Changes in experimental stroke outcome across the life span

• Published in: Journal of cerebral blood flow and metabolism 2009-04, Vol.29 (4), p.792-802
• Main Authors: Liu, Fudong, Yuan, Rongwen, Benashski, Sharon E, McCullough, Louise D
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Animals; Biological and medical sciences; Blood-Brain Barrier - metabolism; Edema - etiology; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Infarction, Middle Cerebral Artery; Male; Medical sciences; Mice; Nervous system (semeiology, syndromes); Neurology; Sex Factors; Stroke - pathology; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2009.5

Acute ischemic stroke is a leading cause of mortality and disability in the elderly. Age is the most important nonmodifiable risk factor for stroke, yet many preclinical models continue to examine only young male animals. It remains unclear how experimental stroke outcomes change with aging and with biologic sex. If sex differences are present, it is not known whether these reflect an intrinsic differing sensitivity to stroke or are secondary to the loss of estrogen with aging. We subjected both young and aging mice of both sexes to middle cerebral artery occlusion (MCAO). Young female mice had smaller strokes compared with age-matched males, an effect that was reversed by ovariectomy. Stroke damage increased with aging in female mice, whereas male mice had decreased damage after MCAO. Blood–brain barrier (BBB) permeability changes are correlated with infarct size. However, aging mice had significantly less edema formation, an effect that was independent of sex and histologic damage. Differences in the cellular response to stroke occur across the life span in both male and female mice. These differences need to be considered when developing relevant therapies for stroke patients, the majority of whom are elderly.