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

Journal

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
Volume 20, Issue 4, Pages 312-326

Publisher

BENTHAM SCIENCE PUBL
DOI: 10.2174/1871527320666210223145112

Keywords

ICH; DM; blood-brain barrier; neuroinflammation; oxidative stress; brain edema; peripheral leukocytes; HMGB1; cognitive impairment; BDNF

Funding

  1. American Heart Association [17AIREA33700076/ZAS/2017]
  2. National Institute of Neurological Disorders And Stroke of the National Institutes of Health [R01NS112642]

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Diabetes Mellitus (DM) is a major risk factor for stroke-related disabilities, especially in cases of intracerebral hemorrhage (ICH). While previous studies have focused on the impact of DM on ischemic stroke, recent attention has shifted to its effects on ICH, including oxidative damage, Reactive Oxygen Species (ROS) production, and neuroinflammatory processes in DM-ICH patients.
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.

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