myelin-basic-protein and Subarachnoid-Hemorrhage

Neuroinflammation has been reported to be associated with white matter injury (WMI) after subarachnoid hemorrhage (SAH). As the main resident immune cells of the brain, microglia can be activated into proinflammatory and anti-inflammatory phenotypes. Toll-like receptor 4 (TLR4), expressed on the surface of the microglia, plays a key role in microglial inflammation. However, the relationship between TLR4, microglial polarization, and WMI following SAH remains unclear. In this study, a total of 121 male adult C57BL/6 wild-type (WT) mice, 20 WT mice at postnatal day 1 (P1), and 41 male adult TLR4 gene knockout (TLR4-/-) mice were used to investigate the potential role of TLR4-induced microglial polarization in early WMI after SAH by radiological, histological, microstructural, transcriptional, and cytological evidence. The results indicated that microglial inflammation was associated with myelin loss and axon damage, shown as a decrease in myelin basic protein (MBP), as well as increase in degraded myelin basic protein (dMBP) and amyloid precursor protein (APP). Gene knockout of TLR4 revised microglial polarization toward the anti-inflammatory phenotype and protected the white matter at an early phase after SAH (24 h), as shown through reduction of toxic metabolites, preservation of myelin, reductions in APP accumulation, reductions in white matter T

Topics: Animals; Anti-Inflammatory Agents; Brain Injuries; Inflammation; Male; Mice; Mice, Inbred C57BL; Microglia; Myelin Basic Protein; Neuroinflammatory Diseases; Subarachnoid Hemorrhage; Toll-Like Receptor 4; White Matter

Myelin basic protein (MBP) is the second most abundant protein in central nervous system myelin. Since the 1980s, it has been regarded as a marker of brain tissue injury in both trauma and disease. There have been no recent reports regarding MBP in aneurysmal subarachnoid haemorrhage (SAH).. One hundred four SAH patients with ruptured aneurysms underwent endovascular treatment within 24 h of rupture, and 156 blood samples were collected: 104 on days 0-3, 32 on days 4-6 and 20 on days 9-12 post-SAH. MBP levels were assayed using ELISA and compared with the clinical status on admission, laboratory results, imaging findings and treatment outcome at 3 months.. MBP levels on days 0-3 post-SAH were significantly higher among poor outcome patients (p < 0.001), non-survivors (p = 0.005), patients who underwent intracranial intervention (p < 0.001) and patients with intracerebral haemorrhage (ICH; p < 0.001). On days 4-6 post-SAH, significantly higher levels were found following intracranial intervention (p = 0.009) and ICH (p = 0.039). There was clinically relevant correlation between MBP levels on days 0-3 post-SAH and 3-month Glasgow Outcome Scale (cc = - 0.42) and also ICH volume (cc = 0.48). All patients who made a full recovery had MBP levels below detection limit on days 0-3 post-SAH. Following endovascular aneurysm occlusion, there was no increase in MBP in 86 of the 104 patients investigated (83%).. The concentration of MBP in peripheral blood after intracranial aneurysm rupture reflects the severity of the brain tissue injury (due to surgery or ICH) and correlates with the treatment outcome. Endovascular aneurysm occlusion was not followed by a rise in MBP in most cases, suggesting the safety of this technique.

Topics: Adult; Aged; Aneurysm, Ruptured; Biomarkers; Blood Vessel Prosthesis Implantation; Brain; Endovascular Procedures; Female; Glasgow Outcome Scale; Humans; Male; Middle Aged; Myelin Basic Protein; Postoperative Complications; Subarachnoid Hemorrhage

