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CADASIL and Animal Models

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White Matter Injury in Stroke and CNS Disease

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR,volume 4))

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Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common cause of inherited stroke and vascular dementia in young and middle-aged adults. The wide and heterogeneous clinical spectrum ranges from migraine with aura to leukoaraiosis and subcortical lacunar strokes, and mood disturbances, apathy and cognitive impairments. Since its genetic definition in early 1990s, an increasing number of clinical and experimental studies aimed to elucidate the relationship between CADASIL mutations on NOTCH3 gene and the pathology, aided by the development of transgenic mouse models expressing CADASIL mutations as experimental tools. In this chapter, we provide a brief review of animal models of CADASIL with an emphasis on neuropathological consequences including white matter disease.

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Abbreviations

BBB:

Blood–brain barrier

CADASIL:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

CBF:

Cerebral blood flow

CVR:

Cerebrovascular resistance

EGF:

Epidermal growth factor

MCAo:

Middle cerebral artery occlusion

N3KO:

Notch3 knockout

Notch3ECD :

Notch3 extracellular domain

NOTCH3ICD :

Notch3 intracellular domain

PID:

Peri-infarct depolarization

SD:

Spreading depression

SVD:

Small vessel disease

WT:

Wild type

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Acknowledgements

 This work was supported by the National Institutes of Health (NS055104, NS061505, NS33335), Leducq Foundation (2012D000293), Neuroendovascular Research Fund from the Andrew David Heitman Foundation, and The Ellison Foundation.

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Authors and Affiliations

  1. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 6401, Charlestown, MA, 02129, USA

    Francesco Blasi Pharm. D., Ph.D.

  2. Stroke Research Center, Massachusetts General Hospital, 175 Cambridge St., Suite 300, Boston, MA, 02114, USA

    Anand Viswanathan M.D., Ph.D.

  3. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, 149 13th Street, Room 6408, Charlestown, MA, 02129, USA

    Cenk Ayata M.D.

  4. Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    Cenk Ayata M.D.

Authors
  1. Francesco Blasi Pharm. D., Ph.D.
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  2. Anand Viswanathan M.D., Ph.D.
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  3. Cenk Ayata M.D.
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Corresponding author

Correspondence to Cenk Ayata M.D. .

Editor information

Editors and Affiliations

  1. Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA

    Selva Baltan

  2. Department of Neurology, University of California, Los Angeles, Los Angeles, California, USA

    S. Thomas Carmichael

  3. Departamento de Neurociencias, Achucarro Basque Centger for Neuroscience, University del Pais Vasco (UPV/EHU), and Centro de, Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Leioa, Spain

    Carlos Matute

  4. University of Michigan Dept. Neurosurgery, Ann Arbor, Michigan, USA

    Guohua Xi

  5. Dept. Pharmacology Dept. Neurosurgery, Loma Linda University Dept. Physiology, Loma Linda, California, USA

    John H Zhang

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Blasi, F., Viswanathan, A., Ayata, C. (2014). CADASIL and Animal Models. In: Baltan, S., Carmichael, S., Matute, C., Xi, G., Zhang, J. (eds) White Matter Injury in Stroke and CNS Disease. Springer Series in Translational Stroke Research, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9123-1_3

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  • DOI: https://doi.org/10.1007/978-1-4614-9123-1_3

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