Inflammatory biomarkers in blood of patients with acute brain ischemia

Abstract

Although many failed surrogate markers are provided in the literature, inflammation may contribute to the outcome of ischemic stroke. In 50 consecutive patients with acute ischemic stroke, in the absence of symptoms and signs of concomitant infection, we evaluated a panel of biomarkers reported to be variably associated with brain ischemia, and correlate their serum level with the brain lesion volume and clinical outcome. Infarct size was calculated on computed tomography (CT) scans by means of the Cavalieri's method. Neurological impairment was scored by using the Glasgow Coma Scale, Glasgow Outcome Scale and National Institutes of Health (NIH) scales at stroke onset and 3-month follow-up. Some markers showed a direct significant correlation with both initial and final NIH scale and with infarct size, particularly tumor necrosis factor alpha (TNF-alpha) (P=0.002), intercellular adhesion molecule-1 (P<0.01) and matrix metalloproteinase-2/9 (P=0.001). In contrast to previous reports, interleukin-6 (IL-6) serum level showed a significant inverse correlation with both final neurological impairment and infarct size (P<0.001). This novel finding allows us suggesting that IL-6, in the context of a complex pro-inflammatory network occurring during stroke, is associated with neuroprotection rather than neurotoxicity in patients with ischemic brain injury.

Blood Biomarkers of Ischemic Stroke

“…A larger infarct volume might also lead to a greater inflammatory response to the ischemic tissue. This is supported by studies showing elevated inflammatory markers are associated with infarct volume, including TNF-α [53], IL-6 [54,55], ICAM-1 [53], MMP-2 and MMP-9 [53,56].…”

“…Myelination of CNS>PNS Diagnosis [104] Infarct volume [103] Stroke severity [103] Inflammatory Biomarkers CRP Liver synthesis Acute phase reactant, role in atherotherombosis & ischemic injury [105] Diagnosis [106] Stroke risk [62,[107][108][109] IL-6 Cytokine from T-cells+ macrophages Acute phase response, fever Infarct volume [53][54][55]110] Stroke Severity [110] END [53,54] TNF-α Cytokine, inflammatory cells Inflammation, Acute phase response Infarct volume [53] Stroke Severity [53] END [72] VCAM 1 Immunoglobulin Leukocyte-endothelial cell interaction Diagnosis [19] Infarct volume [53] ICAM 1 Immunoglobulin Leukocyte-endothelial cell interaction…”

“…Infarct volume [53] Stroke severity [53] END [72] MMP2, MMP9 Gelatinase Proteolytic enzymes Degrades collage causing endothelial damage, plaque matrix disruption Diagnosis [19,20] Infarct volume [53] Stroke severity [53] Hemorrhagic transformation [77][78][79][80] Growth factor Growth and differentiation of neurons Diagnosis [20] bent assay (ELISA), 2D gel electrophoresis, and mass spectrometry (matrix assisted laser desorption/ionization analysis). Using these techniques a number of proteins and panels of proteins have been identified as biomarkers of ischemic stroke (Table 1).…”

Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction

“…Cranial computerized tomography (CT) findings as major early signs also show that ischemia covering is more than 30% at occlusion site (Sparacia, Iaia, Assadi, & Lagalla, 2007). Recently, accumulated evidences have stressed the important roles of inflammatory reaction mediated by cytokines in the pathophysiology of acute brain ischemia (Sotgiu et al, 2006;Vila, Castillo, Dávalos, & Chamorro, 2000). The plasma levels of some inflammatory cytokines, such as tumor necrosis factor (TNF-α) and interleukin (IL)-6, are reported to be a predictive diagnosis of acute ischemic stroke in the acute setting (Tuttolomondo, Di Raimondo, di Sciacca, Pinto, & Licata, 2008).…”

Microglia and Chitotriosidase in Multiple Sclerosis

“…37 Besides the increase of innate immune cytokines, we and others 38,39 have also found increased Chit activity in stroke, suggesting a relevant role for infiltrated macrophages, or resident microglia activated by the ischaemic event, inside the brain. Our results also suggest that Chit, TNF-α and other pro-inflammatory cytokines are markers of microglia activation occurring during a stroke, which is independent of pre-existing inflammatory or infectious conditions of the patients.…”