Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Neurovascular Research
  4. Volume 21, Issue 5
  5. Article
Volume 21, Issue 5
  • ISSN: 1567-2026
  • E-ISSN: 1875-5739

Abstract

Introduction

Early Brain Injury (EBI) significantly contributes to poor neurological outcomes and death following subarachnoid hemorrhage (SAH). The mechanisms underlying EBI post-SAH remain unclear. This study explores the relationship between serial cerebral blood flow (CBF) changes and neurological symptoms, as well as the mechanisms driving CBF changes in the ultra-early stages after experimental SAH in mice.

Methods

SAH was induced by endovascular perforation in male ddY mice. Mice were sacrificed at 6, 12, 24, and 48 h after behavioral tests using the modified neurological score and grid walking test, and CBF was measured Laser Speckle Flow Imaging (LSFI). Neurofunctional evaluation, CBF analysis, and Western blotting were used to assess SAH-induced damage.

Results

Neurological symptoms were significantly worse at 12 h post-SAH compared to sham (9.5 ± 1.7 . 25.6 ± 0.63, respectively; < 0.0001). CBF was significantly reduced at 12 h post-SAH compared to sham (35.34 ± 8.611 . 91.06 ± 12.45, respectively; < 0.0001). Western blotting revealed significantly elevated thrombin and matrix metalloproteinase 9 levels 12 h post-SAH ( < 0.05).

Conclusion

Our results suggest that microthrombus formation peaked at 12 h post-SAH, potentially causing EBI and worsening neurological symptoms. Microthrombus formation in the ultra-early stages may represent a novel therapeutic target for managing EBI.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cnr/10.2174/0115672026362878241220065541
2024-12-26
2025-04-13

