Abstract
As one form of stroke, intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease, which has high morbidity and mortality and lacks effective medical treatment. Increased infiltration of inflammatory cytokines coupled with pyroptotic cell death is involved in the pathophysiological process of ICH. However, little is known about whether concomitant fracture patients have the same progression of inflammation and pyroptosis. Hence, we respectively established the mouse ICH model and ICH with bilateral tibial fracture model (MI) to explore the potential cross-talk between the above two injuries. We found that MI obviously reversed the expressions of pyroptosis-associated proteins, which were remarkably up-regulated at the acute phase after ICH. Similar results were observed in neuronal expressions via double immunostaining. Furthermore, brain edema was also significantly alleviated in mice who suffered MI, when compared with ICH alone. To better clarify the potential mechanisms that mediated this cross-talk, recombinant mouse interleukin-13 (IL-13) was used to investigate its effect on pyroptosis in the mouse MI model, in which a lower level of IL-13 was observed. Remarkably, IL-13 administration re-awakened cell death, which was mirrored by the re-upregulation of pyroptosis-associated proteins and PI-positive cell counts. The results of hemorrhage volume and behavioral tests further confirmed its critical role in regulating neurological functions. Besides, the IL-13-treated MI group showed poor outcomes of fracture healing. To sum up, our research indicates that controlling the IL-13 content in the acute phase would be a promising target in influencing the outcomes of brain injury and fracture, and meanwhile, provides new evidence in repairing compound injuries in clinics.
Highlights
Intracerebral hemorrhage (ICH) is defined as spontaneous, nontraumatic bleeding into the parenchyma of the brain [1]
In order to explore the effect of tibial fracture on pyroptosis induced by intracerebral hemorrhage (ICH), mice in different models were sacrificed at 24 h post-injury
While, compared with ICH group, decreased expression levels of these proteins were observed in the MI group, and no changes were examined in the Tibial fracture (TF) group relative to sham group (Sham) group (Fig. 2a, b)
Summary
Intracerebral hemorrhage (ICH) is defined as spontaneous, nontraumatic bleeding into the parenchyma of the brain [1]. It is a serious disease which lead to severe disability and even death that substantially impacting public health. Previous researches have shown a mortality rate of up to 40% within a month of ICH [2, 3], which accounted for 10–15% of strokes worldwide each year [4]. Thereafter, the secondary injuries induced by the toxic products of blood, excitotoxicity, oxidative stress, and inflammation occur. These insults trigger irreversibly damage to the neurovascular unit, and to death [5]
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