Insulin-associated neuroinflammatory pathways as therapeutic targets for traumatic brain injury
Section snippets
Societal impact of traumatic brain injury
Every year in the US, 1.7 million people bear a traumatic brain injury (TBI); from which 275,000 are hospitalized and 52,000 die [1]. Overall incidence of TBI in the US is estimated to be 506.4 cases for every 100,000 [2]. Of note, armed troops deployed in Afghanistan and Iraq, are exposed to blast-induced TBI. This type of TBI has been commonly said to be a “signature wound” continuously increasing among the military population [3], [4]. Scarce data about the impact of TBI in low and
CD36-mediated neuroinflammation in TBI
The secondary cell death triggered by TBI displays ischemic-like patterns including neuroinflammation [6]. Neuroinflammation is said to be a “double-edged sword”, capable of eliciting both damaging and reparative effects [7]. The physiologic goal of inflammation is to draft diverse immune cell types into the site of the injury to remove damaged tissue and cellular debris allowing further creation of scar tissue. Microglia is the main immune cell type within the central nervous system (CNS).
Diabetes promotes a cyclic neuroinflammatory process in the brain by OxLDL crosstalk with CD36
Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both [22]. In North American countries, the prevalence for DM has been estimated to be 8.7%, 9.2% and 11.3% of all the Canadians, Mexicans and U.S. Citizens over 20 years of age, respectively. The pathology is considered a significant health issue [23], [24], [25]. “Diabetic dyslipidemia” is a term used to refer to the abnormal levels of lipids and
Hypothesis
DM patients diagnosed with TBI have a higher mortality along with a longer hospital stay, lower Glasgow comma scale values, and higher injury severity scores [52]. Changes in glucose levels are well known to occur in the CNS following TBI [53] and indeed secondary brain injury management requires aggressive control of the metabolic supply into the brain [54]. Although many of these parameters have been related to the progression of TBI, much of the interactions between these values are yet to
Funding support
CVB is supported by NIH NINDS 1R01NS071956–01, Department of Defense W81XWH1110634, James and Esther King Foundation for Biomedical Research Program 1KG01–33966, SanBio Inc., Celgene Cellular Therapeutics, KMPHC and NeuralStem Inc.
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Cited by (9)
Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment
2022, Pharmacological ResearchCitation Excerpt :Furthermore, brain glucose metabolism is dramatically altered following a TBI, with an acute increase in cerebral glucose metabolism typically followed by an extended decline in glucose metabolism [71]. Aligned with this, there are multiple reports of hyperglycemia following TBI, with uncontrolled blood glucose levels resulting in poorer outcomes for recovery and an increased mortality risk [72–74]. IR is a marker of increased risk for ischemic stroke [75] and, additionally, is associated with poorer functional outcomes [76].
Insulin in the Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
2020, World NeurosurgeryCitation Excerpt :A member of this latter group of compounds is being evaluated in the STEXAS (Short-Term Exenatide Therapy in Acute Ischaemic Stroke) trial.36 Alternatively, pathways associated with insulin have been proposed as potential therapeutic targets for secondary brain injury associated with hyperglycemia.37,38 The findings of this meta-analysis are, therefore, timely and sobering.
Astrocyte-targeted Overproduction of IL-10 Reduces Neurodegeneration after TBI
2022, Experimental NeurobiologyLutein protects against severe traumatic brain injury through anti-inflammation and antioxidative effects via ICAM-1/Nrf-2
2017, Molecular Medicine Reports
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Both authors contributed equally.