Red Blood Cell Microparticles Limit Hemorrhage Following Intracerebral Hemorrhage in Spontaneously Hypertensive Rats

HomeStrokeVol. 54, No. 4Red Blood Cell Microparticles Limit Hemorrhage Following Intracerebral Hemorrhage in Spontaneously Hypertensive Rats Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUBRed Blood Cell Microparticles Limit Hemorrhage Following Intracerebral Hemorrhage in Spontaneously Hypertensive Rats Ashish K. Rehni, Sunjoo Cho, Hever Navarro Quero, Zhexuan Zhang, Chuanhui Dong, Weizhao Zhao, Miguel A. Perez-Pinzon, Sebastian Koch, Wenche Jy and Kunjan R. Dave Ashish K. RehniAshish K. Rehni https://orcid.org/0000-0002-9107-3277 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories (A.K.R., S.C., M.A.P.-P., K.R.D.), University of Miami, Coral Gables, FL. Department of Neurology (A.K.R., S.C., C.D., M.A.P.-P., S.K., K.R.D.), University of Miami, Coral Gables, FL. *A.K. Rehni and S. Cho contributed equally. Search for more papers by this author , Sunjoo ChoSunjoo Cho Peritz Scheinberg Cerebral Vascular Disease Research Laboratories (A.K.R., S.C., M.A.P.-P., K.R.D.), University of Miami, Coral Gables, FL. Department of Neurology (A.K.R., S.C., C.D., M.A.P.-P., S.K., K.R.D.), University of Miami, Coral Gables, FL. *A.K. Rehni and S. Cho contributed equally. Search for more papers by this author , Hever Navarro QueroHever Navarro Quero Department of Medicine, University of Miami Miller School of Medicine (H.N.Q., W.J.), University of Miami, Coral Gables, FL. Search for more papers by this author , Zhexuan ZhangZhexuan Zhang https://orcid.org/0000-0002-8149-9186 Department of Biomedical Engineering (Z.Z., W.Z.), University of Miami, Coral Gables, FL. Search for more papers by this author , Chuanhui DongChuanhui Dong Department of Neurology (A.K.R., S.C., C.D., M.A.P.-P., S.K., K.R.D.), University of Miami, Coral Gables, FL. Search for more papers by this author , Weizhao ZhaoWeizhao Zhao https://orcid.org/0000-0002-9890-5785 Department of Biomedical Engineering (Z.Z., W.Z.), University of Miami, Coral Gables, FL. Search for more papers by this author , Miguel A. Perez-PinzonMiguel A. Perez-Pinzon https://orcid.org/0000-0001-6555-8935 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories (A.K.R., S.C., M.A.P.-P., K.R.D.), University of Miami, Coral Gables, FL. Department of Neurology (A.K.R., S.C., C.D., M.A.P.-P., S.K., K.R.D.), University of Miami, Coral Gables, FL. Neuroscience Program (M.A.P.-P., K.R.D.), University of Miami, Coral Gables, FL. Search for more papers by this author , Sebastian KochSebastian Koch https://orcid.org/0000-0003-0244-6033 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories (A.K.R., S.C., M.A.P.-P., K.R.D.), University of Miami, Coral Gables, FL. Search for more papers by this author , Wenche JyWenche Jy Department of Medicine, University of Miami Miller School of Medicine (H.N.Q., W.J.), University of Miami, Coral Gables, FL. Search for more papers by this author and Kunjan R. DaveKunjan R. Dave Correspondence to: Kunjan R. Dave, PhD, Department of Neurology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, RMSB No. 7046, Miami, FL 33136. Email E-mail Address: [email protected] https://orcid.org/0000-0002-0173-5338 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories (A.K.R., S.C., M.A.P.-P., K.R.D.), University of Miami, Coral Gables, FL. Department of Neurology (A.K.R., S.C., C.D., M.A.P.-P., S.K., K.R.D.), University of Miami, Coral Gables, FL. Neuroscience Program (M.A.P.-P., K.R.D.), University of Miami, Coral Gables, FL. Search for more papers by this author Originally published2 Mar 2023https://doi.org/10.1161/STROKEAHA.122.042152Stroke. 2023;54:e152–e154Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 2, 2023: Ahead of Print Hematoma expands over time in spontaneous intracerebral hemorrhage (sICH) and correlates with post-sICH neurological impairment.1 Hypertension is a major risk factor for sICH, resulting in increased hematoma volume, worse outcomes, and increased mortality following sICH.2 We previously demonstrated that red blood cell–derived microparticles (RMPs) enhance both primary and secondary hemostasis and limit hematoma expansion in naive rats following collagenase-induced sICH.3,4 Considering the importance of validating the efficacy of new drugs in animals suffering from risk factors or comorbidities to improve the translational value of preclinical studies, we evaluated RMP efficacy in limiting hematoma growth and related neurological deficits following sICH in male SHR (spontaneously hypertensive) rats, compared with their respective control, male WKY (Wistar-Kyoto) rats. Experimental details are provided in the Supplemental Material.Animal experiments were performed as per the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the University of Miami Institutional Animal Care and Use Committee. Physiological parameters (Table S1) and blood pressure (Figure S1) were all within normal ranges. The hematoma volume in RMP-treated WKY rats was significantly lower (87±9 mm3; n=10; P<0.001) than in vehicle-treated WKY rats (141±10; n=10; Figure [B]). The hematoma volume in RMP-treated