title: 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.
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Theo
authors.initials: T
authors.lastname: Diamandis
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gonzales-Portillo
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Gonzales-Portillo
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Staples
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Mia C
authors.initials: MC
authors.lastname: Borlongan
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Hernandez
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Acosta
authors.affiliation: Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D018955:CD36 Antigens / Q000276:immunology / Q000378:metabolism*; D003919:Diabetes Insipidus / Q000150:complications*; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008954:Models, Biological; D051381:Rats
chemical_list: D015415:Biomarkers; D018955:CD36 Antigens; D008077:Lipoproteins, LDL
references.citation: Neuroscience. 2010 Dec 29;171(4):1273-82
references.pmid: 20950674
references.citation: J Neurol Neurosurg Psychiatry. 2003 Mar;74(3):312-6
references.pmid: 12588914
references.citation: Pituitary. 2005;8(3-4):251-4
references.pmid: 16508710
references.citation: J Pept Sci. 2004 May;10(5):229-48
references.pmid: 15160835
references.citation: Cell. 1998 Apr 17;93(2):241-52
references.pmid: 9568716
references.citation: Eur J Endocrinol. 2005 Mar;152(3):371-7
references.pmid: 15757853
references.citation: J Exp Med. 2003 Jun 16;197(12):1657-66
references.pmid: 12796468
references.citation: Acta Neurochir (Wien). 2001;143(3):287-95
references.pmid: 11460917
references.citation: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1481-7
references.pmid: 19608973
references.citation: Neurocrit Care. 2006;5(1):61-70
references.pmid: 16960299
references.citation: Brain Res. 2009 Sep 1;1287:157-63
references.pmid: 19573519
references.citation: J Cereb Blood Flow Metab. 2003 Feb;23(2):166-80
references.pmid: 12571448
references.citation: J Clin Endocrinol Metab. 2004 Dec;89(12):5987-92
references.pmid: 15579748
references.citation: J Neurochem. 2009 May;109 Suppl 1:126-32
references.pmid: 19393018
references.citation: J Clin Invest. 2001 Sep;108(6):785-91
references.pmid: 11560944
references.citation: Ann Neurol. 2012 Jun;71(6):753-64
references.pmid: 22718544
references.citation: Cell Med. 2012;4(2):55-63
references.pmid: 23101029
references.citation: J Trauma. 1976 Dec;16(12):979-84
references.pmid: 1003587
references.citation: Nat Med. 2001 Jul;7(7):840-6
references.pmid: 11433350
references.citation: Peptides. 2011 Jan;32(1):80-5
references.pmid: 20932867
references.citation: Neurosurgery. 2008 May;62(5):1080-93; discussion 1093-4
references.pmid: 18580806
references.citation: J Cell Mol Med. 2010 Dec;14(12):2790-802
references.pmid: 19818091
references.citation: Brain Res. 2003 Sep 26;985(2):198-201
references.pmid: 12967724
references.citation: J Biol Chem. 2010 Mar 12;285(11):8492-506
references.pmid: 20075072
references.citation: Clin Endocrinol (Oxf). 2013 Jan;78(1):17-20
references.pmid: 22891644
references.citation: PLoS One. 2013;8(1):e53376
references.pmid: 23301065
references.citation: Nat Genet. 1999 Jan;21(1):76-83
references.pmid: 9916795
references.citation: Ann Neurol. 2011 Sep;70(3):374-83
references.pmid: 21710619
references.citation: Front Neurol. 2013 Mar 04;4:18
references.pmid: 23459929
references.citation: J Neurosurg Anesthesiol. 2006 Jan;18(1):57-63
references.pmid: 16369141
references.citation: PLoS One. 2012;7(1):e30756
references.pmid: 22292032
references.citation: Atherosclerosis. 2010 Sep;212(1):153-60
references.pmid: 20684828
references.citation: J Clin Endocrinol Metab. 2000 Apr;85(4):1353-61
references.pmid: 10770165
references.citation: J Neurotrauma. 2004 Jun;21(6):685-96
references.pmid: 15253797
references.citation: Front Neurol. 2013 Mar 26;4:30
references.pmid: 23531681
references.citation: Curr Opin Lipidol. 2000 Oct;11(5):483-91
references.pmid: 11048891
references.citation: J Clin Endocrinol Metab. 2012 May;97(5):1423-33
references.pmid: 22362821
references.citation: J Neurotrauma. 2013 Dec 1;30(23):1983-90
references.pmid: 23862570
references.citation: Curr Pharm Des. 2012;18(25):3721-30
references.pmid: 22574985
references.citation: Cleve Clin J Med. 2006 Jan;73(1):65-71
references.pmid: 16444918
references.citation: J Biol Chem. 2002 Dec 6;277(49):47373-9
references.pmid: 12239221
references.citation: Atherosclerosis. 2010 Nov;213(1):129-34
references.pmid: 20701912
references.citation: J Neuroinflammation. 2012 Aug 01;9:185
references.pmid: 22849382