title: Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor.
abstract: Platelet-activating factor (PAF) is a unique phosphoglycerine that mediates the biological functions of both immune and nervous systems. Excessive PAF plays an important role in neural injury via its specific receptor (PAFR). In this study, we hypothesized that PAF signaling activates reactive gliosis after spinal cord injury (SCI), and blocking the PAF pathway would modify the glia scar formation and promote functional recovery. PAF microinjected into the normal wild-type spinal cord induced a dose-dependent activation of microglia and astrocytes. In the SCI mice, PAFR null mutant mice showed a better functional recovery in grip and rotarod performances than wild-type mice. Although both microglia and astrocytes were activated after SCI in wild-type and PAFR null mutant mice, expressions of IL-6, vimentin, nestin, and GFAP were not significantly elevated in PAFR null mutants. Disruption of PAF signaling inhibited the expressions of proteoglycan CS56 and neurocan (CSPG3). Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at 7 dpi but more NFH-labeled axons at 28 dpi was found in the area adjacent to the epicenter in PAFR null mutant SCI mice. Moreover, treatment with PAFR antagonist Ginkgolide B (GB) at the chronic phase rather than acute phase enhanced the functional recovery in the wild-type SCI mice. These findings suggest that PAF signaling participates in reactive gliosis after SCI, and blocking of this signaling enhances functional recovery and to some extent may promote axon regrowth.
authors.affiliation: Department of Spine Surgery, First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin, 130021, People's Republic of China.|Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Donald Baxter Building, Suite 321B, Louisville, KY, 40202, USA.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Donald Baxter Building, Suite 321B, Louisville, KY, 40202, USA.|Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Zhongwen
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Norton Healthcare, Norton Neuroscience Institute, Louisville, KY, 40202, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Donald Baxter Building, Suite 321B, Louisville, KY, 40202, USA.|Department of Orthopedics, General Hospital of Tianjin Medical University, Tianjin, 300052, China.
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Feng
authors.affiliation: Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Donald Baxter Building, Suite 321B, Louisville, KY, 40202, USA.|Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Norton Healthcare, Norton Neuroscience Institute, Louisville, KY, 40202, USA.
authors.forename: Lisa B E
authors.initials: LBE
authors.lastname: Shields
authors.affiliation: Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Donald Baxter Building, Suite 321B, Louisville, KY, 40202, USA.|Pharmacy School, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, 130033, China. drzqs@yahoo.com.cn.
authors.forename: Qingsan
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Comer Children's Hospital, Department of Pediatrics, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
authors.affiliation: Norton Healthcare, Norton Neuroscience Institute, Louisville, KY, 40202, USA.|Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Shields
authors.affiliation: Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Donald Baxter Building, Suite 321B, Louisville, KY, 40202, USA. j0cai002@louisville.edu.|Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, 40202, USA. j0cai002@louisville.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism; D002574:Cervical Vertebrae / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005552:Forelimb / Q000503:physiopathology; D005911:Gliosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor
keywords: Astrocyte; Axon regeneration; Dorsal laceration; Glial scar; Spinal cord injury