myelin-basic-protein and Brain-Damage--Chronic

Our previous study showed that treatment with alpha-phenyl-n-tert-butyl-nitrone (PBN) after exposure to lipopolysaccharide (LPS) reduced LPS-induced white matter injury in the neonatal rat brain. The object of the current study was to further examine whether PBN has long-lasting protective effects and ameliorates LPS-induced neurological dysfunction. Intracerebral (i.c.) injection of LPS (1 mg/kg) was performed in postnatal day (P) 5 Sprague Dawley rat pups and PBN (100 mg/kg) or saline was administered intraperitoneally 5 min after LPS injection. The control rats were injected (i.c.) with sterile saline. Neurobehavioral tests were carried out from P3 to P21, and brain injury was examined after these tests. LPS exposure resulted in severe brain damage, including enlargement of ventricles bilaterally, loss of mature oligodendrocytes, impaired myelination as indicated by the decrease in myelin basic protein immunostaining, and alterations in dendritic processes in the cortical gray matter of the parietal cortex. Electron microscopic examination showed that LPS exposure caused impaired myelination as indicated by the disintegrated myelin sheaths in the juvenile rat brain. LPS administration also significantly affected neurobehavioral functions such as performance in righting reflex, wire hanging maneuver, cliff avoidance, negative geotaxis, vibrissa-elicited forelimb-placing test, beam walking, and gait test. Treatment with PBN, a free radical scavenger and antioxidant, provided protection against LPS-induced brain injury and associated neurological dysfunction in juvenile rats, suggesting that antioxidation might be an effective approach for therapeutic treatment of neonatal brain injury induced by infection/inflammation.

Topics: Animals; Animals, Newborn; Brain; Brain Damage, Chronic; Central Nervous System Bacterial Infections; Cyclic N-Oxides; Disease Models, Animal; Female; Gait Disorders, Neurologic; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Leukomalacia, Periventricular; Lipopolysaccharides; Male; Movement Disorders; Myelin Basic Protein; Nerve Fibers, Myelinated; Neuroprotective Agents; Oligodendroglia; Pregnancy; Rats; Rats, Sprague-Dawley; Recovery of Function; Reflex

White matter lesions are thought to result from chronic cerebral ischemia and constitute a core pathology of subcortical vascular dementia. This rarefaction has been known to be associated with microglial activation. We investigated whether minocycline, a microglial inhibitor, attenuates the white matter damage induced by chronic cerebral hypoperfusion that is used as a model of vascular dementia. Male Wistar rats were subjected to bilateral, permanent occlusion of the common carotid arteries (BCCAO) to induce chronic cerebral hypoperfusion. Minocycline or saline was injected daily for 2 weeks after BCCAO. In the corpus callosum and the optic tract, white matter damage observed with Klüver-Barrera staining was significantly attenuated in the minocycline-treated group compared to saline-treated controls. In control rats, immunoreactivities of major basic protein (MBP), Ox-42 as a microglial marker, and matrix metalloproteinase (MMP)-2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Co-expression of Ox-42 and MMP-2 was confirmed by double immunofluorescence histochemistry. Our results suggest that chronic treatment with minocycline could be protective against at least some ischemic white matter damage, and its mechanism may be related to suppressing microglial activation.

Topics: Analysis of Variance; Animals; Brain Damage, Chronic; CD11b Antigen; Corpus Callosum; Dementia, Vascular; Diagnostic Imaging; Disease Models, Animal; Drug Administration Schedule; Glial Fibrillary Acidic Protein; Immunohistochemistry; Male; Matrix Metalloproteinase 2; Minocycline; Myelin Basic Protein; Rats; Rats, Wistar; Visual Pathways

