Does perfluorocarbon attenuate the severity of SAH by limiting vasospasm and improving tissue oxygenation?
全氟化碳是否可以通过限制血管痉挛和改善组织氧合来减轻 SAH 的严重程度?
基本信息
- 批准号:10604708
- 负责人:
- 金额:$ 22.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-15 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAcuteAffectAftercareAirAir EmbolismAnatomyAreaAttenuatedBloodBlood VesselsBlood capillariesBlood flowBrainBrain InjuriesBrain PathologyBrain hemorrhageBrain regionCaliberCerebral IschemiaCerebrovascular CirculationCerebrovascular SpasmCerebrumClinicalCoagulation ProcessComplexCritical CareDataDevelopmentDiffuseDoseDrug KineticsDrug usageEarly InterventionElementsEmulsionsEndotheliumErythrocytesFemaleFluorocarbonsFunctional disorderFutureGasesGoalsHalf-LifeHemoglobinHourHumanHuman ResourcesHyperbaric OxygenImpairmentIschemic StrokeLeadLipidsLiquid substanceMethodsMitochondriaModelingMolecularMonitorMusNutrientOutcomeOxidative StressOxygenOxygentPartial PressureParticle SizePathologicPathologyPatient CarePatientsPercussionPerforationPharmacodynamicsPlasmaPlayReportingResearchResearch PersonnelResidual stateResolutionRiskRodent ModelRoleSafetySeveritiesSolubilityStriated MusclesSubarachnoid HemorrhageSupportive careTestingTherapeuticTherapeutic InterventionTimeTissue SampleTissuesTrainingTranslatingVasospasmarteriolebasecare providerscell motilitycerebral oxygenationdrug candidatedrug repurposingefficacy testingflexibilityfunctional outcomeshuman dataimprovedmalemitochondrial dysfunctionmortalityneuropathologynoveloptimal treatmentsparticlepre-clinicalpreclinical trialpressurepreventprimary outcometherapeutically effectivetissue oxygenationtreatment strategy
项目摘要
Subarachnoid hemorrhage (SAH) is one of the deadliest of hemorrhagic stroke types; however, no effective
therapeutic intervention is yet available, other than supportive care. Vasospasm is reported to trigger within the
first three days after the onset of SAH and sustain for 1-2 weeks. The vasospasm results in delayed cerebral
ischemia (DCI) which is considered as the main cause of mortality after SAH. Since vasospasm leads to a
decrease in O2 level in the affected regions of the brain, novel methods to supply O2 to the compromised brain
region could play a critical role in salvaging the area at risk.
Hyperbaric oxygen/air therapy may have a beneficial effect in decreasing the pathophysiology of SAH by
increasing dissolved tissue O2. However, such treatment is complex, time-limited (a few hours at a time),
extensive monitoring, and trained personnel. Therefore, here we propose perfluorocarbon (PFC)-based
emulsion Oxygent (referred to as PFC-Oxygent onwards), which increases dissolved O2 in blood and tissue.
PFC-Oxygent is reported to have an extended half-life of about 3d. PFCs are emulsified compounds that can
carry and release O2 fundamentally differently than does the hemoglobin. The particle size of these emulsions
allows for PFCs to get to places where red blood cells are blocked such as capillaries affected in SAH.
In a model of striated muscle and cerebral air embolism, we have shown that PFC-Oxygent increased cerebral
blood flow and delivered O2 to the affected area even with little or no red cell movement. Moreover, in preclinical
TBI, we showed that PFC-Oxygent augments cerebral O2 level. These data indicate the therapeutic potential of
PFC-Oxygent in an acute cerebral pathology and its potential efficacy in SAH where cerebral vasospasm plays
a vital role in the progression of pathological and functional outcomes. Since PFC is well tolerated in humans
and the safety profile of this compound has already been tested, it is a prime candidate for drug repurposing.
Here, we are testing the hypothesis that PFC-Oxygent treatment after SAH can increase O2 delivery to the
compromised area after the SAH, attenuate oxidative stress, and improve pathological/functional outcomes.
Aim 1: To test whether PFC rescues functional outcomes and neuropathology after SAH. This aim will test the
effect of PFC-Oxygent on functional and anatomical outcomes after SAH in young and old male and female
mice.
Aim 2: To test whether PFC improves tissue oxygenation and cerebral blood flow following SAH. In this aim, we
will test whether PFC improves local/global cerebral oxygenation, tissue sampled mitochondrial activity, and
reduces oxidative stress after SAH.
The proposed study will collectively provide the robustness of the therapeutic potential of this clinically used drug
in SAH. Because most of the pharmacokinetics, pharmacodynamics, and safety of PFC-Oxygent is known,
repurposing of this drug in regulating SAH outcomes would be expedited and of high translational value.
蛛网膜下腔出血(SAH)是最致命的出血性中风类型之一;然而,没有效果
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Abdullah S Ahmad其他文献
Abdullah S Ahmad的其他文献
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{{ truncateString('Abdullah S Ahmad', 18)}}的其他基金
Does perfluorocarbon attenuate the severity of SAH by limiting vasospasm and improving tissue oxygenation?
全氟化碳是否可以通过限制血管痉挛和改善组织氧合来减轻 SAH 的严重程度?
- 批准号:
10288921 - 财政年份:2021
- 资助金额:
$ 22.8万 - 项目类别:
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