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 ... -  《-》

Chlorogenic acid exerts neuroprotective effect against hypoxia-ischemia brain injury in neonatal rats by activating Sirt1 to regulate the Nrf2-NF-κB signaling pathway.

Neonatal hypoxic-ischemic brain injury (HIE) is caused by perinatal asphyxia, which is associated with various confounding factors. Although studies on the pathogenesis and treatment of HIE have matured, sub-hypothermia is the only clinical treatment available for HIE. Previous evidence indicates that chlorogenic acid (CGA) exerts a potential neuroprotective effect on brain injury. However, the role of CGA on neonatal HI brain damage and the exact mechanism remains elusive. Here, we investigate the effects of CGA on HI models in vivo and in vitro and explore the underlying mechanism. In the in vivo experiment, we ligated the left common carotid artery of 7-day-old rats and placed the rats in a hypoxic box for 2 h. We did not ligate the common carotid artery of the pups in the sham group since they did not have hypoxia. Brain atrophy and infarct size were evaluated by Nissl staining, HE staining and 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining. Morris Water Maze test (MWM) was used to evaluate neurobehavioral disorders. Western-blotting and immunofluorescence were used to detect the cell signaling pathway. Malondialdehyde (MDA) content test, catalase (CAT) activity detection and Elisa Assay was used to detect levels of inflammation and oxidative stress. in vitro experiments were performed on isolated primary neurons. In our study, pretreatment with CGA significantly decreased the infarct volume of neonatal rats after HI, alleviated brain edema, and improved tissue structure in vivo. Moreover, we used the Morris water maze to verify CGA's effects on enhancing the learning and cognitive ability and helping to maintain the long-term spatial memory after HI injury. However, Sirt1 inhibitor EX-527 partially reversed these therapeutic effects. CGA pretreatment inhibited neuronal apoptosis induced by HI by reducing inflammation and oxidative stress. The findings suggest that CGA potentially activates Sirt1 to regulate the Nrf2-NF-κB signaling pathway by forming complexes thereby protecting primary neurons from oxygen-glucose deprivation (OGD) damage. Also, CGA treatment significantly suppresses HI-induced proliferation of glial. Collectively, this study uncovered the underlying mechanism of CGA on neonatal HI brain damage. CGA holds promise as an effective neuroprotective agent to promote neonatal brain recovery from HI-induced injury. Video Abstract.

Zheng Y ，Li L ，Chen B ，Fang Y ，Lin W ，Zhang T ，Feng X ，Tao X ，Wu Y ，Fu X ，Lin Z ... -  《Cell Communication and Signaling》

Lipoxin A4 Methyl Ester Reduces Early Brain Injury by Inhibition of the Nuclear Factor Kappa B (NF-κB)-Dependent Matrix Metallopeptidase 9 (MMP-9) Pathway in a Rat Model of Intracerebral Hemorrhage.

Song Y ，Yang Y ，Cui Y ，Gao J ，Wang K ，Cui J ... -  《MEDICAL SCIENCE MONITOR》

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 ... -  《-》

Indole-3-propionic Acid Attenuates HI-Related Blood-Brain Barrier Injury in Neonatal Rats by Modulating the PXR Signaling Pathway.

Zhao Q ，Chen T ，Ni C ，Hu Y ，Nan Y ，Lin W ，Liu Y ，Zheng F ，Shi X ，Lin Z ，Zhu J ，Lin Z ... -  《ACS Chemical Neuroscience》