Features Of DCE-MRI And Relationship Of TWEAK Pathway In Systemic Lupus Erythematosus With Cognitive Dysfunction

Objectives:Systemic lupus erythematosus(SLE)complicated with cognitive dysfunction(CD)is common,and previous imaging studies have found cognitive dysfunction,as well as craniocerebral microlesions or brain area dysfunction.This study hypothesized that the cognitive impairment of patients with SLE may be related to changes in blood-brain barrier permeability.It is planned to perform dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)scans of SLE patients to explore The relationship between blood brain barrier permeability changes reflected by DCE-MRI imaging features and cognitive impairment;studies have found that Tumor necrosis factor like weak inducer of apoptosis(TWEAK)may affect BBB This study also prepared and used the SLE model MRL/lpr mice to initially explore the effect of TWEAK on synaptic plasticity of hippocampal pyramidal neurons,in order to further study the molecules of cognitive dysfunction in neuropsychiatric lupus(NPSLE)And lay the foundation for electrophysiological mechanisms.Methods:The DCE-MRI examination was performed on SLE patients and healthy volunteers who were admitted to the Rheumatology and Immunology Department of the First Affiliated Hospital of Kunming Medical University from May 2016 to October 2018,and calculate the Ktrans value by comparing healthy volunteers,SLE and SLE combined Differences in brain Ktrans values of patients with cognitive impairment,looking for the Mini-mental status examination(MMSE),Forward Digit Span(FDS)and Backward Digit Span(BDS)scales Associated brain regions.The patch-clamp system was used to detect long-term potentiation(LTP)and short-term potentiation(STP)of hippocampal CA1 synaptic plasticity,and further explore TWEAK’s effect on model mouse hippocampus.The influence of CA1 synaptic plasticity will lay the foundation for the future search for the molecular and electrophysiological mechanisms of NPSLE cognitive dysfunction.Results:In total,60 SLE patients and 23 healthy volunteers were included.There was no statistical difference in age and gender between the two groups.The Ktrans values of the whole brain and bilateral hippocampus of SLE patients were not significantly different from those of controls,Correlation analysis found that the MMSE’s orientation,attention,computing power score and BDS were closely related to the frontal brain area(central anterior gyrus,upper frontal gyrus,middle frontal gyrus,and lower frontal gyrus),while recall,memory score,FDS and BDS were It is closely related to the temporal lobe(eg superior temporal gyrus,middle temporal gyrus,inferior temporal gyrus,fusiform gyrus,temporal pole)and marginal lobe(parahippocampal gyrus,hippocampus).Studies on isolated brain slices of animals found that TWEAK had no effect on synaptic transmission STP of hippocampal CA1 vertebral neurons in isolated brain slices of mice(P=0.178),but could significantly inhibit C57BL/6 mice and MRL/lpr LTP of CA1 vertebral neurons in isolated rat brain slices(P<0.001).Conclusion:the conclusion of this study as follows:(1)The Ktrans values of the whole brain and bilateral hippocampus of SLE patients are not different from those of the control,suggesting that there is no obvious abnormality in the permeability of the blood brain barrier in the patient and the hippocampus in general.(2)In the patient group,the middle frontal lobe(such as the central anterior gyrus,upper frontal gyrus,middle frontal gyrus,and inferior frontal gyrus),the temporal lobe(such as the upper temporal gyrus,middle temporal gyrus,lower temporal gyrus,fusiform gyrus,and temporal pole)and The marginal lobe(hippocampal gyrus,hippocampus)Ktrans value is negatively correlated with the score of cognitive function,suggesting that the permeability of the blood-brain barrier in these brain regions may affect the cognitive function of patients.(3)TWEAK,which is related to the blood-brain barrier function,can cause the long-term synaptic enhancement of hippocampal pyramidal neurons to be significantly weakened or disappeared,which may be one of the molecular mechanisms of TWEAK/Fn14 leading to cognitive dysfunction.