Paracrine Interleukin 6 induces cerebral remodeling at early stages after unilateral common carotid artery occlusion in mice

ABSTRACT: Carotid artery disease is frequent and can result in chronic modest hypoperfusion of the brain causing cognitive impairments even if classified asymptomatic without a transient ischemic attack or stroke. Paracrine Interleukin 6 (IL 6) improves functional outcome after stroke. However, in carotid artery disease it might have adverse long-term effects. With this exploratory study, we investigated the effect of paracrine IL 6 on cerebral remodeling in early stages after asymptomatic carotid artery occlusion. Therewith we aimed to distinguish IL 6 dependent targets with beneficial effects for long-term outcome from factors causing the detrimental long-term effects of IL 6. To mimic a human asymptomatic carotid artery disease, we used a mouse model of unilateral common carotid artery (CCA) occlusion. We developed a mouse model for inducible paracrine cerebral IL 6 expression (Cx30-Cre-ERT2;FLEX IL6) and induced IL 6 two days after CCA occlusion. We studied the effects of paracrine IL 6 after CCA occlusion on neuronal connectivity using diffusion tensor imaging and on local proteome regulations of the hypo-perfused striatum and contralateral motor cortex using mass spectrometry of laser capture micro-dissected tissues. Paracrine IL-6 induced cerebral remodeling leading to increased inter-hemispheric connectivity and changes in motor system connectivity. We identified changes in local protein abundance which might have adverse effects on functional outcome such as upregulation of Synuclein gamma (Sncg) or downregulation of Proline Dehydrogenase 1 (Prodh). However, we also identified changes in local protein abundance having potentially beneficial effects such as upregulation of Caprin1 or downregulation of GABA transporter 1 (Gat1).

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Carotid Artery Occlusion

SUBMITTER: Marieluise Kirchner  

LAB HEAD: Philipp Mertins

PROVIDER: PXD029737 | Pride | 2022-01-27

REPOSITORIES: Pride