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Hypoxic-ischemic neonatal encephalopathy due to perinatal asphyxia is the leading cause of brain injury in newborns. Clinical data suggest that brain inflammation induced by perinatal insults can persist for years. We previously showed that signaling through the receptor for complement peptide C3a (C3aR) protects against cognitive impairment induced by experimental perinatal asphyxia. To investigate the long-term neuropathological effects of hypoxic-ischemic injury to the developing brain and the role of C3aR signaling therein, we subjected wildtype mice, C3aR deficient mice, and mice expressing biologically active C3a in the CNS to mild hypoxic-ischemic brain injury on postnatal day 9. We found that such injury triggers neurodegeneration and pronounced reactive gliosis in the ipsilesional hippocampus both of which persist long into adulthood. Transgenic expression of C3a in reactive astrocytes reduced hippocampal neurodegeneration and reactive gliosis. In contrast, neurodegeneration and microglial cell density increased in mice lacking C3aR. Intranasal administration of C3a for 3 days starting 1 h after induction of hypoxia-ischemia reduced neurodegeneration and reactive gliosis in the hippocampus of wildtype mice. We conclude that neonatal hypoxic-ischemic brain injury leads to long-lasting neurodegeneration. This neurodegeneration is substantially reduced by treatment with C3aR agonists, conceivably through modulation of reactive gliosis.

In this study, copper oxide nanoparticles (CuO NPs) were green synthesized using the leaf extract of Momordica cochinchinensis (Lour.). Various characterization techniques such as Energy-dispersive x-ray spectroscopy (EDS), Ultraviolet Visible (UV–vis) Spectroscopy, x-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and Fourier-transform Infrared (FTIR) Spectroscopy were utilized to study the formation of CuO NPs. DLS and TEM analysis revealed the formation of sphere-shaped CuO NPs with mean particle size of 56 nm. Additionally, the prepared CuO NPs were incubated with Hepatic (HepG2) cells to check their cel viability and evaluate the formation of reactive oxygen species (ROS). The results of the current work exhibited a concentration-dependent decline in the viability of HepG2 cells with half maximal inhibitory concentration (IC50) value of 75 μg ml−1. The cytotoxic effect of CuO NPs was responsible for the cell apoptosis as well as ROS induction in the HepG2 cells. Further, the prepared CuO NPs could act as possible chemotherapeutic agent for the treatment of liver hepatocellular carcinoma (HCC) in future.

hold United States and European patent "C3a receptor agonists for use against ischemic brain injury, stroke, traumatic brain injury, spinal cord injury and neurodegenerative disorders" (US 11,266,715, EP 3541402). M. Pekna has served as consultant for Merck KGaA outside the submitted work. The other authors have declared that no conflict of interest exists.

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