Vascular Mechanisms in CNS Trauma

523 Pages·2014·6.383 MB·English

by  Adam Chodobski, Brian J. Zink, Joanna Szmydynger-Chodobska (auth.), Eng H. Lo, Josephine Lok, MingMing Ning, Michael J. Whalen (eds.)

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
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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