Physiologic Reelin does not play a strong role in protection against acute stroke

Courtney Lane-Donovan, Charisma Desai, Theresa Pohlkamp, Erik J. Plautz, Joachim Herz, Ann M. Stowe

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Stroke and Alzheimer's disease, two diseases that disproportionately affect the aging population, share a subset of pathological findings and risk factors. The primary genetic risk factor after age for late-onset Alzheimer's disease, ApoE4, has also been shown to increase stroke risk and the incidence of post-stroke dementia. One mechanism by which ApoE4 contributes to disease is by inducing in neurons a resistance to Reelin, a neuromodulator that enhances synaptic function. Previous studies in Reelin knockout mice suggest a role for Reelin in protection against stroke; however, these studies were limited by the developmental requirement for Reelin in neuronal migration. To address the question of the effect of Reelin loss on stroke susceptibility in an architecturally normal brain, we utilized a novel mouse with induced genetic reduction of Reelin. We found that after transient middle cerebral artery occlusion, mice with complete adult loss of Reelin exhibited a similar level of functional deficit and extent of infarct as control mice. Together, these results suggest that physiological Reelin does not play a strong role in protection against stroke pathology.

Original languageEnglish
Pages (from-to)1295-1303
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number7
DOIs
StatePublished - Jul 1 2016

Bibliographical note

Publisher Copyright:
© The Author(s) 2016.

Funding

This work was supported by NIH grants F30AG047799 (to CLD), R37HL63762 (to JH), R01NS093382 (to JH), and R01NS088555 (to AMS), the American Health Assistance Foundation, the Consortium for Frontotemporal Dementia Research, the Bright Focus Foundation, the Lupe Murchison Foundation, the Ted Nash Long Life Foundation, the Deutsche Forschungsgemeinschaft (DFG) (grant numbers SFB 780/TP5 to JH), the American Heart Association (14SDG18410020 to AMS), and the Haggerty Center for Brain Injury and Repair (UTSW, to AMS).

FundersFunder number
Bright Focus Foundation
Consortium for Frontotemporal Dementia Research
Ted Nash Long Life Foundation
National Institutes of Health (NIH)R01NS088555, R37HL63762, R01NS093382
National Institute on AgingF30AG047799
American Health Assistance Foundation
American Heart Association14SDG18410020
Lupe Murchison Foundation
Deutsche ForschungsgemeinschaftSFB 780/TP5

    Keywords

    • ApoE4
    • Reelin
    • Reelin conditional knockout
    • stroke
    • transient middle cerebral artery occlusion

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine

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