SHR rats was also significantly lower (85±9 mm3; n=10; P<0.01) than in vehicle-treated SHR rats (130±10; n=10; Figure [B]). The hematoma frequency maps showed that the hematoma volumes in RMP-treated WKY and SHR rat groups were smaller at multiple coronal levels when compared with their respective vehicle group (Figure [D]). The neurological scores in RMP-treated WKY and SHR rats were significantly lower than in their respective vehicle-treated rats (Figure [C]). These results demonstrate that RMPs can limit hematoma growth and lower neurological deficits following post-collagenase injection in SHR rats.Download figureDownload PowerPointFigure. The effect of red blood cell-derived microparticle (RMP) treatment on hematoma expansion postcollagenase-induced intracerebral hemorrhage in spontaneously hypertensive (SHR) rats. Experimental design (A); hematoma volume (B); neurological score determined 24 hours post-spontaneous intracerebral hemorrhage (C); and hematoma frequency maps at 7 coronal levels (D). BP indicates blood pressure; and WKY, Wistar-Kyoto. ⁂P<0.001 vs vehicle-treated WKY rats. ††P<0.01 vs vehicle-treated SHR rats.No significant difference in the hematoma volume was observed between vehicle-treated SHR rats and normotensive vehicle-treated WKY rats and between RMP-treated SHR rats and WKY rats (Supplemental Results). These results are in line with a previous study that did not find differences in hematoma size between WKY and SHR rats.5 We previously observed that RMPs exert a substantial ameliorative effect on hematoma growth and neurological impairment in naive rats 24 hours after sICH induction and RMP treatment resulted in significantly improved long-term behavioral and histological outcomes.4 Independent replication and evaluating the effects in female and aged animals and in a different species remain to be addressed. We conclude that RMP treatment is able to limit hematoma growth and attenuate neurological impairment post-sICH in an animal model of hypertension—a prominent risk factor for sICH.Data AvailabilityAll data generated or analyzed during this study are included in this article and the Supplemental Material.Article InformationAcknowledgmentsWe thank Dr Brant Watson for critical reading of this article.Sources of FundingThis work was supported by the National Institutes of Health (NS094896) and the James and Esther King Biomedical Research Program (9JK08). The funding agencies were not involved in the collection, analysis, and interpretation of data; in writing of the report; or in the decision to submit the manuscript for publication.Supplemental MaterialSupplemental Materials and MethodsSupplemental ResultsTable S1Figure S1Nonstandard Abbreviations and AcronymsRMPred blood cell–derived microparticleSHRspontaneously hypertensivesICHspontaneous intracerebral hemorrhageWKYWistar-KyotoDisclosures RxMP Therapeutics provided the testing material. Dr Jy and the University of Miami have partial ownership in RxMP Therapeutics. Dr Jy received grant support for nonrelated work from RxMP Therapeutics and is the inventor of US patents related to red cell microparticles and serves as a scientific advisor/consultant to RxMP Therapeutics.Footnotes*A.K. Rehni and S. Cho contributed equally.This manuscript was sent to Jean-Claude Baron, Guest Editor, for review by expert referees, editorial decision, and final disposition.For Sources of Funding and Disclosures, see page e154.Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.122.042152.Correspondence to: Kunjan R. Dave, PhD, Department of Neurology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, RMSB No. 7046, Miami, FL 33136. Email kdave@med.miami.eduReferences1. Lord AS, Gilmore E, Choi HA, Mayer SA; VISTA-ICH Collaboration. Time course and predictors of neurological deterioration after intracerebral hemorrhage.Stroke. 2015; 46:647–65210.1161/STROKEAHA.114.007704LinkGoogle Scholar2. Francoeur CL, Mayer SA; VISTA-ICH Collaborators. Acute blood pressure and outcome after intracerebral hemorrhage: the VISTA-ICH cohort.J Stroke Cerebrovasc Dis. 2021; 30:105456. 10.1016/j.jstrokecerebrovasdis.2020.105456CrossrefGoogle Scholar3. Jy W, Johansen ME, Bidot C, Horstman LL, Ahn YS. Red cell-derived microparticles (rmp) as haemostatic agent.Thromb Haemost. 2013; 110:751–760. doi: 10.1160/TH12-12-0941CrossrefGoogle Scholar4. Rehni AK, Cho S, Quero HN, Shukla V, Zhang Z, Dong C, Zhao W, Perez-Pinzon MA, Koch S, Jy W, et al. Red blood cell microparticles limit hematoma growth in intracerebral hemorrhage.Stroke. 2022; 53:3182–3191. doi: 10.1161/STROKEAHA.122.039641LinkGoogle Scholar5. Wu G, Bao X, Xi G, Keep RF, Thompson BG, Hua Y. Brain injury after intracerebral hemorrhage in spontaneously hypertensive rats.J Neurosurg. 2011; 114:1805–1811. doi: 10.3171/2011.1.JNS101530CrossrefGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails April 2023Vol 54, Issue 4 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.122.042152PMID: 36861474 Originally publishedMarch 2, 2023 Keywordsrats, inbred SHRcell-derived microparticlesratsrats, inbred WKYcerebral hemorrhagePDF download Advertisement SubjectsIntracranial Hemorrhage