Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones.

AIMS: The antiphospholipid syndrome (APS) is an autoimmune disease characterized by high titres of auto-antibodies (aPL) leading to thrombosis and consequent infarcts. However, many affected patients develop neurological symptoms in the absence of stroke. Similarly, in a mouse model of this disease (eAPS), animals consistently develop behavioural abnormalities despite lack of ischemic brain injury. Therefore, the present study was designed to identify structural alterations of hippocampal neurones underlying the neurological symptoms in eAPS. METHODS: Adult female Balb/C mice were subjected to either induction of eAPS by immunization with ß2-Glycoprotein 1 or to a control group. After sixteen weeks animals underwent behavioural and cognitive testing using Staircase test (experiment 1 and 2) and Y-maze alternation test (experiment 1) and were tested for serum aPL levels (both experiments). Animals of experiment 1 (n = 7/group) were used for hippocampal neurone analysis using Golgi-Cox staining. Animals of experiment 2 (n = 7/group) were used to analyse molecular markers of total dendritic integrity (MAP2), presynaptic plasticity (synaptobrevin 2/VAMP2) and dendritic spines (synaptopodin) using immunohistochemistry. RESULTS: eAPS mice developed increased aPL titres and presented with abnormal behaviour and impaired short term memory. Further, they revealed a reduction of dendritic complexity of hippocampal CA1 neurones as reflected by decreased dendritic length, arborization and spine density, respectively. Additional decrease of the spine-associated protein expression of Synaptopodin points to dendritic spines as major targets in the pathological process. CONCLUSION: Reduction of hippocampal dendritic complexity may represent the structural basis for the behavioural and cognitive abnormalities of eAPS mice.

Layer-specific analysis of myocardial function for accurate prediction of reversible ischaemic dysfunction in intermediate viability defined by contrast-enhanced MRI.

BACKGROUND: Contrast-enhanced MRI (ceMRI) has impaired accuracy in the prediction of functional recovery after revascularisation in cases of intermediate myocardial viability. OBJECTIVE: To evaluate the predictive value of layer-specific myocardial deformation analysis for improvement in ischaemic dysfunction after revascularisation. METHODS: In 132 patients with ischaemic left ventricular dysfunction undergoing revascularisation, myocardial viability was assessed by pixel-tracking-derived myocardial deformation imaging and ceMRI. Peak systolic circumferential strain was determined for total wall thickness and for three myocardial layers (endocardial, mid-myocardial and epicardial) in a 16-segment model. Analysis to predict recovery of function at 8±2 months after revascularisation was performed considering all dysfunctional segments or only segments with intermediate viability by ceMRI (hyperenhancement 25-75%, N=735 segments). RESULTS: Segments with functional recovery (N=568) had higher circumferential strain in all myocardial layers and a smaller degree of hyperenhancement than segments without functional recovery (N=433). Analysis of all dysfunctional segments showed that the predictive accuracy for functional recovery was high for endocardial strain, total wall thickness strain and hyperenhancement by ceMRI (area under the curve (AUC) 0.883, 0.782 and 0.834, respectively). Considering only segments with intermediate viability by ceMRI, endocardial circumferential strain allowed prediction of functional recovery with higher accuracy (specificity 75%, sensitivity 78%, AUC=0.811, 95% CI 0.776 to 0.851) than hyperenhancement analysis (specificity 59%, sensitivity 72%, AUC=0.705, 95% CI 0.659 to 0.747, p<0.05). CONCLUSION: Analysis of layer-specific myocardial function using deformation imaging allows accurate identification of reversible myocardial dysfunction. In segments with intermediate viability analysis of layer-specific deformation may have special advantages for prediction of functional recovery.