Neonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of death and perpetual neurological dysfunction in neonates.
Vanillin (Van), a natural phenolic compound with neuroprotective properties, exerts neuroprotection on a gerbil model of global
ischemia by inhibiting oxidative damage. This study aimed to explore the potential neuroprotective roles of Van in neonatal rats suffering from hypoxic-ischemic (HI). An HI model of 7-day-old SD rats was induced by left carotid artery
ligation followed by exposure to 8%
oxygen (balanced with
nitrogen) for 2.5 h at 37 °C. At 48 h after
intraperitoneal injection with Van (20, 40, and 80 mg/kg) or saline, neurobehavioral function, cerebral infract volume, brain water content, and histomorphological changes were performed to evaluate
brain injury. Transmission electron microscopy and
immunoglobulin G (
IgG) staining were conducted to evaluate the integrity of the blood-brain barrier (BBB). The levels of oxidative stress and
tight junction proteins, as well as the activities of
matrix metalloproteinases (
MMPs), were also determined in the ipsilateral hemisphere. Results showed that Van post-treatment significantly ameliorated early neurobehavioral deficits, decreased
infarct volume and
brain edema, as well as attenuated histopathologic injury and
IgG extravasation. Furthermore, Van markedly increased the activities of
endogenous antioxidant enzymes and decreased
malondialdehyde content. Meanwhile, the activation of MMP-2 and MMP-9 induced by HI was partially blocked by Van. Finally, Van obviously increased the expression of ZO-1,
Occludin, and
Claudin-5 compared with the HI group. Collectively, Van can provide
neuroprotective effects against neonatal HIBD possibly by attenuating oxidative damage and preserving BBB integrity.