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.
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http://dx.doi.org/10.3389/fimmu.2021.768198 | DOI Listing |
Exp Neurol
December 2024
Department of Neurosurgery, University of Cincinnati, Cincinnati, OH 45267, USA; Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH 45267, USA. Electronic address:
Cortical spreading depolarizations (CSDs) are the most common electrophysiological dysfunction following a traumatic brain injury (TBI), and clustered CSDs (≥3 CSDs in 2 h) are associated with poor outcomes 6 months after TBI. While many experimental studies have investigated a single CSD after injury, no known studies have investigated how time after injury affects the characteristics and impact of a CSD cluster. This study sought to determine the characteristics of a cluster of repetitive CSDs when induced at three different time points after moderate experimental TBI.
View Article and Find Full Text PDFExp Eye Res
December 2024
Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200031. Electronic address:
We aimed to explore the protective effects and underlying mechanisms of taurine on retinal cells during acute ocular hypertension (AOH)-induced damage. Retinal morphology, apoptosis, mitochondrial structure, electroretinography, expression of GTP binding protein 3 (GTPBP3), and molecules in the unfolded protein response (UPR) were examined in an AOH mouse model and wild-type (WT) mice with or without intravitreal injection of taurine. For in vitro experiments, the GTPBP3 expression and endoplasmic reticulum (ER) stress were examined in R28 cell line under hydrogen peroxide (HO)-induced damage or hypoxia/reoxygenation (H/R)-induced damage, with or without taurine pretreatment.
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Institute of Physiology and Pathophysiology, Department of Cardiovascular Physiology, Heidelberg University, Heidelberg, Germany.
Severity and outcome of strokes following cerebral hypoperfusion are significantly influenced by stress responses of the blood vessels. In this context, brain endothelial cells (BEC) regulate inflammation, angiogenesis and the vascular resistance to rapidly restore perfusion. Despite the relevance of these responses for infarct volume and tissue recovery, their transcriptional control in BEC is not well characterized.
View Article and Find Full Text PDFCrit Care
December 2024
Département d'anesthésie Réanimationéanimation, DMU PARABOL, AP-HP, Hôpital Beaujon, Clichy, France.
Hum Exp Toxicol
December 2024
Department of neurology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China. Hubei Sizhen Laboratory, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China.
Introduction: The incidence of cerebral ischemia-reperfusion injury (I/R) is complex which seriously threatens the life safety of patients. Neither its prevention nor its treatment has been successful so far. Proteins that bind to DNA and belong to the C2/H2 zinc finger family are known as Krüppel-like factors (KLFs).
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