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-1β 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.
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http://dx.doi.org/10.1038/s41401-024-01323-7 | DOI Listing |
Neuroscience
December 2024
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address:
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disorder of the central nervous system (CNS) targeting myelinated axons. Pathogenesis of MS entails an intricate genetic, environmental, and immunological interaction. Dysregulation of immune response i.
View Article and Find Full Text PDFComp Biochem Physiol Part D Genomics Proteomics
December 2024
College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, China. Electronic address:
Hypoxia disrupts multiple physiological processes, including metabolism, immunity, and reproduction in teleosts. The brain plays a critical role in adapting to environmental changes, regulating the endocrine system, and controlling reproduction. The present study investigated the sex-specific cerebral responses to chronic hypoxia through an integrated analysis of the transcriptome, proteome, and metabolome of yellow catfish.
View Article and Find Full Text PDFJ Neuroimmunol
December 2024
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:
Background And Objectives: Guhong injection (GHI) has multiple components and generates diverse effects, and is mainly used in the treatment of acute ischemic stroke (AIS). The purpose of this study is to explore the multiple effects of GHI in AIS models in mice and the mechanism how they work together to affect the stroke outcome.
Methods: Middle cerebral artery occlusion (MCAO) and photothrombotic stroke models were established with GHI or vehicle.
Mol Neurobiol
December 2024
Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamedan, Iran.
There is no acquiesced remedy for the treatment of traumatic brain injury (TBI)-associated impairment, especially cognitive decline. The first 24 h after TBI is a golden time for preventing the progress of the impairments. The present study aimed to examine the acute effects of fucoidan on neurological outcomes and memory performance and investigate its potential mechanisms in rats with TBI.
View Article and Find Full Text PDFChem Biodivers
December 2024
UFPA: Universidade Federal do Para, Biological Science, Rua Augusto Corrêa S/N, Guamá, Belém 66075-900, Pará, Brazil, Belem, BRAZIL.
Oxidative stress is a pivotal factor in the pathogenesis of malaria, contributing to the development of conditions such as anemia, respiratory complications, and cerebral malaria. To counteract oxidative damage, we evaluated the effects of vitamin E (α-TOH) and D-α-tocopherol polyethylene glycol succinate 1000 (TPGS) supplementation on parasitemia progression, mortality rate, and blood-brain barrier (BBB) permeability in Plasmodium berghei ANKA-infected mice. The mice were divided into four groups: a control group (untreated and uninfected), an infected group (Pb), a TPGS+Pb group, and an α-TOH+Pb group.
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