left carotid ligation for 2.5 h at 37 °C under hypoxic stress (8% O₂, 92% N₂). After VB treatment, early neurofunctions were assessed using the righting reflex and negative geotaxis reflex. 2, 3, 5-Triphenyltetrazolium chloride, Hematoxylin-Eosin, Nissl, and Fluoro-Jade B staining were used to evaluate the extent of brain damage. In addition, autophagy was observed by transmission electron microscopy, and the expression of autophagy-related proteins was measured using immunofluorescence and Western blot analysis. Results showed that administration of VB remarkably reduced neurofunctional latency, brain infarct volume, ameliorated neuronal damage and degeneration. Furthermore, VB decreased autophagosome formation, the Beclin-1 levels and LC3-II/I ratio with elevated levels of P62 in HIBD neonatal rats when compared to the HI group. These findings suggest that VB exerts potential neuroprotective effect against HIBD, which is at least partly to be mediated regulating autophagy.