Diabetes insipidus contributes to traumatic brain injury pathology via CD36 neuroinflammation

Abstract

Each year, over one million people in the United States are affected by traumatic brain injury (TBI). Symptoms of both acute and chronic neuroinflammation follow TBI, coinciding with a robust immune response and activation of the brain's endogenous repair mechanisms. TBI can lead to endocrine failure as a result of damage to the thalamic region of the brain, evidenced by excessive thirst and polyuria often accompanying TBI. These symptoms indicate the presence of diabetes insipidus (DI), a disruption of water homeostasis due to antidiuretic hormone deficiency. This deficiency accompanies a mechanical or neuroinflammatory damage to the thalamic region during TBI, evidenced by increased expression of inflammatory microglial marker MHCII in this brain region. Excessive thirst and urinations, which are typical DI symptoms, in our chronic TBI rats also suggest a close connection between TBI and DI. We seek to bridge this gap between TBI and DI through investigation of the Cluster of Differentiation 36 (CD36) receptor. This receptor is associated with Low-Density Lipoprotein (LDL) deregulation, pro-inflammatory events, and innate immunity regulation. We posit that CD36 exacerbates TBI through immune activation and subsequent neuroinflammation. Indeed, scientific evidence already supports pathological interaction of CD36 in other neurological disorders including stroke and Alzheimer's disease. We propose that DI contributes to TBI pathology via CD36 neuroinflammation. Use of CD36 as a biomarker may provide insights into treatment and disease pathology of TBI and DI. This unexplored avenue of research holds potential for a better understanding and treatment of TBI and DI.

Figure 1. CD36 neuroinflammation in the thalamic/hypothalamic region - a pathological link between DI and TBI

(A). This picture depicts a brain that has suffered TBI, demonstrating a modest level of inflammation. (B). A person who suffers from diabetes insipidus has more ligands available that activate CD36, consequently causing more inflammation.

Figure 2. CD36 expression in TBI rat brain

A representative microphotograph (20x) showing activated microglial cells in the thalamus/hypothalamus of an animal subjected at 30 days post-injury after controlled cortical impact model of TBI. MHCII+ stained cells (black arrows in A), with adjacent coronal section demonstrating CD36+ (white arrows in B).