RESUMEN
The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.
RESUMEN
BACKGROUND: Pollen is a common plant-derived food source for predatory ladybird beetles under field conditions, yet the potential for pollen to improve the quality of artificial diets remains largely unexplored. In this study, we developed three pollen diets by incorporating varying proportions of canola bee pollen (7.5%, 15.0% and 22.5% with 2.5%, 5.0%, and 7.5% of water, respectively) into a conventional diet. The feeding efficiency of Harmonia axyridis, an omnivorous predator, was evaluated and compared on three pollen diets, a conventional nonpollen diet and pea aphids. RESULTS: The larvae fed a medium or high pollen diet exhibited significantly higher survival in the 4th instar, pupa and adult stages than those fed a nonpollen diet. These larvae also developed into significantly heavier adults, and their survival rates in adulthood were comparable to those fed pea aphids. Specifically, we revealed the underlying mechanisms through which a high pollen diet enhances pupal development. Consumption of high pollen diet versus nonpollen diet resulted not only in a significant decrease in pupal glycogen content, but also an increase in adult lipid content. Both diet treatments induced similar changes in carbohydrate and glycogen content compared to the aphid diet while exhibiting different alterations in pupal protein content and adult lipid content. Furthermore, the transcriptome analysis revealed that the nutrient metabolism, immune response, and cuticle development pathways were predominantly enriched among the differentially expressed genes (DEGs). CONCLUSION: Canola bee pollen offers diverse advantages in terms of rearing H. axyridis larvae with an artificial diet, which will advance the development of effective diets for predaceous coccinellids. © 2024 Society of Chemical Industry.