S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Abstract

Background and purposePost-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.MethodsWe analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.ResultsPTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.ConclusionsHigher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation.

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology

“…However, further work correlating BNP and NT-proBNP expression with longer-term patient outcome measures is needed. Nonetheless, as previously observed for other possible stroke biomarkers [ 48 ], our observation of the presence and localization of BNP and NT-proBNP in clots indicates that they might be involved in thrombosis, uncovering novel features of the thrombo-inflammatory pathway leading to pathological thrombus formation, which is certainly worth of further study.…”

Diffusion MRI Fiber Tractography and Benzodiazepine SPECT Imaging for Assessing Neural Damage to the Language Centers in an Elderly Patient after Successful Reperfusion Therapy

“…During the acute/subacute stroke phase, spreading depolarization has been increasingly recognized as a key pathologic event that occurs spontaneously and contributes to secondary brain injury [ 32 ]. Measuring the content of potential biomarkers (e.g., S100b and neuron-specific enolase) that reflect neuronal damage and blood–brain barrier disruption could be useful for early clinical evaluations and outcomes after thrombolytic therapy [ 33 , 34 ]. However, specific and effective approaches that visualize the suppression of neuronal activity are not yet available.…”

The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker

“…S100B levels in biological fluids constitute a recognized clinical parameter to evaluate patients with acute brain injury [52][53][54][55][56][57][58][59][60], and a special emphasis has been recently placed on mild traumatic brain injury [61][62][63][64][65][66][67][68][69][70][71] since S100B levels have been proposed as a reliable screening tool in this pathological condition. S100B levels in human brain tissue and their direct correlation with S100B in biological fluids are difficult to evaluate.…”