An increase in the cerebral infarction area during fatigue is mediated by il-6 through an induction of fibrinogen synthesis

OBJECTIVES: Our study aimed to investigate the impact of fatigue on the severity of stroke and to explore the underlying mechanisms. METHODS: Fatigued male rats underwent middle cerebral artery occlusion and the infarcted brain area was determined. Then, coagulation parameters were assessed in the fatigued group and a control group. In addition, the level of fibrinogen was determined in rats deprived of sleep for various numbers of days. To study whether interleukin-6 was involved in fibrinogen synthesis during fatigue, we also measured levels of interleukin-6 in rats deprived of sleep for various numbers of days. Furthermore, brain injury by middle cerebral artery occlusion was measured in wild-type mice, interleukin-6(-/-) mice and wild-type mice treated with bezafibrate. RESULTS: More severe cerebral infarction was observed in the fatigued rats, resulting in an infarct ratio of 23.4%. The infarct ratio was significantly increased in the fatigued rats compared with that in the control group (8%, p, < 0.05). The level of fibrinogen was increased significantly in the fatigued rats compared with that in the control group. In addition, a marked reduction in fibrinogen level was observed in the fatigued interleukin-6(-/-) mice compared to their wild-type counterparts, whereas no difference was observed between fatigued wildtype mice and interleukin-6(-/-) rats treated with recombinant human interleukin-6. The reduction in brain injury due to middle cerebral artery occlusion during fatigue was observed in interleukin-6(-/-) mice and wild-type mice treated with bezafibrate. CONCLUSION: Fatigue could increase stroke severity and was associated with the interleukin-6-induced expression of fibrinogen.