Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

150 Pages·2014·13.65 MB·English

BioMed Research International
Cerebral Vasospasm after Aneurysmal
Subarachnoid Hemorrhage: Mechanism
and Therapies
Guest Editors: Chih-Lung Lin, Aaron S. Dumont, John H. Zhang,
Mario Zuccarello, and Carl Muroi
Cerebral Vasospasm after Aneurysmal
Subarachnoid Hemorrhage: Mechanism
and Therapies
BioMed Research International
Cerebral Vasospasm after Aneurysmal
Subarachnoid Hemorrhage: Mechanism
and Therapies
Guest Editors: Chih-Lung Lin, Aaron S. Dumont,
John H. Zhang, Mario Zuccarello, and Carl Muroi
Copyright©2014HindawiPublishingCorporation.Allrightsreserved.
Thisisaspecialissuepublishedin“BioMedResearchInternational.”AllarticlesareopenaccessarticlesdistributedundertheCreative
CommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginal
workisproperlycited.
Contents
CerebralVasospasmafterAneurysmalSubarachnoidHemorrhage:MechanismandTherapies,
Chih-LungLin,AaronS.Dumont,JohnH.Zhang,MarioZuccarello,andCarlMuroi
Volume2014,ArticleID679014,3pages
UpregulationofRelaxinafterExperimentalSubarachnoidHemorrhageinRabbits,YuichiroKikkawa,
SatoshiMatsuo,RyotaKurogi,AkiraNakamizo,MasahiroMizoguchi,andTomioSasaki
Volume2014,ArticleID836397,9pages
PatientOutcomesfollowingSubarachnoidHemorrhagebetweentheMedicalCenterandRegional
Hospital:WhetherAllPatientsShouldBeTransferredtoMedicalCenters,Tsung-YingLin,
ChiehHsinWu,Wei-CheLee,Chao-WenChen,Liang-ChiKuo,Shiuh-LinHuang,Hsing-LinLin,
andChih-LungLin
Volume2014,ArticleID927803,5pages
TheRoleofMicroclotFormationinanAcuteSubarachnoidHemorrhageModelintheRabbit,
LukasAndereggen,VolkerNeuschmelting,MichaelvonGunten,HansRudolfWidmer,JavierFandino,
andSergeMarbacher
Volume2014,ArticleID161702,10pages
TheHarmfulEffectsofSubarachnoidHemorrhageonExtracerebralOrgans,ShengChen,QianLi,
HaijianWu,PaulR.Krafft,ZhenWang,andJohnH.Zhang
Volume2014,ArticleID858496,12pages
Inflammation,Vasospasm,andBrainInjuryafterSubarachnoidHemorrhage,BrandonA.Miller,
NefizeTuran,MonicaChau,andGustavoPradilla
Volume2014,ArticleID384342,16pages
AlterationofBasilarArteryRho-KinaseandSolubleGuanylylCyclaseProteinExpressioninaRat
ModelofCerebralVasospasmfollowingSubarachnoidHemorrhage,Chih-JenWang,Pei-YuLee,
Bin-NanWu,Shu-ChuanWu,Joon-KhimLoh,Hung-PeiTsai,Chia-LiChung,NealF.Kassell,
andAij-LieKwan
Volume2014,ArticleID531508,8pages
ToLookBeyondVasospasminAneurysmalSubarachnoidHaemorrhage,GiuliaCossu,
MahmoudMesserer,MauroOddo,andRoyThomasDaniel
Volume2014,ArticleID628597,14pages
ProgesteroneAttenuatesExperimentalSubarachnoidHemorrhage-InducedVasospasmby
UpregulationofEndothelialNitricOxideSynthaseviaAktSignalingPathway,Chia-MaoChang,
Yu-FengSu,Chih-ZenChang,Chia-LiChung,Yee-JeanTsai,Joon-KhimLoh,andChih-LungLin
Volume2014,ArticleID207616,6pages
TheRoleofArteriolesandtheMicrocirculationintheDevelopmentofVasospasmafterAneurysmal
SAH,MasatoNaraoka,NaoyaMatsuda,NorihitoShimamura,KenichiroAsano,andHirokiOhkuma
Volume2014,ArticleID253746,9pages