Biochemical markers of acute neuronal injury may aid in the diagnosis and management of acute ischemic stroke. Serum samples from the National Institute for Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator Stroke Study were analyzed for the presence of 4 biochemical markers of neuronal, glial, and endothelial cell injury. These biochemical markers, myelin basic protein (MBP), neuron-specific enolase (NSE), S100beta, and soluble thrombomodulin, were studied for an association with initial stroke severity, infarct volume, and functional outcome.. In the original NINDS study, serum samples were drawn from all patients on presentation to the Emergency Department and at approximately 2 and 24 hours after initiation of study therapy. In this analysis, stored serum samples were available for 359 patients; 107 patients had samples for all 3 time points. Serum marker concentrations were measured by ELISA techniques. We examined the relation between serum concentrations of each marker and the degree of baseline neurological deficit, functional outcome, and infarct size on computed tomography at 24 hours and the effect of fibrinolytic therapy.. Higher 24-hour peak concentrations of MBP, NSE, and S100beta were associated with higher National Institutes of Health Stroke Scale baseline scores (r=0.186, P<0.0001; r=0.117, P=0.032; and r=0.263, P<0.0001, respectively). Higher peak concentrations of MBP and S100beta (r=0.209, P<0.0001; r=0.239, P<0.0001) were associated with larger computed tomography lesion volumes. Patients with favorable outcomes had smaller changes in MBP and S100beta (P<0.05) concentrations in the first 24 hours. Soluble thrombomodulin was not associated with any severity or outcome measure.. This study corroborates previous work demonstrating correlations of MBP, NSE, and S100beta with clinical and radiographic features in acute stroke. Despite significantly better outcomes in the tissue plasminogen activator-treated group, we found no difference in the early release of the 4 biomarkers between treatment groups. Further study will define the role of biomarkers in acute stroke management and prognostication.

Topics: Acute Disease; Adult; Aged; Biomarkers; Brain Damage, Chronic; Brain Infarction; Brain Ischemia; Double-Blind Method; Endothelial Cells; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myelin Basic Protein; Nerve Growth Factors; Neuroglia; Neurons; Phosphopyruvate Hydratase; Randomized Controlled Trials as Topic; Recombinant Proteins; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Thrombomodulin; Time Factors; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Treatment Outcome

Hydrocephalus is characterised by elevated intracranial pressure (ICP) and gives rise to brain damage. The aim of this study was to investigate the significance of brain specific proteins as markers in the evaluation of brain damage in hydrocephalus. Therefore we determined the levels of four brain specific proteins in cerebrospinal fluid (CSF) and serum of symptomatic hydrocephalic patients.. During 41 CSF shunt-operations (both primarily placed shunts and shunt-revisions) CSF and blood samples were obtained and analysed for neuron-specific enolase (NSE), S-100b, glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). The results were compared with an age-matched control group. Patients with varying clinical symptoms, denoting different levels of increased intracranial pressure prior to surgery, were included in this study.. We observed significantly increased CSF-levels of S-100b and GFAP in the hydrocephalic patients, whereas NSE and MBP were markedly increased only in patients with very severe symptoms. Serum levels of all proteins were only minimally increased and did not correlate with CSF-levels. The slightly elevated levels of CSF-NSE in most of the patients suggest only subtle neuronal damage, which is not related to permanent neurological symptoms. The elevated levels of S-100b and GFAP are indicative of a reactive astrogliosis, which has also been demonstrated in histopathological studies. No demyelination seems to occur, according to the normal levels of MBP observed in this study.. Although CSF levels of brain specific proteins are elevated in hydrocephalic patients, indicating brain damage due to hydrocephalus, neither CSF- nor serum-concentrations of brain specific proteins seem to be valuable tools in the clinical evaluation of the severity of hydrocephalus.

Topics: Adolescent; Brain Damage, Chronic; Child; Child, Preschool; Female; Glial Fibrillary Acidic Protein; Humans; Hydrocephalus; Male; Myelin Basic Protein; Nerve Growth Factors; Phosphopyruvate Hydratase; Predictive Value of Tests; Reproducibility of Results; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Severity of Illness Index

We questioned whether neuron-specific enolase (NSE) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) in the first 72 hours of life are correlated with the neurologic condition of asphyxiated full-term infants in the neonatal period and at 1 year of age.. Sixty-nine asphyxiated infants were studied with serial neurologic examination, cranial ultrasonography, and neurologic follow-up. CSF samples were obtained by lumbar puncture at 12 and 72 hours of life. NSE was measured by enzyme immunoassay, and MBP was measured by radioimmunoassay.. Twenty infants had no neonatal encephalopathy and 49 exhibited different stages of encephalopathy. NSE and MBP concentrations in CSF at 12 and 72 hours of life were related to the degree of neonatal encephalopathy. Neither NSE nor MBP levels were correlated with any perinatal factors. Infants with documented brain injury had the highest concentrations of both NSE and MBP. The concentrations of these two biochemical markers at both 12 and 72 hours correlated with adverse outcome (death or cerebral palsy at 1 year). Based on a receiver operating characteristics curve analysis for any given specificity, NSE at 12 hours was a more accurate marker than MBP at either 12 or 72 hours for distinguishing infants with motor impairment at age 1 year from infants with normal outcome at the same age.. Our findings suggest that NSE and MBP are reliable biochemical markers for early estimates of hypoxic-ischemic brain damage in asphyctic full-term newborns, NSE being superior to MBP.

