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Long-Lasting Cerebral Vasospasm, Microthrombosis, Apoptosis and Paravascular Alterations Associated with Neurological Deficits in a Mouse Model of Subarachnoid Hemorrhage

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Abstract

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and morbidity. Long-term cognitive and sensorimotor deficits are serious complications following SAH but still not well explained and described in mouse preclinical models. The aim of our study is to characterize a well-mastered SAH murine model and to establish developing pathological mechanisms leading to cognitive and motor deficits, allowing identification of specific targets involved in these long-term troubles. We hereby demonstrate that the double blood injection model of SAH induced long-lasting large cerebral artery vasospasm (CVS), microthrombosis formation and cerebral brain damage including defect in potential paravascular diffusion. These neurobiological alterations appear to be associated with sensorimotor and cognitive dysfunctions mainly detected 10 days after the bleeding episode. In conclusion, this characterized model of SAH in mice, stressing prolonged neurobiological pathological mechanisms and associated sensitivomotor deficits, will constitute a validated preclinical model to better decipher the link between CVS, long-term cerebral apoptosis and cognitive disorders occurring during SAH and to allow investigating novel therapeutic approaches in transgenic mice.

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Acknowledgments

We thank the PRIMACEN platform (Normandie Rouen University, France) for imaging equipment and Mr. Arnaud Arabo and Mrs. Huguette Lemonnier for animal housing. This work was supported by Seinari Normandy maturation program, Normandie Rouen University, Inserm, and Rouen University Hospital.

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Authors and Affiliations

  1. INSERM, DC2N, Normandie Univ, UNIROUEN, 76000, Rouen, France

    Mohamad El Amki, Martine Dubois, Antoine Lefevre-Scelles, Nicolas Magne, Mélanie Roussel, Thomas Clavier, Pierre-Olivier Guichet, Emmanuel Gérardin, Vincent Compère & Hélène Castel

  2. Institute for Research and Innovation in Biomedicine (IRIB), 76000, Rouen, France

    Mohamad El Amki, Martine Dubois, Antoine Lefevre-Scelles, Nicolas Magne, Mélanie Roussel, Thomas Clavier, Pierre-Olivier Guichet, Emmanuel Gérardin, Vincent Compère & Hélène Castel

  3. Department of Anesthesiology and Critical Care, Rouen University Hospital, Rouen, France

    Antoine Lefevre-Scelles, Thomas Clavier & Vincent Compère

  4. Department of Radiology, Rouen University Hospital, Rouen, France

    Nicolas Magne & Emmanuel Gérardin

  5. Department of Adult Emergency, Rouen University Hospital, Rouen, France

    Mélanie Roussel

  6. Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, DC2N, Inserm U1239, Team Astrocyte and Vascular Niche, Normandie Univ, UNIROUEN, Place Emile Blondel, 76821, Mont-Saint-Aignan, France

    Hélène Castel

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El Amki, M., Dubois, M., Lefevre-Scelles, A. et al. Long-Lasting Cerebral Vasospasm, Microthrombosis, Apoptosis and Paravascular Alterations Associated with Neurological Deficits in a Mouse Model of Subarachnoid Hemorrhage. Mol Neurobiol 55, 2763–2779 (2018). https://doi.org/10.1007/s12035-017-0514-6

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