Blood-brain barrier dysfunction in cerebral arteriovenous malformations. A murine model of hypoperfusion-reperfusion
Leire Pedrosa1,2, Alejandra Mosteiro2,3, Marta Codes3
1Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Introduction:
The presence of an arteriovenous malformation in the brain (bAVM) induces hemodynamic changes, namely chronic hypoperfusion, loss of autoregulation and venous congestion, leading to blood-brain barrier (BBB) dysfunction. Conversely, bAVM treatment is thought to modify this longstanding hemodynamic condition abruptly, potentially leading to adverse responses in the surrounding brain. We designed and validated a murine model that mimics the hypoperfusion-reperfusion effect of bAVM and assessed BBB changes with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Objective:
The goal is to explore perfusion alterations during bAVM progression and after surgical intervention, using DCE-MRI to track changes in real time.
Methods:
Cerebral hypoperfusion and venous congestion were induced in rats by bilateral external carotid artery ligation and unilateral jugular-carotid anastomosis. 21 days were allowed for chronic adaptative changes, then the fistula was closed by jugular ligation for reperfusion. Neurological examination and MRI were performed at 1, 7, and 21 days of evolution and 24 h after ligation. DCE findings was confirmed by IgG immunofluorescence.
Results:
MRI observations confirmed that the model successfully replicates arterial hypoperfusion and venous hypertension without signs of malignant oedema or ischemia. Neurofunctional assessment showed a progressive neurological decline with a tendency to improvement after shunt ligation. DCE-MRI showed progressive BBB disruption and restoration after ligation, objectively quantified by increases in Ktrans values. Similar results were obtained by immunofluorescence analysis.
Conclusion:
Our model provides a dynamic platform to investigate cerebral perfusion changes associated with bAVM progression and surgical resolution, offering novel insights into disease mechanisms and potential therapeutic strategies.
