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image of Microthrombosis at the Ultra-early Stages after Experimental Subarachnoid Hemorrhage Results in Early Brain Injury

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 via 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 vs. 25.6 ± 0.63, respectively < 0.0001). CBF was significantly reduced at 12 h post-SAH compared to sham (35.34 ± 8.611 vs. 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
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/content/journals/cnr/10.2174/0115672026362878241220065541
2024-12-26
2025-01-23

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References

  1. Egashira Y. Hua Y. Keep R.F. Xi G. Acute white matter injury after experimental subarachnoid hemorrhage: potential role of lipocalin 2. Stroke 2014 45 7 2141 2143 10.1161/STROKEAHA.114.005307 24893611
    [Google Scholar]
  2. Hu Q. Du Q. Yu W. Dong X. 2-Methoxyestradiol alleviates neuroinflammation and brain edema in early brain injury after subarachnoid hemorrhage in rats. Front. Cell. Neurosci. 2022 16 869546 10.3389/fncel.2022.869546 35558877
    [Google Scholar]
  3. Matsubara H. Imai T. Tsuji S. Oka N. Egashira Y. Enomoto Y. Nakayama N. Nakamura S. Shimazawa M. Iwama T. Hara H. Nafamostat protects against early brain injury after subarachnoid hemorrhage in mice. J. Pharmacol. Sci. 2022 148 1 65 72 10.1016/j.jphs.2021.10.007 34924132
    [Google Scholar]
  4. Egashira Y. Zhao H. Hua Y. Keep R.F. Xi G. White matter injury after subarachnoid hemorrhage: Role of blood-brain barrier disruption and matrix metalloproteinase-9. Stroke 2015 46 10 2909 2915 10.1161/STROKEAHA.115.010351 26374478
    [Google Scholar]
  5. Kilkenny C. Browne W.J. Cuthill I.C. Emerson M. Altman D.G. Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol. 2010 8 6 e1000412 10.1371/journal.pbio.1000412 20613859
    [Google Scholar]
  6. Matsubara H. Imai T. Yamada T. Egashira Y. Nakamura S. Shimazawa M. Iwama T. Hara H. Importance of CBF measurement to exclude concomitant cerebral infarction in the murine endovascular perforation SAH model. J. Stroke Cerebrovasc. Dis. 2020 29 11 105243 10.1016/j.jstrokecerebrovasdis.2020.105243 33066951
    [Google Scholar]
  7. Sugawara T. Ayer R. Jadhav V. Zhang J.H. A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. J. Neurosci. Methods 2008 167 2 327 334 10.1016/j.jneumeth.2007.08.004 17870179
    [Google Scholar]
  8. Imai T. Iwata S. Hirayama T. Nagasawa H. Nakamura S. Shimazawa M. Hara H. Intracellular Fe2+ accumulation in endothelial cells and pericytes induces blood-brain barrier dysfunction in secondary brain injury after brain hemorrhage. Sci. Rep. 2019 9 1 6228 10.1038/s41598‑019‑42370‑z 30996325
    [Google Scholar]
  9. Shi X. Bai H. Wang J. Wang J. Huang L. He M. Zheng X. Duan Z. Chen D. Zhang J. Chen X. Wang J. Behavioral assessment of sensory, motor, emotion, and cognition in rodent models of intracerebral hemorrhage. Front. Neurol. 2021 12 667511 10.3389/fneur.2021.667511 34220676
    [Google Scholar]
  10. Matsubara H. Imai T. Tsuji S. Oka N. Ohba T. Yamada T. Egashira Y. Nakamura S. Shimazawa M. Iwama T. Hara H. Involvement of cerebral blood flow on neurological and behavioral functions after subarachnoid hemorrhage in mice. J. Stroke Cerebrovasc. Dis. 2021 30 9 105952 10.1016/j.jstrokecerebrovasdis.2021.105952 34214963
    [Google Scholar]
  11. Matsumura K. Kumar T.P. Guddanti T. Yan Y. Blackburn S.L. McBride D.W. Neurobehavioral deficits after subarachnoid hemorrhage in mice: Sensitivity analysis and development of a new composite score. J. Am. Heart Assoc. 2019 8 8 e011699 10.1161/JAHA.118.011699 30971151
