Journal of Central Nervous System Disease

Background Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). Methods A total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. Results Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test). Conclusions Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.

[1]  G. Fink,et al.  NG2 and NG2‐positive cells delineate focal cerebral infarct demarcation in rats , 2013, Neuropathology : official journal of the Japanese Society of Neuropathology.

[2]  F. LaFerla,et al.  Astrocytes: Conductors of the Alzheimer disease neuroinflammatory symphony , 2013, Experimental Neurology.

[3]  Per Selnes,et al.  Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid , 2010, Cerebrospinal Fluid Research.

[4]  A. Starkey,et al.  In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases , 2010, Journal of Neuroinflammation.

[5]  Anat Biegon,et al.  Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors , 2010, NeuroImage.

[6]  K. Blennow,et al.  Cerebrospinal fluid biomarkers of white matter lesions – cross‐sectional results from the LADIS study , 2010, European journal of neurology.

[7]  P. Mariën,et al.  Neurobiochemical markers of brain damage in cerebrospinal fluid of acute ischemic stroke patients. , 2010, Clinical chemistry.

[8]  J. Trojanowski,et al.  Total and phosphorylated tau protein as biological markers of Alzheimer’s disease , 2010, Experimental Gerontology.

[9]  K. Blennow,et al.  Subcortical Vascular Dementia Biomarker Pattern in Mild Cognitive Impairment , 2009, Dementia and Geriatric Cognitive Disorders.

[10]  K. Suk,et al.  Role of soluble CD14 in cerebrospinal fluid as a regulator of glial functions , 2009, Journal of neuroscience research.

[11]  M. Brown,et al.  Criteria for a Clinically Informative Serum Biomarker in Acute Ischaemic Stroke: A Review of S100B , 2009, Cerebrovascular Diseases.

[12]  M. Schluep,et al.  Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome. , 2008, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[13]  Daniel Eriksson,et al.  Orthogonal projections to latent structures as a strategy for microarray data normalization , 2007, BMC Bioinformatics.

[14]  K. Blennow,et al.  Neurochemical aftermath of amateur boxing , 2006, Archives of neurology.

[15]  K. Blennow,et al.  CSF –Neurofilament correlates with outcome after aneurysmal subarachnoid hemorrhage , 2006, Neuroscience Letters.

[16]  R. Neumar,et al.  Novel Surrogate Markers for Acute Brain Damage: Cerebrospinal Fluid Levels Corrrelate with Severity of Ischemic Neurodegeneration in the Rat , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  A. Wallin,et al.  The Goteborg MCI study: mild cognitive impairment is a heterogeneous condition , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[18]  T. Neumann-Haefelin,et al.  Evaluation of serum S100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction. , 2005, Archives of neurology.

[19]  V. Selaković,et al.  The increase of neuron-specific enolase in cerebrospinal fluid and plasma as a marker of neuronal damage in patients with acute brain infarction , 2005, Journal of Clinical Neuroscience.

[20]  J. Simpkins,et al.  Transient cerebral ischemia induces site-specific hyperphosphorylation of tau protein , 2004, Brain Research.

[21]  N. Norgren,et al.  Elevated neurofilament levels in neurological diseases , 2003, Brain Research.

[22]  P. Scheltens,et al.  Chemokines in serum and cerebrospinal fluid of Alzheimer's disease patients , 2003, Annals of neurology.

[23]  J. Schwab,et al.  Infiltrating CD14+ monocytes and expression of CD14 by activated parenchymal microglia/macrophages contribute to the pool of CD14+ cells in ischemic brain lesions , 2002, Journal of Neuroimmunology.

[24]  Olaf Gefeller,et al.  Epidemiology of Ischemic Stroke Subtypes According to TOAST Criteria: Incidence, Recurrence, and Long-Term Survival in Ischemic Stroke Subtypes: A Population-Based Study , 2001, Stroke.

[25]  J. Losy,et al.  Monocyte Chemoattractant Protein-1 Is Increased in the Cerebrospinal Fluid of Patients With Ischemic Stroke , 2001, Stroke.

[26]  P. Scheltens,et al.  A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT , 2001, Stroke.

[27]  K. Blennow,et al.  Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke , 2001, Neuroscience Letters.

[28]  K. Blennow,et al.  Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization , 2000, Neuroscience Letters.

[29]  Michael Schroeter,et al.  Inflammation and glial responses in ischemic brain lesions , 1998, Progress in Neurobiology.

[30]  D. Graham,et al.  Increased tau immunoreactivity in oligodendrocytes following human stroke and head injury , 1996, Neuroscience Letters.

[31]  T. Crawford,et al.  Subunit composition of neurofilaments specifies axonal diameter , 1996, The Journal of cell biology.

[32]  K. Blennow,et al.  Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? , 1995, Molecular and chemical neuropathology.

[33]  D. Dewar,et al.  Tau protein is altered by focal cerebral ischaemia in the rat: an immunohistochemical and immunoblotting study , 1995, Brain Research.

[34]  C. Wikkelsø,et al.  A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults , 1994, Journal of Neuroscience Methods.

[35]  H. Adams,et al.  Interphysician agreement in the diagnosis of subtypes of acute ischemic stroke , 1993, Neurology.

[36]  C. Gillberg,et al.  A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children , 1992, Journal of Neuroscience Methods.

[37]  K. Haglid,et al.  Determination of S‐100 and Glial Fibrillary Acidic Protein Concentrations in Cerebrospinal Fluid After Brain Infarction , 1991, Stroke.

[38]  J. Marler,et al.  Measurements of acute cerebral infarction: a clinical examination scale. , 1989, Stroke.

[39]  B. Winblad,et al.  Brain and Plasma Proteins in Spinal Fluid as Markers for Brain Damage and Severity of Stroke , 1984, Stroke.

[40]  Kanefusa Kato,et al.  Neuron-specific enolase and S-100 protein levels in cerebrospinal fluid of patients with various neurological diseases , 1983, Journal of the Neurological Sciences.

[41]  Y. Itoyama,et al.  Myelin basic protein demonstrated immunocytochemically in oligodendroglia prior to myelin sheath formation. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Maria Thom,et al.  Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study. , 2011, Brain : a journal of neurology.

[43]  K. Blennow,et al.  Cerebrospinal fluid matrix metalloproteinases and tissue inhibitor of metalloproteinases in combination with subcortical and cortical biomarkers in vascular dementia and Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[44]  Manfred Herrmann,et al.  Brain derived proteins as markers of acute stroke: their relation to pathophysiology, outcome prediction and neuroprotective drug monitoring. , 2003, Restorative neurology and neuroscience.

[45]  T. Sugawara,et al.  Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. , 2002, Journal of neurotrauma.

[46]  K. Blennow,et al.  Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke. , 2000, Journal of Alzheimer's disease : JAD.

[47]  P. Morell,et al.  Myelin Formation, Structure and Biochemistry , 1999 .

[48]  M. Kornitzer,et al.  The World Health Organization MONICA Project (Monitoring trends and determinants in cardiovascular disease): A major international Collaboration , 1988 .

[49]  Principal Investigators,et al.  The World Health Organization MONICA project (monitoring trends and determinants in cardiovascular disease): a major international collabaration , 1988 .