title: Interleukin-6 mediates enhanced thrombus development in cerebral arterioles following a brief period of focal brain ischemia.
abstract: OBJECTIVE
  The cerebral microvasculature is rendered more vulnerable to thrombus formation following a brief (5.0 min) period of focal ischemia. This study examined the contribution of interleukin-6 (IL-6), a neuroprotective and prothrombotic cytokine produced by the brain, to transient ischemia-induced thrombosis in cerebral arterioles.
  
  
  RESULTS
  The middle cerebral artery of C57BL/6J mice was occluded for 5 min, followed by 24h of reperfusion (MCAo/R). Intravital fluorescence microscopy was used to monitor thrombus development in cerebral arterioles induced by light/dye photoactivation. Thrombosis was quantified as the time of onset of platelet aggregation on the vessel wall and the time for complete blood flow cessation. MCAo/R in wild type (WT) mice yielded an acceleration of thrombus formation that was accompanied by increased IL-6 levels in plasma and in post-ischemic brain tissue. The exaggerated thrombosis response to MCAo/R was blunted in WT mice receiving an IL-6 receptor-blocking antibody and in IL-6 deficient (IL-6(-/-)) mice. Bone marrow chimeras, produced by transplanting IL-6(-/-) marrow into WT recipients, did not exhibit protection against MCAo/R-induced thrombosis.
  
  
  CONCLUSIONS
  The increased vulnerability of the cerebral vasculature to thrombus development after MCAo/R is mediated by IL-6, which is likely derived from brain cells rather than circulating blood cells. These findings suggest that anti-IL-6 therapy may reduce the likelihood of cerebral thrombus development after a transient ischemic attack.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Ya Hui
authors.initials: YH
authors.lastname: Tang
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Shantel
authors.initials: S
authors.lastname: Vital
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Russell
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Seifert
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA. Electronic address: dgrang@lsuhsc.edu.
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007839:Functional Laterality; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018715:Microscopy, Video; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D012039:Regional Blood Flow; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism* / Q000601:surgery
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6
keywords: Cerebral arterioles; Interleukin-6; Ischemia-reperfusion; Thrombosis; Transient ischemic attack