Increased plasma copeptin concentrations are related to poor prognosis after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess prognostic significance of plasma copeptin detection compared with glial fibrillary astrocyte protein, myelin basic protein, S100B, phosphorylated axonal neurofilament subunit H, neuron-specific enolase, tau and ubiquitin carboxyl-terminal hydrolase L1 in aSAH.. We detected plasma concentrations of the aforementioned biomarkers in 105 healthy controls using ELISA. Their predictive ability for symptomatic cerebral vasospasm and 6-month poor outcome (Glasgow Outcome Scale score of 1-3) were compared.. Plasma concentrations of the preceding biomarkers were highly correlated with World Federation of Neurological Surgeons subarachnoid hemorrhage scale (WFNS) scores as well as were significantly higher in patients with symptomatic cerebral vasospasm than in those without symptomatic cerebral vasospasm and in patients with poor outcome than in those with good outcome. In terms of area under receiver operating characteristic curve, their predictive value for symptomatic cerebral vasospasm and 6-month poor outcome was in the range of WFNS scores. Plasma copeptin concentration, but not plasma concentrations of other biomarkers, statistically significantly improved the predictive performance of WFNS scores.. Copeptin in plasma might have the potential to be a useful prognostic biomarker for aSAH.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Female; Gene Expression; Glial Fibrillary Acidic Protein; Glycopeptides; Humans; Intracranial Aneurysm; Male; Middle Aged; Myelin Basic Protein; Neurofilament Proteins; Phosphopyruvate Hydratase; Predictive Value of Tests; Prognosis; Prospective Studies; S100 Calcium Binding Protein beta Subunit; Subarachnoid Hemorrhage; tau Proteins; Ubiquitin Thiolesterase; Vasospasm, Intracranial

Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.

Topics: Animals; CA1 Region, Hippocampal; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Disease Models, Animal; Long-Term Potentiation; Magnetic Resonance Imaging; Male; Microscopy, Electron, Transmission; Microtubule-Associated Proteins; Myelin Basic Protein; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Receptors, AMPA; Subarachnoid Hemorrhage

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm.

Topics: Adult; Aged; Aged, 80 and over; Cerebral Infarction; Female; GPI-Linked Proteins; Humans; Male; Membrane Proteins; Metalloproteins; Middle Aged; Myelin Basic Protein; Neoplasm Proteins; Predictive Value of Tests; Spinal Puncture; Subarachnoid Hemorrhage; Vasospasm, Intracranial

No marker that reflects and predicts brain injury due to subarachnoid hemorrhage (SAH) and cerebral vasospasm has been reported. We hypothesized that membrane-bound tissue factor (mTF) and thrombin-antithrombin III complex (TAT) in the cerebrospinal fluid (CSF) of patients with SAH become markers indicating brain injury. To evaluate the hypothesis, we correlated levels of mTF and TAT in the CSF of patients with SAH with clinical severity, the degree of SAH, and outcome.. We assayed CSF mTF, TAT and myelin basic protein (MBP) in patients with SAH at intervals that included days 0 to 4 and days 5 to 9 after ictus. Classification of clinical severity of disease on admission was based on Hunt and Hess grade, degree of SAH on CT on Fisher's grading, and outcome 3 months after SAH on the Glasgow Outcome Scale.. In the interval from days 0 to 4, mTF and TAT correlated with Hunt and Hess and Fisher grades, and occurrence of cerebral infarction due to vasospasm. Only mTF correlated significantly in this period with outcome. TAT, mTF, and MBP all correlated significantly with each other. From days 5 to 9, only mTF correlated with cerebral infarction, infarction volume, MBP levels, and outcome.. Both mTF and TAT reflected brain injury from SAH and predicted vasospasm, though mTF was more sensitive and a better predictor of outcome. Unlike mTF, TAT did not correlate with vasospasm during the interval when it most commonly occurs, which raised doubt about thrombin activation as a cause.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; Biomarkers; Cerebral Infarction; Female; Hospitalization; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myelin Basic Protein; Osmolar Concentration; Peptide Hydrolases; Severity of Illness Index; Subarachnoid Hemorrhage; Thromboplastin; Tomography, X-Ray Computed; Treatment Outcome

In 44 patients undergoing neurosurgical procedures for intracranial tumors, subarachnoid hemorrhage, or spinal and peripheral nerve lesions, serum myelin basic protein (MBP) immunoreactivity was measured preoperatively and serially in the first 10 postoperative days. The double-antibody radioimmunoassay method was used, with a detection limit of 2.5 ng/ml in serum. Clinical evaluation was carried out at admission and on successive days during the period of neurosurgical management; outcome was assessed later. In the early postoperative phase, there was a fall in MBP immunoreactivity in all groups of patients. In the groups with intracranial tumor and subarachnoid hemorrhage, there was a subsequent rise in MBP immunoreactivity before the end of the 10-day period, which was not found in the group with spinal and peripheral nerve lesions.

Topics: Adenoma; Brain Neoplasms; Central Nervous System Diseases; Female; Glioma; Humans; Male; Meningioma; Middle Aged; Myelin Basic Protein; Radioimmunoassay; Spinal Cord Diseases; Spinal Diseases; Subarachnoid Hemorrhage