Topics: Asphyxia Neonatorum; Biomarkers; Brain Damage, Chronic; Brain Ischemia; Gestational Age; Humans; Hypoxia, Brain; Infant, Newborn; Myelin Basic Protein; Neurologic Examination; Neuroradiography; Paraplegia; Phosphopyruvate Hydratase; Prospective Studies; Quadriplegia

We measured the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with various kinds of tumors, including malignant tumors, using radioimmunoassay. The CSF had been obtained by lumbar puncture through an Ommaya reservoir or a shunt device placed in the lateral ventricle. The level of MBP was high (> 4 ng/ml) in the patients with meningeal dissemination of malignant tumors, but in those who showed a good response to chemotherapy and/or radiation, it decreased or returned to the normal level, with improvement on the computed tomography and magnetic resonance imaging, cytological, general CSF, and neurological findings. Of seven malignant gliomas without CSF dissemination, six showed an elevated level of MBP before selective intra-arterial chemotherapy with a combination of etoposide and cisplatin administered via a microcatheter placed at A1, M1, P1-P2, and the basilar top. All CSF specimens obtained during the period of the intra-arterial chemotherapy showed an abnormally high (> 4 ng/ml) level of MBP that exceeded the prechemotherapy level. The MBP level decreased or returned to normal in the patients with a good response to chemotherapy after intra-arterial chemotherapy. In some patients with multiple metastatic brain tumors, the MBP level was elevated before treatment and returned to normal after treatment (surgical removal, chemotherapy, and/or irradiation) in all except one. Thus, there was a clear correlation between the timing of treatment and changes in imaging studies and MBP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Astrocytoma; Biomarkers, Tumor; Brain Damage, Chronic; Brain Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Cranial Irradiation; Etoposide; Female; Follow-Up Studies; Glioblastoma; Humans; Infusions, Intra-Arterial; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Myelin Basic Protein; Treatment Outcome

Raised ventricular CSF myelin basic protein (MBP) concentration has been evidenced in 17 shunted hydrocephalic patients. Contemporary evaluation both from ventricular and lumbar CSF samples showed a concentration ratio of 20:1. In all cases the raised values of ventricular CSF concentration of MBP demonstrated a significant decrease after shunt operation. This preliminary report suggests that this marker is an important index of actual brain damage in hydrocephalus and could be taken in account for the indication of shunt operation.

Topics: Adolescent; Adult; Aged; Biomarkers; Brain Damage, Chronic; Child, Preschool; Humans; Hydrocephalus; Intracranial Pressure; Middle Aged; Myelin Basic Protein; Ventriculoperitoneal Shunt

Cerebrospinal fluid (CSF) myelin basic protein (MBP) was measured blind by double antibody competitive inhibition radioimmunoassay (RIA) in 20 children who had seizures and 17 children with hydrocephalus. MBP values correlated with clinical outcome and mean maximum intracranial pressure (ICP) in the hydrocephalic group, and with type of convulsion in the epileptic group. A value of 20ng/ml or more was regarded as significantly raised. A significant rise in MBP levels could be demonstrated in those with ICP alone and in patients with additional problems, whose levels tended to be even higher. Hydrocephalic children with normal ICP and children with seizures had similar normal MBP levels, and in the latter group clinical outcome was not related to MBP levels. For individual patients CSF MBP is of little value as a prognostic indicator, or as a method of quantifying cerebral damage.

Topics: Adolescent; Brain Damage, Chronic; Child; Child, Preschool; Epilepsy; Female; Humans; Hydrocephalus; Infant; Intracranial Pressure; Male; Myelin Basic Protein; Radioimmunoassay