Intracerebral Hemorrhage and Diabetes Mellitus: Blood-Brain Barrier Disruption, Pathophysiology and Cognitive Impairments

CNS Neurol Disord Drug Targets. 2021;20(4):312-326. doi: 10.2174/1871527320666210223145112.


There is a surge in diabetes incidence, with an estimated 463 million individuals been diagnosed worldwide. Diabetes Mellitus (DM) is a major stroke-related comorbid condition that increases the susceptibility of disabling post-stroke outcomes. Although less common, intracerebral hemorrhage (ICH) is the most dramatic subtype of stroke associated with higher mortality, particularly in the DM population. Previous studies have focused mainly on the impact of DM on ischemic stroke. Few studies have focused on the impact of DM on ICH and discussed the blood- -brain barrier disruption, brain edema, and hematoma formation. However, more recently, investigating the role of oxidative damage and Reactive Oxygen Species (ROS) production in preclinical studies involving DM-ICH animal models has gained attention. But, little is known about the correlation between neuroinflammatory processes, glial cells activation, and peripheral immune cell invasion with DM-ICH injury. DM and ICH patients experience impaired abilities in multiple cognitive domains by relatively comparable mechanisms, which could get exacerbated in the setting of comorbidities. In this review, we discuss both the pathology of DM as a comorbid condition for ICH and the potential molecular therapeutic targets for the clinical management of the ICH and its recovery.

Keywords: DM; HMGB1.; ICH; blood-brain barrier; brain edema; neuroinflammation; oxidative stress; peripheral leukocytes.

Publication types

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

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiopathology*
  • Cerebral Hemorrhage / physiopathology*
  • Cognitive Dysfunction / physiopathology*
  • Diabetes Mellitus / physiopathology*
  • Disease Models, Animal
  • Humans
  • Oxidative Stress
  • Reactive Oxygen Species


  • Reactive Oxygen Species