The Study On Interleukin-11 Regulated The Differentiation Of Neural Stem Cells Into Astrocytes And Promoted The Repair Of Brain Damage After Intracerebral Hemorrhage

Background and Purpose:Intracerebral hemorrhage is the hemorrhage caused by non-traumatic rupture of brain parenchyma blood vessel and has a high mortality and poor prognosis.The course of ICH is accompanied by the activation of microglia,astrocytes,and peripheral blood-derived lymphocytes in the brain,causing ipsilateral long-term inflammation.Recent studies have shown that inflammatory response has a close relationship with tissue repair.In particular,activation of gp130 receptor downstream transcription factors(such as stat3,YAP,notch,etc.)has extremely important significance for tissue repair.IL-11 is a member of the gp130 cytokines family.According to reports in the literature and the results of our previous experiments,Interleukin-11(IL-11)had a high expression in ICH patients and mouse models.And our previous experiments showed that IL-11 can promote the differentiation of NSCs into astrocytes.Therefore,we hope to explore the molecular mechanism of IL-11 promoting the differentiation of NSCs into astrocytes and the significance of this phenomenon in the repair of ICH injury in mice.Methods:1.A brain stereotaxic instrument was used to inject collagenase VII into the caudate nucleus of the striatum of the mouse,resulting in an intracerebral hemorrhage model.The constructed intracerebral hemorrhage model was evaluated using a 28-point assessment of neurological impairment and immunofluorescence detection of Ig G in mouse brain sections.2.The level of IL-11 expression in ICH intracerebral and in vitro cell lines was detected by ELISA.3.IL-11 neutralizing antibody was injected into the lateral ventricle of ICH mice.And the effect of IL-11 neutralizing antibody on the proliferation and differentiation of NSCs was detected by immunofluorescence.4.The behavioral changes of ICH mice were detected by corridor experiments and rotarod experiments.5.In vitro use of pure IL-11 protein to stimulate NSCs,the effect of IL-11 on its proliferation and viability under oxygen-glucose deprivation conditions was detected by CCK-8;the differentiation of NSCs by IL-11 stimulation was detected by immunofluorescence and western blot.Results: 1.The ipsilateral level of IL-11 in the mouse ICH model began to increase at 5 days after surgery.2.7 days after ICH,ipsilateral astrocytes and microglia were co-localized with IL-11.In vitro,the secretion level of IL-11 in microglials and monocytes can be improved by LPS stimulation.4.On the 4th day after ICH,NSCs accumulated in the focal area.On the 7th day,NSCs were co-localized with IL-11Rα.5.Intracerebral injection of IL-11 neutralizing antibody impeded the proliferation of NSCs in the lesion area.6.After IL-11 neutralizing antibody injection,the recovery of mouse model’s behavior was hindered.7.In vitro experiment indicate that IL-11 can increase the proliferation of NSCs in differentiation culture system,improve the viability of NSCs under oxygen and glucose deprivation conditions,increase the GFAP expression of NSCs,and increase the level of stat3 phosphorylation.Conclusion:Elevated IL-11 in the brain of ICH mice promotes the recovery of cerebral hemorrhage by increasing the proliferation,differentiation,and viability of NSCs.