High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective To explore the clinical efficacy of embodied motor imagery training(MIT)combined with acupuncture in improving upper limb motor function after ischemic stroke,and to understand the potential brain mechanism of the combined therapy through resting state functional MRI(fMRI).Methods A total of 36 patients with first cerebral infarction admitted to our hospital were randomly divided into control group and experimental group.The control group received routine rehabilitation+acupuncture treatment,and the experimental group received routine rehabilitation+embodied MIT combined with acupuncture treatment.Each training lasted for 60 min,once a day,5 days a week,for a total of 8 weeks.Before and after treatment,Fugl-Meyer assessment(FMA)and modified Barthel index(MBI)were used to evaluate the upper limb motor function and daily living ability of the patients,and fMRI data of the whole brain in resting state were collected to calculate the amplitude of low frequency fluctuation(fALFF)and z-score(zfALFF).Repeated measures analysis of variance was used to analyze the interaction effect of group x time,the main effect of group and the main effect of time.Results After treatment,the FMA score of the experimental group increased from(16.83±3.00)to(27.89±3.99),and the MBI score increased from(26.11±6.31)to(59.22±9.47).Compared with the control group,the differences were statistically significant(all P＜0.05).The fMRI data showed that the zfALFF of the lesion-side supplementary motor area,inferior parietal angular gyrus,triangular inferior frontal gyrus,supramarginal gyrus and middle temporal gyrus were significantly increased in the experimental group,while the zfALFF of the lesion-side supplementary motor area,postcentral gyrus,triangular inferior frontal gyrus,supramarginal gyrus and middle temporal gyrus were significantly decreased in the control group.The increased amplitude of zfALFF in the lesion-side supplementary motor area and supramarginal gyrus was significantly positively correlated with the increased amplitude of FMA(all P＜0.0 5).Conclusions Embodied MIT combined with acupuncture and routine rehabilitation can significantly improve the upper limb motor function and daily living ability of patients with cerebral infarction.The functional improvement is related to the neural activity and pathway activation in the lesion side auxiliary motor area,inferior parietal angular gyrus,triangular inferior frontal gyrus,supramarginal gyrus,middle temporal gyrus and bilateral postcentral gyrus.

Objective To explore the clinical efficacy of embodied motor imagery training(MIT)combined with acupuncture in improving upper limb motor function after ischemic stroke,and to understand the potential brain mechanism of the combined therapy through resting state functional MRI(fMRI).Methods A total of 36 patients with first cerebral infarction admitted to our hospital were randomly divided into control group and experimental group.The control group received routine rehabilitation+acupuncture treatment,and the experimental group received routine rehabilitation+embodied MIT combined with acupuncture treatment.Each training lasted for 60 min,once a day,5 days a week,for a total of 8 weeks.Before and after treatment,Fugl-Meyer assessment(FMA)and modified Barthel index(MBI)were used to evaluate the upper limb motor function and daily living ability of the patients,and fMRI data of the whole brain in resting state were collected to calculate the amplitude of low frequency fluctuation(fALFF)and z-score(zfALFF).Repeated measures analysis of variance was used to analyze the interaction effect of group x time,the main effect of group and the main effect of time.Results After treatment,the FMA score of the experimental group increased from(16.83±3.00)to(27.89±3.99),and the MBI score increased from(26.11±6.31)to(59.22±9.47).Compared with the control group,the differences were statistically significant(all P＜0.05).The fMRI data showed that the zfALFF of the lesion-side supplementary motor area,inferior parietal angular gyrus,triangular inferior frontal gyrus,supramarginal gyrus and middle temporal gyrus were significantly increased in the experimental group,while the zfALFF of the lesion-side supplementary motor area,postcentral gyrus,triangular inferior frontal gyrus,supramarginal gyrus and middle temporal gyrus were significantly decreased in the control group.The increased amplitude of zfALFF in the lesion-side supplementary motor area and supramarginal gyrus was significantly positively correlated with the increased amplitude of FMA(all P＜0.0 5).Conclusions Embodied MIT combined with acupuncture and routine rehabilitation can significantly improve the upper limb motor function and daily living ability of patients with cerebral infarction.The functional improvement is related to the neural activity and pathway activation in the lesion side auxiliary motor area,inferior parietal angular gyrus,triangular inferior frontal gyrus,supramarginal gyrus,middle temporal gyrus and bilateral postcentral gyrus.