title: Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control.
abstract: Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4(-/-) mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: C
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military University, Xi'an, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: He
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Liang
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.affiliation: Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.affiliation: School of Psychology, Nanjing Normal University, Nanjing, China.
authors.forename: T F
authors.initials: TF
authors.lastname: Yuan
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Pei
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: H
authors.initials: H
authors.lastname: Su
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency / Q000235:genetics; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D012189:Retrospective Studies; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D014057:Tomography, X-Ray Computed; D014657:Vasculitis / Q000209:etiology*; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4