Neuroprotective effect of Vanillin on hypoxic-ischemic brain damage in neonatal rats.

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.

Lan XB ，Wang Q ，Yang JM ，Ma L ，Zhang WJ ，Zheng P ，Sun T ，Niu JG ，Liu N ，Yu JQ ... -  《-》

Neuroprotective Effect of Chitosan Oligosaccharide on Hypoxic-Ischemic Brain Damage in Neonatal Rats.

Wu W ，Wei W ，Lu M ，Zhu X ，Liu N ，Niu Y ，Sun T ，Li Y ，Yu J ... -  《-》

Matrix metalloproteinases inhibition provides neuroprotection against hypoxia-ischemia in the developing brain.

Chen W ，Hartman R ，Ayer R ，Marcantonio S ，Kamper J ，Tang J ，Zhang JH ... -  《-》

LXA4 protects against hypoxic-ischemic damage in neonatal rats by reducing the inflammatory response via the IκB/NF-κB pathway.

Hypoxia and the resultant decreases in cerebral blood flow in the perinatal period can lead to neonatal hypoxic-ischemic (HI) brain injury, which can, in turn, cause severe disability or even death. However, the efficacy of current treatment strategies remains limited. Several studies have demonstrated that lipoxin A4 (LXA4), as one of the earliest types of endogenous lipid mediators, can inhibit the accumulation of neutrophils, arrest inflammation, and promote the resolution of inflammation. However, research on LXA4 in the nervous system has rarely been carried out. In the present study, we sought to investigate the protective effect of LXA4 on HI brain damage in neonatal rats, as well as the underlying mechanisms. Through experiments conducted using an HI animal model, we found that the LXA4 intervention promoted the recovery of neuronal function and tissue structure following brain injury while maintaining the integrity of the blood-brain barrier in addition to reducing cerebral edema, infarct volume, and inflammatory responses. Our results suggest that LXA4 interfered with neuronal oxygen-glucose deprivation insults, reduced the expression of inflammatory factors, inhibited apoptosis, and promoted neuronal survival in vitro. Finally, the LXA4 intervention attenuated HI-induced activation of inhibitor kappa B (IκB) and degradation of nuclear factor-κB (NF-κB). In conclusion, our data suggest that LXA4 exerts a neuroprotective effect against neonatal HI brain damage through the IκB/NF-κB pathway. Our findings will help inform future studies regarding the effects of LXA4 on neuroinflammation, blood-brain barrier integrity, and neuronal apoptosis.

Zhu JJ ，Yu BY ，Fu CC ，He MZ ，Zhu JH ，Chen BW ，Zheng YH ，Chen SQ ，Fu XQ ，Li PJ ，Lin ZL ... -  《-》

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.

Wei W ，Lu M ，Lan X ，Liu N ，Wang H ，Du J ，Sun T ，Li Y ，Yu J ... -  《-》