ProphylacticIntra-ArterialInjectionofVasodilatorforAsymptomaticVasospasmConvertsthePatient
toSymptomaticVasospasmduetoSevereMicrocirculatoryImbalance,NorihitoShimamura,
MasatoNaraoka,NaoyaMatsuda,KiyohideKakuta,andHirokiOhkuma
Volume2014,ArticleID382484,7pages
ImpactofClippingversusCoilingonPostoperativeHemodynamicsandPulmonaryEdemaafter
SubarachnoidHemorrhage,NobutakaHorie,MitsutoshiIwaasa,EijiIsotani,ShunsukeIshizaka,
TooruInoue,andIzumiNagata
Volume2014,ArticleID807064,9pages
MagnesiumLithospermateB,anActiveExtractofSalviamiltiorrhiza,MediatessGC/cGMP/PKG
TranslocationinExperimentalVasospasm,Chih-ZenChang,Shu-ChuanWu,andAij-LieKwan
Volume2014,ArticleID272101,9pages
Incidence,NationalTrend,andOutcomeofNontraumaticSubarachnoidHaemorrhageinTaiwan:
InitialLowerMortality,PoorLong-TermOutcome,Hsing-LinLin,Kwan-MingSoo,Chao-WenChen,
Yen-KoLin,Tsung-YingLin,Liang-ChiKuo,Wei-CheLee,andShiuh-LinHuang
Volume2014,ArticleID274572,5pages
CerebralVasospasminPatientsover80YearsTreatedbyCoilEmbolizationforRupturedCerebral
Aneurysms,TomohitoHishikawa,YujiTakasugi,TomohisaShimizu,JunHaruma,MasafumiHiramatsu,
KojiTokunaga,KenjiSugiu,andIsaoDate
Volume2014,ArticleID253867,5pages
TherapeuticImplicationsofEstrogenforCerebralVasospasmandDelayedCerebralIschemiaInduced
byAneurysmalSubarachnoidHemorrhage,DaleDing,RobertM.Starke,AaronS.Dumont,
GaryK.Owens,DavidM.Hasan,NohraChalouhi,RickyMedel,andChih-LungLin
Volume2014,ArticleID727428,9pages
DescriptionoftheVasospasmPhenomenafollowingPerimesencephalicNonaneurysmalSubarachnoid
Hemorrhage,DaphnaPrat,OdedGoren,BelaBruk,MatiBakon,MosheHadani,andSagiHarnof
Volume2013,ArticleID371063,8pages
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 679014, 3 pages
http://dx.doi.org/10.1155/2014/679014
Editorial
Cerebral Vasospasm after Aneurysmal Subarachnoid
Hemorrhage: Mechanism and Therapies
Chih-LungLin,1,2AaronS.Dumont,3JohnH.Zhang,4MarioZuccarello,5andCarlMuroi6,7
1DepartmentofNeurosurgery,KaohsiungMedicalUniversityHospital,Kaohsiung807,Taiwan
2FacultyofMedicine,GraduateInstituteofMedicine,CollegeofMedicine,KaohsiungMedicalUniversity,Kaohsiung807,Taiwan
3DepartmentofNeurosurgery,TulaneUniversity,NewOrleans,LA70112,USA
4DepartmentsofNeurosurgery,Physiology,andAnesthesiology,LomaLindaUniversitySchoolofMedicine,LomaLinda,CA92354,
USA
5DepartmentofNeurosurgery,UniversityofCincinnati,Cincinnati,OH45219,USA
6NeurocriticalCareUnit,DepartmentofNeurosurgery,UniversityHospitalZurich,Frauenklinikstrasse10,8091Zurich,Switzerland
7DepartmentofNeurosurgery,KantonsspitalAarau,Tellstrasse,5001Aarau,Switzerland
CorrespondenceshouldbeaddressedtoChih-LungLin;[email protected]
Received13August2014;Accepted13August2014;Published8September2014
Copyright©2014Chih-LungLinetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Although cerebral vasospasm (CV) after aneurysmal sub- is presented in up to 70% of SAH patients, only 20–30% of
arachnoidhemorrhage(SAH)hasbeenrecognizedformore allSAHpatientssufferfromclinicallysymptomaticCV[3].
