Cellular and Molecular Mechanisms Underlying Non-Pharmaceutical Ischemic Stroke Therapy in Aged Subjects

Int J Mol Sci. 2017 Dec 29;19(1):99. doi: 10.3390/ijms19010099.

Abstract

The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia. Indeed, recent results suggest that H₂S-induced hypothermia in aged, overweight rats could have a higher probability of success in treating stroke as compared to other monotherapies, by reducing post-stroke brain inflammation. Likewise, it was recently reported that weight reduction prior to stroke, in aged, overweight rats induced by caloric restriction, led to an early re-gain of weight and a significant improvement in recovery of complex sensorimotor skills, cutaneous sensitivity, or spatial memory.

Conclusion: animal models of stroke done in young animals ignore age-associated comorbidities and may explain, at least in part, the unsuccessful bench-to-bedside translation of neuroprotective strategies for ischemic stroke in aged subjects.

Keywords: ageing; calorie restriction; cerebral ischemia; hypothermia; inflammation; obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Ischemia / epidemiology
  • Brain Ischemia / etiology
  • Brain Ischemia / metabolism*
  • Brain Ischemia / therapy
  • Caloric Restriction / methods
  • Comorbidity
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / physiopathology
  • Diabetes Mellitus / therapy
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Humans
  • Hydrogen Sulfide / pharmacology
  • Hypercholesterolemia / epidemiology
  • Hypercholesterolemia / metabolism*
  • Hypercholesterolemia / physiopathology
  • Hypercholesterolemia / therapy
  • Hypertension / epidemiology
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Hypertension / therapy
  • Hypothermia, Induced / methods
  • Obesity / epidemiology
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Obesity / therapy
  • Rats
  • Sedentary Behavior
  • Stroke / epidemiology
  • Stroke / etiology
  • Stroke / metabolism*
  • Stroke / therapy

Substances

  • Hydrogen Sulfide