Cerebral ischemia/reperfusion injury (CIRI) leads to injury in distant organs, most commonly the lungs, although limited studies have examined self‐protective mechanisms during CIRI‐induced lung injury. Here, we investigated self‐protective mechanisms that attenuate stress‐related injury and promote the angiogenetic repair of epithelial function during CIRI‐induced lung injury by measuring nuclear factor erythroid‐related factor 2 (Nrf2) and hypoxia‐inducible factor‐1α (HIF‐1α) levels. A CIRI model was established in male Sprague–Dawley rats by blocking the middle cerebral artery. Rats were divided into five subgroups based on the reperfusion time (6, 12, 24, 48, and 72 hr). Lung injury was assessed using a semiquantitative score and a thiobarbituric acid‐based method of determining malonaldehyde production. Lung tissue angiogenesis was detected by CD34 and CD31 immunolabeling. Changes in Nrf2, heme oxygenase‐1 (HO‐1), HIF‐1α, vascular‐endothelial growth factor (VEGF), phosphatidylinositol 3‐kinase (PI3K), extracellular‐regulated kinase1/2 (ERK1/2), and phospho‐ERK1/2 ( p‐ERK1/2) protein‐ and mRNA‐expression levels were measured by immunohistochemistry and reverse transcription polymerase chain reactions, respectively. Oxidative stress induced by cerebral ischemia/reperfusion (CI/R) caused lung injury. Expression of the Nrf2/HO‐1 antioxidative stress pathway in lung tissues increased following CI/R, peaking after 24 hr. PI3K, ERK, and p‐ERK1/2, which act upstream of Nrf2/HO‐1, were expressed at higher levels in the CI/R‐model group, consistent with the general trends observed for Nrf2/HO‐1. Within 72 hr post‐CI/R, HIF‐1α, and VEGF expression significantly increased versus the sham group. Thus, during CIRI‐induced lung injury, the body may upregulate antioxidative stress activities and promote angiogenesis to repair the endothelial barrier through the Nrf2/HO‐1 and HIF‐1α/VEGF signaling pathways, enabling self‐protection.

The objective of the paper is to evaluate the effect of acellular nerve allografts (ANA) seeded with Schwann cells to promote nerve regeneration after bridging the sciatic nerve defects of rats and to discuss its acting mechanisms. Schwann cells were isolated from neonatal Wistar rats. In vitro Schwann cells were microinjected into acellular nerve allografts and co-cultured. Twenty-four Wistar rats weighing 180-220 g were randomly divided into three groups with eight rats in each group: ANA seeded with Schwann cells (ANA + SCs), ANA group and autografts group. All the grafts were, respectively, served for bridging a 10-mm long surgically created sciatic nerve gap. Examinations of regeneration nerve were performed after 12 weeks by transmission electron microscope (TEM), scanning electron microscope (SEM), and electrophysiological methods, and then analyzed statistically. The results obtained indicated that in vitro Schwann cells displayed the feature of bipolar morphology with oval nuclei. Compared with ANA group, the conduction velocity of ANA + SCs group and autograft group was faster after 12 weeks, latent period was shorter, and wave amplitude was higher (P < 0.05). The difference between ANA + SCs group and autograft group is not significant (P > 0.05). Regeneration nerve myelinated fiber number, myelin sheath thickness, and myelinated fibers/total nerves (%) in both ANA + SCs group and autograft group are higher than that in ANA group; the difference is significant (P < 0.05). The difference between the former two is not significant (P > 0.05). In conclusion, ANA seeded with SCs could improve nerve regeneration and functional recovery after bridging the sciatic nerve gap of rats, which offers a novel approach for the repair peripheral nerve defect.

Objective: Ischemic stroke is known as a neurodegenerative disorder, which induces long-period tissue damage. Chemokine (C-X-C motif) ligand 8 (CXCL8) is involved in acute inflammation and tumor progression through the phosphoinositide-3-kinase/ protein kinase B/nuclear factor-κB (PI3K/Akt/NF-κB)-signaling pathway. In this study, we aimed to explore the mechanism of CXCL8 in ischemic stroke in relation to the PI3K/Akt/NF-κB-signaling pathway.Methods: Microarray-based gene expression profiling of peripheral blood mononuclear cells was used to identify ischemic stroke-related differentially expressed genes and explore role of CXCL8 in ischemic stroke. Next, the ischemic mice model was successfully established, with transfection efficiency detected. After that, deflection index, recovery of nervous system, infarct sizes, ischemia-induced apoptosis, and neuroinflammatory response in ischemic stroke were measured. At last, the content of inflammatory factors as well as the expression of CXCL8, caspase-3, caspase-9, Bad, interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), Akt, PI3K, and NF-κB were determined.Results: Comprehensive gene expression profiling analysis identified that CXCL8 might affect the development of ischemic stroke through regulating the PI3K/Akt/ NF-κB-signaling pathway. CXCL8 silencing significantly reduced deflection index and infarct size, improved neurological function, and suppressed neuroglial cell loss and apoptosis index. In addition, glial fibrillary acidic portein (GFAP) and ionized calciumbinding adapter molecule 1 (IBA-1) expressions were decreased following CXCL8 suppression, suggesting CXCL8 affected neuroglial activation. Importantly, we also found that CXCL8 silencing activated neuroglial cell and suppressed inflammatory cytokine production in ischemic stroke mice.Conclusion: Taken together, these findings highlight that functional suppression of CXCL8 promotes neuroglial activation and inhibits neuroinflammation by regulating the PI3K/Akt/NF-κB-signaling pathway in mice with ischemic stroke, which might provide new insight for ischemic stroke treatment. K E Y W O R D S chemokine (C-X-C motif) ligand 8, ischemic stroke, neuroglial cell, neuroinflammation, PIK/Akt/NF-κB pathway J Cell Physiol. 2019;234:7341-7355.wileyonlinelibrary.com/journal/jcp