Vascular Mechanisms in CNS Trauma PDF
Preview Vascular Mechanisms in CNS Trauma
Springer Series in Translational Stroke Research Eng H. Lo Josephine Lok MingMing Ning Michael J. Whalen Editors Vascular Mechanisms in CNS Trauma Springer Series in Translational Stroke Research SeriesEditor JohnZhang For furthervolumes: http://www.springer.com/series/10064 . Eng H. Lo (cid:129) Josephine Lok (cid:129) MingMing Ning (cid:129) Michael J. Whalen Editors Vascular Mechanisms in CNS Trauma Editors EngH.Lo JosephineLok DepartmentsofNeurology DepartmentofPediatrics andRadiology MassachusettsGeneralHospital MassachusettsGeneralHospital HarvardMedicalSchool HarvardMedicalSchool Boston,MA,USA Boston,MA,USA MingMingNing MichaelJ.Whalen DepartmentofNeurology DepartmentofPediatrics MassachusettsGeneralHospital MassachusettsGeneralHospital HarvardMedicalSchool HarvardMedicalSchool Boston,MA,USA Boston,MA,USA ISBN978-1-4614-8689-3 ISBN978-1-4614-8690-9(eBook) DOI10.1007/978-1-4614-8690-9 SpringerNewYorkHeidelbergDordrechtLondon LibraryofCongressControlNumber:2013953546 ©SpringerScience+BusinessMediaNewYork2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped.Exemptedfromthislegalreservationarebriefexcerpts inconnectionwithreviewsorscholarlyanalysisormaterialsuppliedspecificallyforthepurposeofbeing enteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.Duplication ofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheCopyrightLawofthe Publisher’s location, in its current version, and permission for use must always be obtained from Springer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyrightClearanceCenter. ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Foreword Recognizingthatthemodernhistoryofthestudyoftraumaticbrainandspinalcord injury has spanned less than 50 years, it is not surprising that our current under- standing of the pathobiology and treatment of these devastating neurological disorders remains incomplete and in some cases, controversial. When first addressed in the early 1970s, the focus of neurotrauma research took a distinct vascularfocus,withmanybelievingthatthemostimportantmechanismunderlying the morbidity associated with CNS injury was the occurrence of traumatically induced vasogenic edema. It was assumed that the mechanical forces of injury disruptedtheblood–brainbarrierleadingtotheextravasationofserumproteinsand other damaging agents capable of recruiting increased water within the central nervoussystemtherebyelevatingintra-parenchymal/intracranialpressure.Further, itwasassumedthatthiselevatedpressurealonetriggeredallthedamagingcascades of injury associated with tissue compression and subsequent CNS tissue damage. Otherssuggestedthatthesameforcesofinjuryalteredvascularfunctionleadingto impaired autoregulation and/or impaired vasoreactivity to normal physiological challenges, predisposing the CNS to further injury when a secondary insult, such ashypoxia orhypotension ensued. This early vascularfocus was solidified by the recognitionthatthesameforcesofinjury,particularlythoseonthemoresevereend of the spectrum,invariably caused overt vascular damage reflected inlocalspinal cord hemorrhage followed by tissue cavitation or the occurrence of hemorrhagic contusionalchangewithinthecerebralcortex.Inpart,becauseofthefailureofearly clinical trials targeting vascular mechanisms to achieve therapeutic benefit and in part, due to the frustration of some over this vascular-dominated approach to neurotrauma research, the subsequent 2–3 decades of neurotrauma discovery took a decidedly neuronal centric focus. During this period, there was a dramatic shift in neurotrauma research to the considerations of altered neurotransmission/ neuroexcitation, neuronal cell death framed in the context of apoptosis versus necrosis, axonal dysfunction and disconnection, and the sequelae of such discon- nection in terms of CNS tissue deafferentation and neuroplastic change. These neuronal focused studies were interfaced with parallel metabolic, behavioral, and targeted therapeutic studies conducted both in animals and humans who had v vi Foreword sustained traumatic injury to either the brain or spinal cord. Unfortunately, as appreciated by all, this period of discovery, although highly significant, also failed to generate a full understanding of the pathobiology of CNS injury and/or lead to the development of more rational therapeutic approaches to improve outcomeinthosewhohavesustainedtraumaticinjurytoeitherthebrainorspinal cord. In light of these limitations and clinical trial failures, the last decade has witnessed a more integrative approach, coupling the interaction of the CNS and itsintrinsicvasculature,tobetterunderstandtheoverallpathogenesisofCNSinjury and