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brain sciences Review OverviewofTraumaticBrainInjury: AnImmunologicalContext DamirNizamutdinov1,2 andLeeA.Shapiro1,2,* 1 DepartmentofSurgery,TexasA&MUniversityHealthScienceCenter,CollegeofMedicine,Temple, TX76504,USA;dnizamutdinov@medicine.tamhsc.edu 2 DepartmentofNeurosurgery,NeuroscienceResearchInstitute,BaylorScott&WhiteHealth,Temple, TX76504,USA * Correspondence: lshapiro@medicine.tamhsc.edu;Tel.:+1-254-724-6267 AcademicEditor:DonnaGruol Received: 21October2016;Accepted: 13 January2017;Published: 23 January2017 Abstract:Traumaticbrain injury(TBI)afflictspeopleofallagesandgenders,andtheseverityof injury ranges fromconcussion/mildTBI to severe TBI.Across all spectrums, TBI haswide-ranging, and variable symptomologyandoutcomes. Treatmentoptionsare lacking for theearlyneuropathology associatedwithTBIsandfor thechronicneuropathologicalandneurobehavioraldeficits. Inflammation andneuroinflammation appear to bemajormediators of TBI outcomes. These systems are being intensivelystudiesusinganimalmodelsandhumantranslationalstudies, inthehopesofunderstanding themechanismsofTBI,anddevelopingtherapeuticstrategies to improvetheoutcomesof themillions ofpeople impactedbyTBIs eachyear. Thismanuscriptprovides anoverviewof the epidemiology andoutcomes of TBI, andpresents data obtained fromanimal andhuman studies focusing on an inflammatoryandimmunologicalcontext. Suchacontext is timely,asrecentstudiesblur thetraditional understandingof an “immune-privileged” central nervous system. Inpresenting the evidence for specific,adaptive immuneresponseafterTBI, it ishopedthat futurestudieswillbe interpretedusinga broaderperspectivethat includesthecontributionsof theperipheral immunesystem, tocentralnervous systemdisorders,notablyTBIandpost-traumaticsyndromes. Keywords: traumaticbrain injury;neuroimmunity;neuroinflammation 1.TypesofTraumaticBrainInjuries inHumans 1.1. EpidemiologyofTBI in theUnitedStates Atraumaticbrain injury (TBI) isan injury thatdisrupts thenormal functionof thebrainandcan becausedbyabump,blowor jolt to thehead, rapidaccelerationanddecelerationof thecalvarium, orapenetratingheadinjury[1]. In2010, theCenters forDiseaseControlandPreventionestimatedthat TBIsaccountedforapproximately2.5millionemergencydepartment (ED)visits in theUnitedStates. Of these,approximately87%(2,213,826)were treatedandreleased,11%(283,630)werehospitalized anddischarged,andapproximately2%(52,844)died[2]. The leadingcausesofnon-fatalTBI in theU.S. are falls (35%),motorvehicle-associatedaccidents (17%)andstrikesorblowsto theheadfrom/against objects, includingsport injuries (17%) [3]. The leadingcausesofTBI-relateddeathsaremotorvehicle crashes, suicidesandfalls. In theUnitedStates, childrenaged0–4years, adolescentsaged15–19years, andolderadultsaged>75yearshavethehighestratesofTBI-relatedhospitalizationsanddeathsamong allagegroups[3].Approximately145,000children/adolescent (aged0–19years)and775,000older adults (>75years) are estimated tobe livingwith substantial and long-lasting limitations in social, behavioral,physicaland/orcognitive functioningfollowingaTBI [4]. Ineveryagegroup,TBI-related EDvisit rates arehigher formales than for females,whichwere 800.4 vs. 633.7 casesper 100,000, BrainSci. 2017,7, 11 130 www.mdpi.com/journal/brainsci