ABSTRACT
Stroke is a major public health problem that can cause a long-term disability or death due to brain damage. Serious stroke is frequently caused by a large vessel occlusion in the anterior circulation, which should be treated by endovascular embolectomy if possible. In this study, we investigated the use of the brain damage biomarkers tau, NFL, NSE, GFAp, and S100B to understand the progression of nervous tissue damage and their relationship to outcome in such stroke after endovascular treatment. Blood samples were taken from 90 patients pre-treatment and 2 h, 24 h, 48 h, 72 h and 3 months after endovascular treatment. Stroke-related neurological deficit was estimated using the National Institute of Health Stroke Scale (NIHSS) at admission and at 24 h. Neurological outcome was evaluated at 3 months. After stroke, tau, NFL, GFAp and S100B increased in a time dependent manner, while NSE remained constant over time. At 3 months, tau and GFAp levels were back to normal whereas NFL was still high. Tau, NFL and GFAp correlated well to outcome, as well as to infarct volume and NIHSS at 24 h. The best time for prediction of poor outcome was different for each biomarker. However, the combination of NIHSS at 24 h with either tau, NFL or GFAp at 48 h gave the best prediction. The use of biomarkers in the early setting after endovascular treatment of stroke will lead to a simplified and standardized way to estimate the nervous tissue damage and possibly complement the clinical judgement in foreseeing the need of rehabilitation measures.
Subject(s)
Brain Injuries , Endovascular Procedures , Stroke , Biomarkers , Embolectomy , Humans , Stroke/diagnostic imaging , Stroke/surgery , Treatment OutcomeABSTRACT
BACKGROUND: Neurofilament light (NFL) is a well-validated biomarker for neuronal injury and neurodegeneration. Increased cerebrospinal fluid (CSF) levels have been shown after stroke, as well as in patients with a broad range of neurodegenerative and neuroinflammatory diseases. Neurofilament heavy (NFH) belongs to the same family of structural proteins but it is less extensively studied. The potential of phosphorylated NFH (pNFH) as a stroke biomarker and for the prediction of clinical outcome is unknown. In this study, we aimed to examine the temporal pattern of NFL and pNFH concentrations in serum and CSF after acute ischemic stroke. MATERIALS AND METHODS: A quantitative Enzyme-Linked ImmunoSorbent Assay (ELISA) for pNFH was developed and tested on CSF and serum samples. NFL and pNFH were analysed in serum and CSF of acute ischemic stroke patients, who were followed over time (Day 0-1, Day 2-3, Day 7-9, three weeks, and 3-5 months after stroke). RESULTS: NFL and pNFH concentrations in serum and CSF increased after stroke, peaked during the 3rd week, and then decreased back to almost baseline levels at 3-5 months. CSF-NFL and serum-NFL correlated to the outcome measured by Barthel Index after 3-5 months, whilst no such association was seen for pNFH. DISCUSSION: These findings suggest that NFL and pNFH in both CSF and serum reflect the temporal pattern of the post ischemic axonal injury and that this process does not seem to progress after 3-5 months. CONCLUSION: NFL and pNFH in CSF and serum are promising biomarkers for axonal injury following stroke. Further studies in larger populations are needed to fully understand the progression of the neuronal damage after acute ischemic stroke and to evaluate if these biomarkers can provide additive information and how they relate to outcome.
Subject(s)
Brain Ischemia/blood , Brain Ischemia/cerebrospinal fluid , Neurofilament Proteins/blood , Neurofilament Proteins/cerebrospinal fluid , Stroke/blood , Stroke/cerebrospinal fluid , Acute Disease , Adult , Humans , Middle Aged , Phosphorylation , SerumABSTRACT
OBJECTIVE: Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). CNS involvement in lupus is associated with increased morbidity and mortality. Currently, reliable markers for activity in this condition are absent. The goal of this study was to determine the level of the light subunit of the neurofilament triplet protein (NFL) and that of glial fibrillary acidic protein (GFAP) in the cerebrospinal fluid of SLE patients with clinically verified CNS involvement and compare them with the levels in SLE patients without CNS involvement. METHODS: We assessed cerebrospinal fluid obtained from 99 patients with SLE and 99 age-matched controls for the presence of soluble molecules indicating neuronal destruction and astrogliosis-NFL and GFAP, respectively. Patients were evaluated clinically, with magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid analyses, and neuropsychiatric tests. RESULTS: In the group of lupus patients with CNS involvement, intrathecal levels of NFL and GFAP were increased an average of 7-fold (P = 0.0001) and 3-fold (P = 0.05), respectively, compared with the levels in SLE patients without overt CNS disease. Intrathecal levels of NFL correlated significantly with cerebrospinal fluid levels of interleukin-6 (IL-6) (P = 0.005), IL-8 (P = 0.005), pleocytosis (P = 0.05), the albumin ratio (P = 0.0005), and the presence of oligoclonal IgG bands (P = 0.005). Cerebrospinal fluid levels of both NFL and GFAP also showed a significant correlation with MRI abnormalities (P = 0.001). Successful cyclophosphamide treatment of CNS lupus resulted in significantly decreased levels of both proteins; levels of GFAP reached those observed in healthy subjects. CONCLUSION: This study is the first to show biochemical signs of neuronal and astrocytic damage in patients with neuropsychiatric lupus. It is suggested that biochemical markers of brain damage should be used as a followup tool in this patient group.
Subject(s)
Astrocytes/pathology , Lupus Vasculitis, Central Nervous System/cerebrospinal fluid , Lupus Vasculitis, Central Nervous System/pathology , Neurons/pathology , Adolescent , Adult , Aged , Biomarkers/cerebrospinal fluid , Female , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Humans , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Male , Middle Aged , Neurofilament Proteins/cerebrospinal fluidABSTRACT
The aim of the present study was to investigate the potential direct effects of insulin-like growth factor-I (IGF-I) on adult rat hippocampal stem/progenitor cells (AHPs). IGF-I-treated cultures showed a dose-dependent increase in thymidine incorporation, total number of cells, and number of cells entering the mitosis phase. Pretreatment with fibroblast growth factor-2 (FGF-2) increased the IGF-I receptor (IGF-IR) expression, and both FGF-2 and IGF-I were required for maximal proliferation. Time-lapse recordings showed that IGF-I at 100 ng/ml decreased differentiation and increased proliferation of single AHPs. Specific inhibition of mitogen-activated protein kinase kinase (MAPKK), phosphatidylinositol 3-kinase (PI3-K), or the downstream effector of the PI3-K pathway, serine/threonine p70 S6 kinase (p70(S6K)), showed that both the MAPK and the PI3-K pathways participate in IGF-I-induced proliferation but that the MAPK activation is obligatory. These results were confirmed with dominant-negative constructs for these pathways. Stimulation of differentiation was found at a low dose (1 ng/ml) of IGF-I, clonal analysis indicating an instructive component of IGF-I signaling.