title: Intraventricular apolipoprotein ApoJ infusion acts protectively in Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in youth, but to date, effective therapies are still lacking. Previous studies revealed a marked response of apolipoprotein J (ApoJ) expression to the brain injury. The aim of this study was to determine the potential roles of ApoJ in functional recovery following TBI. After controlled cortex impact (CCI), a TBI model, in adult wild-type mice, ApoJ expression was up-regulated since 6 h post-injury and sustained for 5 days. Animals infused with recombinant human ApoJ intraventricularly at 30 min prior to CCI showed significantly reduced oxidative stress (3-nitrotyrosine, 4-hydroxynonenal) and complement activation (C5b-9). In addition, ApoJ treatment was shown to suppress the inflammatory response (glial activation, cytokine expression), blood-brain barrier disruption (Evans blue extravasation), and cerebral edema (water content) induced by CCI. Concomitantly, improved neuronal maintenance and neurological behavioral performance were observed in ApoJ-treated mice compared with the vehicle group. These findings support a neuroprotective role of ApoJ via multifunctional pathways, providing a novel and encouraging treatment strategy for TBI. Apolipoprotein J (ApoJ) was up-regulated after controlled cortical impact (CCI). Mice infused with human recombinant ApoJ prior to CCI showed reduced expression of complement and oxidative marker proteins as well as reduced inflammatory response and attenuated blood-brain barrier (BBB) disruption and cerebral edema. Neuronal maintenance and behavioral performance were improved by ApoJ infusion. These findings demonstrated the protective function of ApoJ for traumatic brain injury (TBI) therapy.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Chongjie
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Neurology and Radiology, Neuroprotection Research Laboratory, Harvard Medical School, Cambridge, MA, USA.
authors.forename: Zhanyang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Cerebrovascular, the Affiliated Hospital of Zunyi Medical College, Guizhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zongduo
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051152:Clusterin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D057967:Infusions, Intraventricular; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000447:Aldehydes; D051152:Clusterin; D018696:Neuroprotective Agents; C002744:3-nitrotyrosine; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal
keywords: ApoJ; TBI; complement cascade; oxidative stress