Age-related murine hippocampal CA1 laminae oxidative stress measured in vivo by QUEnch-assiSTed (QUEST) MRI: impact of isoflurane anesthesia

Author:

Berkowitz Bruce A.,Podolsky Robert H.,Childers Karen Lins,Gow Alexander,Schneider Brandy L.,Lloyd Scott C.,Bosse Kelly E.,Conti Alana C.,Roberts Robin,Berri Ali M.,Graffice Emma,Sinan Kenan,Eliwat Waleed,Shen Yimin

Abstract

AbstractAge-related impairments in spatial learning and memory often precede non-familial neurodegenerative disease. Ex vivo studies suggest that physiologic age-related oxidative stress in hippocampus area CA1 may contribute to prodromal spatial disorientation and to morbidity. Yet, conventional blood or cerebrospinal fluid assays appear insufficient for early detection or management of oxidative stress within CA1 sub-regions in vivo. Here, we address this biomarker problem using a non-invasive MRI index of CA1 laminae oxidative stress based on reduction in R1 (= 1/T1) after anti-oxidant administration. An R1 reduction reflects quenching of continuous and excessive production of endogenous paramagnetic free radicals. Careful motion-correction image acquisition, and avoiding repeated exposure to isoflurane, facilitates detection of hippocampus CA1 laminae oxidative stress with QUEnch-assiSTed (QUEST) MRI. Intriguingly, age- and isoflurane-related oxidative stress is localized to the stratum lacunosum of the CA1 region. Our data raise the possibility of using QUEST MRI and FDA-approved anti-oxidants to remediate spatial disorientation and later neurodegeneration with age in animals and humans.

Funder

National Institute of Neurological Disorders and Stroke

National Eye Institute

National Institute on Aging

National Multiple Sclerosis Society

Wayne State University

Publisher

Springer Science and Business Media LLC

Subject

Geriatrics and Gerontology,Aging

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