thanhalfacentury,itspathophysiologicmechanismremains Nonetheless, it is now evident that CV alone is inadequate
elusive [1]. Delayed CV has classically been considered as tocompletelyexplainDCIfollowinganeurismalrupture[2,
the leading and treatable cause of mortality and morbidity 4]. Recent studies on the treatment of CV have failed to
in patients following aneurysmal SAH. Despite intensive solidly support the correlation between angiogram-shown
research efforts, SAH-induced CV remains incompletely improvement in CV and prognosis. Besides, various drugs
understood from both the pathogenic and the therapeu- proveneffectiveforbetterfunctionaloutcomeshavedemon-
tic perspectives. Many pathological processes have been strated their independency of CV reduction. Currently, a
proposed to explain the pathogenesis of delayed CV after multifactorial etiology for DCI has emerged, whereas the
SAH,includingendothelialdamage,smoothmusclecontrac- role of CV has shifted from the major and most significant
tion,changinginvascularresponsiveness,andinflammatory determinant to one contributing factor, just like any other
and/or immunological response of the vascular wall [2]. At factors, to the process. The study of the pathophysiology
present, the most important and critical aspects of SAH- of DCI has become more broad-minded with several other
induced CV are its failure to consistently respond to treat- differentmechanismsbeingactivelyinvestigated.
ment and only partial success could be achieved in both The term “early brain injury” (EBI) was first postulated
experimentalmodelsandclinicaltrials. in 2004, more than 40 years after delayed CV was first
For patients with SAH surviving the early phase, sec- described, to explain the acute pathophysiological events
ondaryischemia(ordelayedcerebralischemia,DCI)ispop- occurringwithin72hoursofSAH[5,6].Theseeventsinclude
ularlyconsideredastheleadingdeterminantofpoorclinical cerebral autoregulation and blood-brain barrier disruption,
outcome.AmongstthecomplicationsafterSAH,CVhasbeen activationofinflammatorypathways,excitotoxicity,oxidative
regarded as the major cause of DCI. However, there have stress,andactivationofapoptosis[7].Thesearedirecteffects
beenanincreasingnumberofevidencessupportingmultiple ofbloodclotinthesubarachnoidspaceandalsooftransient
etiologiesofDCIotherthanCV.AlthoughradiographicCV cerebral ischemia, leading to brain injury not confined to
2 BioMedResearchInternational
Subarachnoid hemorrhage
0hours
Excitotoxicity
Cerebral autoregulation
disruption
Blood-brain barrier Early brain injury Oxidative stress activation
disruption of apoptosis
Activation of
Activation of apoptosis
inflammatory pathways
72hours
Activation of proapoptotic
pathways Arteriolar constriction
Disruption of the
Delayed cerebral ischemia Thrombosis and dysfunction
blood-brain barrier
in microcirculation
Cerebral vasospasm
Cortical spreading ischemia
Endothelial damage
Smooth muscle contraction
Change in vascular responsiveness
Inflammatory and/or immunological
Figure1:Themechanismsofearlybraininjuryanddelayedcerebralischemiafollowingsubarachnoidhemorrhage.
thesiteofhemorrhage.ManymechanismsofEBIcontribute extracerebral organs damage and long-term complications
tothepathogenesisofDCIandarehenceaccountableforthe after aneurysmal and nonaneurysmal SAH are also pre-
poor outcomes. Causes of DCI have been attributed to the sented. Medical resources utilization in patients following
combined effects of delayed CV, activation of proapoptotic SAH between the medical center and regional hospital is
pathways, disruption of the blood-brain barrier, arteriolar reportedonanationwidepopulation-basedstudy.