its potential therapeutic targeting. Now framed in the context of the neurovascular unit, contemporary research has begun to focus on the cell-specific responses therein while also exploring the various complex interactions between these neuronal vascular and their related glial pathways. In this context, renewed emphasis has been placed on the understanding of the blood–brain/blood-spinal cord barrier, not only in terms of its alteration following traumatic insult but also inthecontextofitsabilitytomodulatenutrienttransportaswellasthepassageof variouspurportedneuroprotectiveagents. Againstthisbackdropofdiscovery,thecurrenttexteditedbyLoandcolleagues framesourcontemporaryunderstandingofthevascularsequelaeoftraumaticinjury to the CNS in an effort to achieve a more comprehensive understanding of CNS/neuronal responses to injury. The 29 chapters contained therein provide important insight into the complex and diverse vascular changes associated with traumaticCNSinjury,withagoodmixofbothbasicscienceandclinicaldiscovery. Theauthors who have participated inthegeneration ofthis bookprovidedetailed insight into virtually all of the important components of the vascular sequelae of injury and their CNS/neuronal interactions. The chapters in this text focus on important themes considering traumatically altered cerebral blood flow, autoregulation, vasoreactivity, coagulation, and blood–brain barrier status, while alsoaddressingtheimportanceoftheneuronal/glialvascularunit.Thesestudiesare complemented by parallel considerations of more contemporary diagnostic and therapeuticapproachesrangingfromtheuseofproteomicsandadvancedimaging tothemoderntoolsofelectrophysiologyandmicrodialysis-basedassessment. Collectively,theeditorsandauthorsaretobecongratulatedontheirsuccessin producingthisimportanttext.Itwillserveasaninvaluablereferenceforthosefirst enteringthefieldaswellastheseasonedinvestigatorwhowishestoupdatehisor her understanding of the complex vascular sequelae associated with traumatic injurytothecentralnervoussystem. Richmond,VA JohnT.Povlishock,PhD Preface Thevasculatureofthecentralnervoussystemperformsthevitaltasksofperfusing the brain and spinal cord, and maintaining barrier functions that ensure a proper environment for neuronal activity. Additionally, the vasculature participates in otherkeyfunctions,including theproductionofvasoconstrictingandvasodilating substances,theprovisionoftrophicsupporttotheneuronalandglialparenchyma, the response to inflammatory stimuli, and the regulation of tissue remodeling and repair after injury. Hence, a rigorous understanding of vascular mechanisms is essential for the development of therapeutic strategies for brain and spinal cord trauma. Itisnowanopportunetimetoincorporatethestudyofthevasculatureinthefield of CNS trauma science. Our hope in putting together this book is to provide a referenceforcliniciansandresearcherswhoareundertakingfurtherexplorationsof theCNSvasculaturewithinthecomplexpathophysiologyofinjuryanddisease.We dedicate this book to investigators who are studying ways to treat patients and to improve the lives of survivors of brain and spinal cord trauma. And most impor- tantly,wethankthemanypatientsandfamilieswhoseeffortstoreclaimtheirlives afterCNStraumaprovidetheinspirationforourwork. Boston,MA EngH.Lo Boston,MA JosephineLok Boston,MA MingMingNing Boston,MA MichaelJ.Whalen vii . Contents PartI MolecularMechanisms 1 CNSBarriersinNeurotrauma. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 AdamChodobski,BrianJ.Zink,andJoannaSzmydynger-Chodobska 2 MechanismsofCerebralEdemaLeadingtoEarlySeizures AfterTraumaticBrainInjury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 PhilipH.IfflandII,GeraldA.Grant,andDamirJanigro 3 HumanCerebralBloodFlowandTraumaticBrainInjury. . . . . . . 47 DavidA.HovdaandThomasC.Glenn 4 GliovascularTargetsinTraumaticCNSInjury. . . . . . . . . . . . . . . 55 ArjunKhanna,BrianP.Walcott,KristopherT.Kahle, VolodymyrGerzanich,andJ.MarcSimard 5 NeurovascularResponsestoTraumaticBrainInjury. . . . . . . . . . . 75 JosephineLok,KenArai,Shu-zhenGuo,WendyLeung,TakakuniMaki, DeeptiNavaratna,KlausvanLeyen,ChanghongXing,LiminWu, NatanNoviski,andEngH.Lo 6 TheEffectsofIntravascularCoagulationandMicrothrombosis onCerebralPerfusionAfterBrainTrauma. . . . . . . . . . . . . . . . . . 105 MonishaA.Kumar,DouglasH.Smith,andShermanC.Stein 7 BarrierstoDrugDeliveryforBrainTrauma. . . . . . . . . . . . . . . . . 125 F.AnthonyWillyerd,PhilipE.Empey,PatrickM.Kochanek, andRobertS.B.Clark 8 AngiogenesisandFunctionalRecoveryAfterTraumatic BrainInjury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 YanluZhang,YeXiong,AsimMahmood,ZhengGangZhang, andMichaelChopp ix
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