Cerebral ischemic damage in diabetes: an inflammatory perspective

Abstract

Stroke is one of the leading causes of death worldwide. A strong inflammatory response characterized by activation and release of cytokines, chemokines, adhesion molecules, and proteolytic enzymes contributes to brain damage following stroke. Stroke outcomes are worse among diabetics, resulting in increased mortality and disabilities. Diabetes involves chronic inflammation manifested by reactive oxygen species generation, expression of proinflammatory cytokines, and activation/expression of other inflammatory mediators. It appears that increased proinflammatory processes due to diabetes are further accelerated after cerebral ischemia, leading to increased ischemic damage. Hypoglycemia is an intrinsic side effect owing to glucose-lowering therapy in diabetics, and is known to induce proinflammatory changes as well as exacerbate cerebral damage in experimental stroke. Here, we present a review of available literature on the contribution of neuroinflammation to increased cerebral ischemic damage in diabetics. We also describe the role of hypoglycemia in neuroinflammation and cerebral ischemic damage in diabetics. Understanding the role of neuroinflammatory mechanisms in worsening stroke outcome in diabetics may help limit ischemic brain injury and improve clinical outcomes.

Hyperglycemia‐Triggered Sphingosine‐1‐Phosphate and Sphingosine‐1‐Phosphate Receptor 3 Signaling Worsens Liver Ischemia/Reperfusion Injury by Regulating M1/M2 Polarization

“…Overwhelming epidemiological and clinical data have demonstrated that patients with DM are more sensitive to IRI . Diabetes and its associated hyperglycemia are involved in a variety of ischemic tissue injuries, including in the lungs, brain, kidney, and liver . The numerous functions of S1P include the regulation of cell death, proliferation, motility, differentiation, and inflammation .…”

“…(28) Diabetes and its associated hyperglycemia are involved in a variety of ischemic tissue injuries, including in the lungs, brain, kidney, and liver. (29)(30)(31)(32) The numerous functions of S1P include the regulation of cell death, proliferation, motility, differentiation, and inf lammation. (33)(34)(35) Most of the effects of S1P are mediated through the S1PR family, which includes the ubiquitously expressed S1PR1, S1PR2, and S1PR3 subtypes.…”

Interaction of diabetes and smoking on stroke: A population-based cross-sectional survey in China

“…The pathophysiological mechanisms of hyperglycemia induce oxidative stress; promote formation of advanced glycosylation end products; 40,41 increase blood–brain barrier permeability and inflammatory responses; 42 lead to accumulation of reactive oxygen species/reactive nitrogen, inflammation, and mitochondrial dysfunction; 43 lead to cellular dysfunction; damage vascular tissue; inhibit endogenous vascular protective factors; alter vascular homeostasis; 44 raise levels of reactive oxygen species and advanced glycation end products; decrease levels of mitochondrial superoxide dismutase; 41 and correlate with endothelial cell dysfunction and nitric oxide production. 45 All these actions contribute to accelerating the atherosclerotic process.…”

Chronic Cerebral Ischemia-Induced Memory Impairment After Inhibition of BDNF by Interleukin-1 Signaling Pathway

“…[8][9]. Besides, a series of damage mechanisms such as glial cell activation, increased or decreased neurotransmitters, activation of oxidative stress, and neuro immunization which all play a critical role in the development of Bins-wanger disease, Alzheimer's disease (AD), Vascular dementia (VD) and so on, are involved under chronic cerebral ischemia [10][11]. Microglia of neuroprotective and neurotoxic properties are now generally considered as immunological cells widely distributed in the central nervous system.…”