The need to incorporate aged animals into the preclinical modeling of neurological conditions

Mujun Sun; Stuart J McDonald; Rhys D Brady; Lyndsey Collins-Praino; Glenn R Yamakawa; Mastura Monif; Terence J O'Brien; Geoffrey C Cloud; Christopher G Sobey; Richelle Mychasiuk; David J Loane; Sandy R Shultz

doi:10.1016/j.neubiorev.2019.12.027

The need to incorporate aged animals into the preclinical modeling of neurological conditions

Neurosci Biobehav Rev. 2020 Feb:109:114-128. doi: 10.1016/j.neubiorev.2019.12.027. Epub 2019 Dec 23.

Affiliations

¹ Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia.
² Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.
³ Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC 3052, Australia.
⁴ Department of Medical Sciences, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia.
⁵ Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC 3052, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia.
⁶ Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Stroke Services, Alfred Hospital, Melbourne, VIC 3004, Australia.
⁷ Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.
⁸ Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin 2, Ireland.
⁹ Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC 3052, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia. Electronic address: sandy.shultz@monash.edu.

PMID: 31877345
DOI: 10.1016/j.neubiorev.2019.12.027

Abstract

Neurological conditions such as traumatic brain injury, stroke, Parkinson's disease, epilepsy, multiple sclerosis, and Alzheimer's disease are serious clinical problems that affect millions of people worldwide. The majority of clinical trials for these common conditions have failed, and there is a critical need to understand why treatments in preclinical animal models do not translate to patients. Many patients with these conditions are middle-aged or older, however, the majority of preclinical studies have used only young-adult animals. Considering that aging involves biological changes that are relevant to the pathobiology of neurological diseases, the lack of aged subjects in preclinical research could contribute to translational failures. This paper details how aging affects biological processes involved in neurological conditions, and reviews aging research in the context of traumatic brain injury, stroke, Parkinson's disease, epilepsy, multiple sclerosis, and Alzheimer's disease. We conclude that aging is an important, but often overlooked, factor that influences biology and outcomes in neurological conditions, and provide suggestions to improve our understanding and treatment of these diseases in aged patients.

Keywords: Alzheimer’s disease; Cerebrovascular; DNA damage; Epilepsy; Immune response; Mitochondrial function; Multiple sclerosis (MS); Oxidative stress; Parkinson’s disease; Protein dysregulation; Stroke; Traumatic brain injury (TBI).

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Aging* / immunology
Aging* / metabolism
Animals
Disease Models, Animal*
Nervous System Diseases* / immunology
Nervous System Diseases* / metabolism
Nervous System Diseases* / therapy
Translational Research, Biomedical / standards*