The Formation of Microthrombi in Parenchymal Microvessels after Traumatic Brain Injury Is Independent of Coagulation Factor XI

Journal of Neurotrauma
Susanne M SchwarzmaierNikolaus Plesnila

Abstract

Microthrombus formation and bleeding worsen the outcome after traumatic brain injury (TBI). The aim of the current study was to characterize these processes in the brain parenchyma after experimental TBI and to determine the involvement of coagulation factor XI (FXI). C57BL/6 mice (n = 101) and FXI-deficient mice (n = 15) were subjected to controlled cortical impact (CCI). Wild-type mice received an inhibitory antibody against FXI (14E11) or control immunoglobulin G 24 h before or 30 or 120 min after CCI. Cerebral microcirculation was visualized in vivo by 2-photon microscopy 2-3 h post-trauma and histopathological outcome was assessed after 24 h. TBI induced hemorrhage and microthrombus formation in the brain parenchyma (p < 0.001). Inhibition of FXI activation or FXI deficiency did not reduce cerebral thrombogenesis, lesion volume, or hemispheric swelling. However, it also did not increase intracranial hemorrhage. Formation of microthrombosis in the brain parenchyma after TBI is independent of the intrinsic coagulation cascade since it was not reduced by inhibition of FXI. However, since targeting FXI has well-established antithrombotic effects in humans and experimental animals, inhibition of FXI could represent a reasonable...Continue Reading

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Citations

Nov 11, 2017·Journal of Neurotrauma·Yanlu ZhangYe Xiong
Apr 7, 2020·Expert Opinion on Therapeutic Targets·Jason K KarimyKristopher T Kahle
Nov 28, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Xiaotang MaJames Haorah
Jun 16, 2017·Neural Regeneration Research·Ilknur KeskinErtugrul Kilic
Aug 2, 2017·Acta Neuropathologica·Gemma LloveraArthur Liesz
May 17, 2021·Experimental Neurology·Zachary M WeilA Courtney DeVries
Dec 28, 2021·Pediatric Blood & Cancer·Assaf Arie BargGili Kenet

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Methods Mentioned

BETA
antisense oligonucleotides

Software Mentioned

Leica
Imaris
Sigma Stat
ImageJ

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