Elsevier

Medical Hypotheses

Volume 82, Issue 2, February 2014, Pages 171-174
Medical Hypotheses

Insulin-associated neuroinflammatory pathways as therapeutic targets for traumatic brain injury

https://doi.org/10.1016/j.mehy.2013.11.028Get rights and content

Abstract

Traumatic brain injury (TBI) is characterized by an abrupt blow or exchange of force against the head and can be categorized as mild, moderate, and severe. The secondary cell death after TBI displays ischemic-like patterns including neuroinflammation. The scavenger receptor cluster of differentiation (CD) 36 is a lipid-associated protein capable of transducing intracellular signals to promote inflammatory mechanisms within different cell types. Expression and activation of CD36 is closely related to dyslipidemia secondary to diabetes. Diabetes mellitus (DM) has been documented as a co-morbidity factor in TBI, in that patients with a history of diabetes present with more severe brain damage and slower recovery from TBI than non-diabetic patients. Indeed, a strict regulation of blood serum glucose by the use of insulin promotes a better outcome for TBI patients. Based on these recent findings, we now advance the hypothesis that CD36 via DM insulin-associated pathways is closely involved in TBI chronic pathology.

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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    Both authors contributed equally.

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