Type-I diabetes aggravates post-hemorrhagic stroke cognitive impairment by augmenting oxidative stress and neuroinflammation in mice

Neurochem Int. 2021 Oct:149:105151. doi: 10.1016/j.neuint.2021.105151. Epub 2021 Aug 1.


Diabetes Mellitus (DM) is a major comorbid condition that increases susceptibility to stroke. Intracerebral hemorrhage (ICH), a devastating type of stroke, accounts for only 13% of the total stroke cases but is associated with higher mortality. Multimorbid models of DM and ischemic stroke have been widely studied; however, fewer pieces of evidence are available on the impact of DM on the outcomes of ICH injury. In this study, we investigated the effect of DM on ICH-induced injury and cognitive impairments. Streptozotocin (STZ) induced type-I DM (T1DM) animal model was used, and experimental ICH was induced by intrastriatal injection of collagenase. Our results demonstrated that DM is associated with a significant increase in hematoma volume and deficits in post-stroke locomotor, sensorimotor, and cognitive behavior in mice. The levels of neuroinflammation, oxidative/nitrosative stress, and glial cell activation were also increased in the diabetic mice following ICH injury. This study provides a better understanding of the influence of DM comorbidity on hemorrhagic stroke outcomes and uncovers the important pathological mechanisms underlying DM-induced exacerbation of ICH injury.

Keywords: Cognitive impairment; Diabetes; HMGB1; ICH; Neuroinflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / metabolism*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / metabolism*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / metabolism*
  • Hand Strength / physiology
  • Inflammation Mediators / metabolism
  • Locomotion / drug effects
  • Locomotion / physiology
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / physiology*
  • Streptozocin / toxicity
  • Stroke / chemically induced
  • Stroke / metabolism*


  • Inflammation Mediators
  • Streptozocin