  • From This Site

    /content/journals/cnr/10.2174/0115672026362878241220065541
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. EgashiraY. HuaY. KeepR.F. XiG. Acute white matter injury after experimental subarachnoid hemorrhage: Potential role of lipocalin 2.Stroke20144572141214310.1161/STROKEAHA.114.00530724893611
     [Google Scholar]
  2. HuQ. DuQ. YuW. DongX. 2-Methoxyestradiol alleviates neuroinflammation and brain edema in early brain injury after subarachnoid hemorrhage in rats.Front. Cell. Neurosci.20221686954610.3389/fncel.2022.86954635558877
     [Google Scholar]
  3. MatsubaraH. ImaiT. TsujiS. OkaN. EgashiraY. EnomotoY. NakayamaN. NakamuraS. ShimazawaM. IwamaT. HaraH. Nafamostat protects against early brain injury after subarachnoid hemorrhage in mice.J. Pharmacol. Sci.20221481657210.1016/j.jphs.2021.10.00734924132
     [Google Scholar]
  4. EgashiraY. ZhaoH. HuaY. KeepR.F. XiG. White matter injury after subarachnoid hemorrhage: Role of blood-brain barrier disruption and matrix metalloproteinase-9.Stroke201546102909291510.1161/STROKEAHA.115.01035126374478
     [Google Scholar]
  5. KilkennyC. BrowneW.J. CuthillI.C. EmersonM. AltmanD.G. Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research.PLoS Biol.201086e100041210.1371/journal.pbio.100041220613859
     [Google Scholar]
  6. MatsubaraH. ImaiT. YamadaT. EgashiraY. NakamuraS. ShimazawaM. IwamaT. HaraH. Importance of CBF measurement to exclude concomitant cerebral infarction in the murine endovascular perforation SAH model.J. Stroke Cerebrovasc. Dis.2020291110524310.1016/j.jstrokecerebrovasdis.2020.10524333066951
     [Google Scholar]
  7. SugawaraT. AyerR. JadhavV. ZhangJ.H. A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model.J. Neurosci. Methods2008167232733410.1016/j.jneumeth.2007.08.00417870179
     [Google Scholar]
  8. ImaiT. IwataS. HirayamaT. NagasawaH. NakamuraS. ShimazawaM. HaraH. Intracellular Fe2+ accumulation in endothelial cells and pericytes induces blood-brain barrier dysfunction in secondary brain injury after brain hemorrhage.Sci. Rep.201991622810.1038/s41598‑019‑42370‑z30996325
     [Google Scholar]
  9. ShiX. BaiH. WangJ. WangJ. HuangL. HeM. ZhengX. DuanZ. ChenD. ZhangJ. ChenX. WangJ. Behavioral assessment of sensory, motor, emotion, and cognition in rodent models of intracerebral hemorrhage.Front. Neurol.20211266751110.3389/fneur.2021.66751134220676
     [Google Scholar]
  10. MatsubaraH. ImaiT. TsujiS. OkaN. OhbaT. YamadaT. EgashiraY. NakamuraS. ShimazawaM. IwamaT. HaraH. Involvement of cerebral blood flow on neurological and behavioral functions after subarachnoid hemorrhage in mice.J. Stroke Cerebrovasc. Dis.202130910595210.1016/j.jstrokecerebrovasdis.2021.10595234214963
     [Google Scholar]
  11. MatsumuraK. KumarT.P. GuddantiT. YanY. BlackburnS.L. McBrideD.W. Neurobehavioral deficits after subarachnoid hemorrhage in mice: Sensitivity analysis and development of a new composite score.J. Am. Heart Assoc.201988e01169910.1161/JAHA.118.01169930971151
     [Google Scholar]
  12. OguzogluA.S. SenolN. AsciH. ErzurumluY. GulleK. SavranM. SadefM. AcarB.G. GokselH.M. Pregabalin protects brain tissue from subarachnoid hemorrhage by enhancing HIF-1alpha/eNOS signaling and VEGF production.World Neurosurg.2021152e713e72010.1016/j.wneu.2021.06.01134129987
     [Google Scholar]
  13. FriedrichB. MüllerF. FeilerS. SchöllerK. PlesnilaN. Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: An in-vivo microscopy study.J. Cereb. Blood Flow Metab.201232344745510.1038/jcbfm.2011.15422146194
     [Google Scholar]
  14. PangJ. WuY. PengJ. YangP. ChenL. JiangY. Association of pericyte loss with microthrombosis after subarachnoid hemorrhage in ApoE-deficient mice.Front. Neurol.20211272652010.3389/fneur.2021.72652034566870
     [Google Scholar]
  15. WangZ. ChenJ. ToyotaY. KeepR.F. XiG. HuaY. Ultra-early cerebral thrombosis formation after experimental subarachnoid hemorrhage detected on T2* magnetic resonance imaging.Stroke20215231033104210.1161/STROKEAHA.120.03239733535782
     [Google Scholar]
  16. YeF. KeepR.F. HuaY. GartonH.J.L. XiG. Acute micro-thrombosis after subarachnoid hemorrhage: A new therapeutic target?J. Cereb. Blood Flow Metab.20214192470247210.1177/0271678X21101359533993796
     [Google Scholar]
  17. OkaF. HoffmannU. LeeJ.H. ShinH.K. ChungD.Y. YuzawaI. ChenS.P. AtalayY.B. NozariA. HopsonK.P. QinT. AyataC. Requisite ischemia for spreading depolarization occurrence after subarachnoid hemorrhage in rodents.J. Cereb. Blood Flow Metab.20173751829184010.1177/0271678X1665930327432225
     [Google Scholar]
  18. YamadaH. KaseY. OkanoY. KimD. GotoM. TakahashiS. OkanoH. TodaM. Subarachnoid hemorrhage triggers neuroinflammation of the entire cerebral cortex, leading to neuronal cell death.Inflamm. Regen.20224216110.1186/s41232‑022‑00236‑436514181
     [Google Scholar]
  19. PisapiaJ.M. XuX. KellyJ. YeungJ. CarrionG. TongH. MeghanS. El-FalakyO.M. GradyM.S. SmithD.H. ZaitsevS. MuzykantovV.R. StiefelM.F. SteinS.C. Microthrombosis after experimental subarachnoid hemorrhage: Time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan.Exp. Neurol.2012233135736310.1016/j.expneurol.2011.10.02922079156
     [Google Scholar]
  20. WuJ.S. LõhelaidH. ShihC.C. LiewH.K. WangV. HuW.F. ChenY.H. SaarmaM. AiravaaraM. TsengK.Y. Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.Mol. Ther.202432114021404410.1016/j.ymthe.2024.09.00539256999
     [Google Scholar]
  21. SugawaraT. JadhavV. AyerR. ChenW. SuzukiH. ZhangJ.H. Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats.Stroke20094041530153210.1161/STROKEAHA.108.53169919228846
     [Google Scholar]
/content/journals/cnr/10.2174/0115672026362878241220065541
Loading
Microthrombosis at the Ultra-early Stages after Experimental Subarachnoid Hemorrhage Results in Early Brain Injury
Curr Neurovasc Res 21, 529 (2024); https://doi.org/10.2174/0115672026362878241220065541
/content/journals/cnr/10.2174/0115672026362878241220065541
/content/journals/cnr/10.2174/0115672026362878241220065541
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): cerebral blood flow; early brain injury; matrix metalloproteinase-9; microthrombosis; neuroinflammation; Subarachnoid hemorrhage; thrombin

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test