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Hippocampal Deformations and Entorhinal Cortex Atrophy as an Anatomical Signature of Long-Term Cognitive Impairment: from the MCAO Rat Model to the Stroke Patient

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Abstract

Stroke patients have an elevated risk of developing long-term cognitive disorders or dementia. The latter is often associated with atrophy of the medial temporal lobe. However, it is not clear whether hippocampal and entorhinal cortex atrophy is the sole predictor of long-term post-stroke dementia. We hypothesized that hippocampal deformation (rather than atrophy) is a predictive marker of long-term post-stroke dementia on a rat model and tested this hypothesis in a prospective cohort of stroke patients.

Male Wistar rats were subjected to transient middle cerebral artery occlusion and assessed 6 months later. Ninety initially dementia-free patients having suffered a first-ever ischemic stroke were prospectively included in a clinical study. In the rat model, significant impairments in hippocampus-dependent memories were observed. MRI studies did not reveal significant atrophy of the hippocampus volume, but significant deformations were indeed observed—particularly on the ipsilateral side. There, the neuronal surface area was significantly lower in ischemic rats and was associated with a lower tissue density and a markedly thinner entorhinal cortex. At 6 months post-stroke, 49 of the 90 patients displayed cognitive impairment (males 55.10%). Shape analysis revealed marked deformations of their left hippocampus, a significantly lower entorhinal cortex surface area, and a wider rhinal sulcus but no hippocampal atrophy. Hence, hippocampal deformations and entorhinal cortex atrophy were associated with long-term impaired cognitive abilities in a stroke rat model and in stroke patients. When combined with existing biomarkers, these markers might constitute sensitive new tools for the early prediction of post-stroke dementia.

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Acknowledgements

This work was funded by the Nord-Pas-de-Calais Regional Council, Lille University Hospital, the French Ministry of Health, and the Fondation Coeur et Artères. We thank A. Ponchel and V. Chenal for the neuropsychological evaluation of the stroke patients. We also thank N. Durieux (from the University of Lille’s in vivo imaging core facility), C. Laloux (from the SFR DN2M functional testing core facility), M. Tardivel (from the Lille Bioimaging Centre), and the Lille Animal Facilities for technical advice and access to equipment. CC is a member of the Institut Universitaire de France.

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Author notes

  1. C. Delattre and C. Bournonville contributed equally to this work

Authors and Affiliations

  1. U1171 - Degenerative & Vascular Cognitive Disorders, Université Lille, INSERM, CHU Lille, Université du Littoral Côte d’Opale, 59000, Lille, France

    C. Delattre, C. Bournonville, F. Auger, R. Lopes, C. Delmaire, H. Henon, A. M. Mendyk, S. Bombois, J. C. Devedjian, D. Leys, C. Cordonnier & M. Bastide

  2. U1171 - Degenerative & Vascular Cognitive Disorders, Faculté de Médecine, Université Lille, INSERM, CHU Lille, 1 place de Verdun, 59045, Lille cedex, France

    M. Bastide

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  1. C. Delattre
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Correspondence to M. Bastide.

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All patients provided their written, informed consent to participation in the study. The study’s protocol and objectives were approved by the local independent ethics committee (CPP Nord Ouest IV, Lille, France; reference: 2009-A00141-56, March 17th, 2009).

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The authors declare that they have no conflict of interest.

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Delattre, C., Bournonville, C., Auger, F. et al. Hippocampal Deformations and Entorhinal Cortex Atrophy as an Anatomical Signature of Long-Term Cognitive Impairment: from the MCAO Rat Model to the Stroke Patient. Transl. Stroke Res. 9, 294–305 (2018). https://doi.org/10.1007/s12975-017-0576-9

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  • DOI: https://doi.org/10.1007/s12975-017-0576-9

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