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AuthorPir, Ghulam Jeelani
AuthorParray, Aijaz
AuthorAyadathil, Raheem
AuthorPananchikkal, Sajitha V.
AuthorMir, Fayaz Ahmad
AuthorMuhammad, Islam
AuthorAbubakar, Ahmed
AuthorAmir, Nueman
AuthorHussain, Sohail
AuthorHaroon, Khawaja H.
AuthorMuhammad, Ahmad
AuthorImam, Yahya
AuthorPatro, Satya Narayana
AuthorAkhtar, Naveed
AuthorZakaria, Aymen
AuthorKamran, Saadat
Available date2023-07-06T11:22:49Z
Publication Date2022-11-21
Publication NameInternational Journal of Molecular Sciences
Identifierhttp://dx.doi.org/10.3390/ijms232214477
CitationPir, G. J., Parray, A., Ayadathil, R., Pananchikkal, S. V., Mir, F. A., Muhammad, I., ... & Kamran, S. (2022). Platelet–Neutrophil Association in NETs-Rich Areas in the Retrieved AIS Patient Thrombi. International Journal of Molecular Sciences, 23(22), 14477.
ISSN1661-6596
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85142806490&origin=inward
URIhttp://hdl.handle.net/10576/45128
AbstractHistological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase+ and neutrophil-elastase+) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.
SponsorThis research was funded by a grant awarded by Medical Research Council (MRC), Hamad Medical Corporation (HMC) (grant number IRGC-02-SI-029).
Languageen
PublisherMultidisciplinary Digital Publishing Institute (MDPI)
SubjectAIS
fibrin
HMGB1
leukocytes
NETs
neutrophils
platelets
stroke
t-PA
von Willebrand factor
TitlePlatelet–Neutrophil Association in NETs-Rich Areas in the Retrieved AIS Patient Thrombi
TypeArticle
Issue Number22
Volume Number23
ESSN1422-0067
dc.accessType Open Access


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