    [Google Scholar]
  12. Oguzoglu A.S. Senol N. Asci H. Erzurumlu Y. Gulle K. Savran M. Sadef M. Acar B.G. Goksel H.M. Pregabalin protects brain tissue from subarachnoid hemorrhage by enhancing HIF-1alpha/eNOS signaling and VEGF production. World Neurosurg. 2021 152 e713 e720 10.1016/j.wneu.2021.06.011 34129987
    [Google Scholar]
  13. Friedrich B. Müller F. Feiler S. Schöller K. Plesnila N. Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: An in-vivo microscopy study. J. Cereb. Blood Flow Metab. 2012 32 3 447 455 10.1038/jcbfm.2011.154 22146194
    [Google Scholar]
  14. Pang J. Wu Y. Peng J. Yang P. Chen L. Jiang Y. Association of pericyte loss with microthrombosis after subarachnoid hemorrhage in ApoE-deficient mice. Front. Neurol. 2021 12 726520 10.3389/fneur.2021.726520 34566870
    [Google Scholar]
  15. Wang Z. Chen J. Toyota Y. Keep R.F. Xi G. Hua Y. Ultra-early cerebral thrombosis formation after experimental subarachnoid hemorrhage detected on T2* magnetic resonance imaging. Stroke 2021 52 3 1033 1042 10.1161/STROKEAHA.120.032397 33535782
    [Google Scholar]
  16. Ye F. Keep R.F. Hua Y. Garton H.J.L. Xi G. Acute micro-thrombosis after subarachnoid hemorrhage: A new therapeutic target? J. Cereb. Blood Flow Metab. 2021 41 9 2470 2472 10.1177/0271678X211013595 33993796
    [Google Scholar]
  17. Oka F. Hoffmann U. Lee J.H. Shin H.K. Chung D.Y. Yuzawa I. Chen S.P. Atalay Y.B. Nozari A. Hopson K.P. Qin T. Ayata C. Requisite ischemia for spreading depolarization occurrence after subarachnoid hemorrhage in rodents. J. Cereb. Blood Flow Metab. 2017 37 5 1829 1840 10.1177/0271678X16659303 27432225
    [Google Scholar]
  18. Yamada H. Kase Y. Okano Y. Kim D. Goto M. Takahashi S. Okano H. Toda M. Subarachnoid hemorrhage triggers neuroinflammation of the entire cerebral cortex, leading to neuronal cell death. Inflamm. Regen. 2022 42 1 61 10.1186/s41232‑022‑00236‑4 36514181
    [Google Scholar]
  19. Pisapia J.M. Xu X. Kelly J. Yeung J. Carrion G. Tong H. Meghan S. El-Falaky O.M. Grady M.S. Smith D.H. Zaitsev S. Muzykantov V.R. Stiefel M.F. Stein S.C. Microthrombosis after experimental subarachnoid hemorrhage: Time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan. Exp. Neurol. 2012 233 1 357 363 10.1016/j.expneurol.2011.10.029 22079156
    [Google Scholar]
  20. Wu J.S. Lõhelaid H. Shih C.C. Liew H.K. Wang V. Hu W.F. Chen Y.H. Saarma M. Airavaara M. Tseng K.Y. Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke. Mol. Ther. 2024 32 11 4021 4044 10.1016/j.ymthe.2024.09.005 39256999
    [Google Scholar]
  21. Sugawara T. Jadhav V. Ayer R. Chen W. Suzuki H. Zhang J.H. Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats. Stroke 2009 40 4 1530 1532 10.1161/STROKEAHA.108.531699 19228846
    [Google Scholar]
/content/journals/cnr/10.2174/0115672026362878241220065541
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Microthrombosis at the Ultra-early Stages after Experimental Subarachnoid Hemorrhage Results in Early Brain Injury
Bentham Science Publishers ; https://doi.org/10.2174/0115672026362878241220065541
/content/journals/cnr/10.2174/0115672026362878241220065541
/content/journals/cnr/10.2174/0115672026362878241220065541
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  • Article Type:     Research Article
Keywords: thrombin ; matrix metalloproteinase-9 (mmp9) ; cerebral blood flow ; early brain injury ; Swubarachnoid hemorrhage ; neuroinflammation ; microthrombosis

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