constriction, thrombosis and dysfunction in microcircula- DCI, a result of different pathological pathways, is a
tion, and cortical spreading ischemia, all brought about by complexprocessandhasshownitsimportanceastheleading
EBI[2]. determinantofpoorfunctionaloutcomeinpatientssurviving
Accumulating data have suggested that apoptosis is a the initial hemorrhagic insult of SAH. The possible mecha-
key mediator of secondary brain injury after SAH [8]. nismsofEBIandDCIafterSAH,aswellastheirrelationship
Approximately, 50% of SAH survivors remain permanently withCV,areillustratedinFigure1.TheimportanceofCVin
disabledbecauseofcognitivedysfunctionanddonotreturn DCIhaslongbeenoveremphasized.CVisnotthesoleornec-
to their previousfunctions[9]. CV alone could not explain essaryprocessleadingtoDCI.Treatmentstrategiestargeting
the whole subtle changes in behavior and memory. In this at CV prevention alone are not adequate. Considering CV
aspect,apoptosisinducedbyglobalischemiashouldbetaken as the only monitor of therapeutic effectiveness or the lone
intoconsideration. prognosticmarkercanbemisleading.Strategiesfocusingon
Inthisspecialissue,anupdatereviewofthemechanism the detection and treatment of EBI as an alleviation of the
and treatment of CV and DCI after aneurysmal SAH is occurrenceofDCItosubsequentlyimproveoveralloutcome
presented.Therolesofmechanismsincludingmicroclotfor- couldmakepromisingfuturestudyblueprints.
mation,downregulationofendothelialnitricoxidesynthase, Chih-LungLin
and upregulation of relaxin are discussed. Treatment with AaronS.Dumont
progesterone, which attenuates experimental SAH-induced JohnH.Zhang
CV by upregulationofendothelialnitricoxide synthasevia CarlMuroi
Akt signaling pathway, is investigated. Besides, a study on MarioZuccarello
MagnesiumLithospermateB,anactiveextractofsalviamil-
tiorrhizamediatingsGC/cGMP/PKGtranslocationtoreduce
References
CV, is reported. Furthermore, new strategies using 17𝛽-
estradiol, targeting at several CV-preventing mechanisms, [1] D.A.Cook,“Mechanismsofcerebralvasospasminsubarach-
have brought light to the reduction of CV and secondary noidhaemorrhage,”PharmacologyandTherapeutics,vol.66,no.
braininjuryafterSAH.Thetreatmentandoutcomeincluding 2,pp.259–284,1995.
BioMedResearchInternational 3
[2] R.L.Macdonald,“Pathophysiologyandmoleculargeneticsof
vasospasm,”ActaNeurochirurgica,vol.77,supplement,pp.7–11,
2001.
[3] N. W. C. Dorsch, “Cerebral arterial spasm: a clinical review,”
BritishJournalofNeurosurgery,vol.9,no.3,pp.403–412,1995.
[4] E. Tani, “Molecular mechanisms involved in development of
cerebralvasospasm.,”NeurosurgicalFocus,vol.12,no.3,pp.1–4,
2002.
[5] J.B.Bederson,A.L.Levy,W.H.Dingetal.,“Acutevasoconstric-
tionaftersubarachnoidhemorrhage,”Neurosurgery,vol.42,no.
2,pp.352–362,1998.
[6] G. Kusaka, M. Ishikawa, A. Nanda, D. N. Granger, and J.
H. Zhang, “Signaling pathways for early brain injury after
subarachnoidhemorrhage,”JournalofCerebralBloodFlowand
Metabolism,vol.24,no.8,pp.916–925,2004.
[7] F.A.Sehba,R.M.Pluta,andJ.H.Zhang,“Metamorphosisof
subarachnoidhemorrhageresearch:fromdelayedvasospasmto
earlybraininjury,”MolecularNeurobiology,vol.43,no.1,pp.27–
40,2011.
[8] W. J. Cahill, J. H. Calvert, and J. H. Zhang, “Mechanisms of
earlybraininjuryaftersubarachnoidhemorrhage,”Journalof
CerebralBloodFlowandMetabolism,vol.26,no.11,pp.1341–
1353,2006.
[9] K. M. Buchanan, L. J. Elias, and G. B. Goplen, “Differing
perspectivesonoutcomeaftersubarachnoidhemorrhage:the
patient,therelative,theneurosurgeon,”Neurosurgery,vol.46,
no.4,pp.831–840,2000.
