Comparison of Post-Ischemic Brain Injury in Young and Middle-Aged Stroke Rats

Stroke is a disease of the elderly, and its incidence, disability, and mortality increase with age. Age-associated comorbidity is complex; thus, the exacerbation mechanisms of stroke injury in the elderly are multifactorial. To extend the scope of relevant studies, we aimed to investigate whether age and comorbidities are associated with severe post-ischemic brain injury and identified the factors involved in a rat model of stroke. Male adult Sprague Dawley rats at the age of 12 months (middle-aged) exhibited an endogenous environment that was more conducive to hyperlipidemia, hyperglycemia, hyperinsulinemia, insulin resistance, and chronic low-grade inflammation than rats at the age of 2 months (young). Middle-aged rats suffered from greater exacerbation of brain injury following cerebral ischemia than young rats when both the common carotid and the right middle cerebral arteries were clamped. The metabolic abnormalities of rats rendered them prone to ischemic brain injury, and post-ischemic brain injury in turn further augmented deleterious metabolic abnormalities. In conclusion, our results demonstrate that age-associated comorbidities such as hyperglycemia, insulin resistance, and chronic inflammation predispose rats to cerebral ischemia injury. The mechanisms of ischemic brain injury elucidated in our model of young and middle-aged rats with stroke could serve as the basis for further studies on this condition in the elderly.