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 836397, 9 pages
http://dx.doi.org/10.1155/2014/836397
Research Article
Upregulation of Relaxin after Experimental Subarachnoid
Hemorrhage in Rabbits
YuichiroKikkawa,SatoshiMatsuo,RyotaKurogi,AkiraNakamizo,
MasahiroMizoguchi,andTomioSasaki
DepartmentofNeurosurgery,GraduateSchoolofMedicalSciences,KyushuUniversity,3-1-1Maidashi,
Higashi-ku,Fukuoka,Fukuoka812-8582,Japan
CorrespondenceshouldbeaddressedtoYuichiroKikkawa;[email protected]
Received9March2014;Accepted24June2014;Published16July2014
AcademicEditor:Chih-LungLin
Copyright©2014YuichiroKikkawaetal. This is an open access article distributed under the Creative Commons Attribution
License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly
cited.
Background. Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We
investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH) in rabbits. Methods.
MicroarrayanalysiswithrabbitbasilararteryRNAwasperformed.MessengerRNAexpressionofrelaxin-1andrelaxin/insulin-
likefamilypeptidereceptor1(RXFP1)wasinvestigatedwithquantitativeRT-PCR.RXFP1expressioninthebasilararterywas
investigatedwithimmunohistochemistry.Relaxinconcentrationsincerebrospinalfluid(CSF)andserumwereinvestigatedwith
anenzyme-linkedimmunosorbentassay.Usinghumanbrainvascularsmoothmusclecells(HBVSMC)preincubatedwithrelaxin,
myosinlightchainphosphorylation(MLC)wasinvestigatedwithimmunoblottingafterendothelin-1stimulation.Results.After
SAH,RXFP1mRNAandproteinweresignificantlydownregulatedonday3,whereasrelaxin-1mRNAwassignificantlyupregulated
onday7.TherelaxinconcentrationinCSFwassignificantlyelevatedondays5and7.Pretreatmentwithrelaxinreducedsustained
MLCphosphorylationinducedbyendothelin-1inHBVSMC.Conclusion.UpregulationofrelaxinanddownregulationofRXFP1
afterSAHmayparticipateindevelopmentofcerebralvasospasm.DownregulationofRXFP1mayinduceafunctionaldecreasein
relaxinactivityduringvasospasm.Understandingtheroleofrelaxinmayprovidefurtherinsightintothemechanismsofcerebral
vasospasm.
1.Introduction the mechanism of vasospasm and find new therapeutic
targets.
Cerebralvasospasmisoneofthemostimportantcerebrovas- Relaxin is a small peptide hormone (6kDa) that is
culareventsfollowingsubarachnoidhemorrhage(SAH)and primarily produced by the corpus luteum, decidua, and
is characterized by delayed and prolonged contraction of placentaduringpregnancy[3].Threerelaxingeneshavebeen
cerebral arteries that may cause cerebral ischemia and lead identifiedinhumansandaredesignatedasrelaxin-1(RLN1),
to death or neurological deficits in patients with SAH [1]. relaxin-2 (RLN2), and relaxin-3 (RLN3). Human relaxin-2
Therefore,thepreventionaswellastreatmentofvasospasm is the only form of circulating relaxin that is substantially
isimportantinthemanagementofSAHpatients.Although increased during pregnancy [4]. Human relaxin-2 is func-
increasedproductionofspasmogensandincreasedvascular tionally equivalent to relaxin-1 in all other mammals [5].
responsiveness can be attributed to cerebral vasospasm, Recently, RLN mRNA expression has also been detected
the mechanism of cerebral vasospasm remains elusive, and innonreproductivetissuesincludingarteries,heart,kidney,
thuseffectivetherapeuticstrategiesarenotavailable.Recent liver,andlung[6–8].
randomizedclinicaltrialshaveshownthatcurrentlyavailable Fourrelaxinreceptorgeneshavebeenidentified.Theyare
antivasospasticdrugsarenotsufficienttoimproveoutcome relaxin/insulin-likefamilypeptidereceptorsandarenamed
[2]. Therefore, further research efforts are needed to clarify RXFP1 (RXFP1), RXFP2 (RXFP2), RXFP3 (RXFP3), and