myelin-basic-protein and Cerebral-Infarction

In experimental models of stroke, inflammation appears to contribute to cerebral ischemic injury. Clinical trials that are aimed at limiting the postischemic inflammatory response, however, have thus far had disappointing results. These clinical failures probably reflect the fact that there has been insufficient preclinical data and inadequate trial design, rather than provide evidence against a role for inflammation in ischemic brain injury.

Topics: Animals; Autoantigens; Blood-Brain Barrier; Cerebral Infarction; Cytokines; Encephalitis; Humans; Leukocytes; Myelin Basic Protein

To study biological effect of recombinant human erythropoietin (RhEPO) on the expression of oligodendrocyte in the neuron glia antigen 2(NG2), Nogo receptor-interacting protein 1(LINGO-1), myelin basic protein (MBP) and myelin associated glycoprotein (MAG), and to explore the protective mechanism of RhEPO for oligodendrocyte after cerebral infarction.. Experimental rats were randomly divided into the treatment group (RhEPO at a dose of 3 000 U/kg) or saline control group. Both groups received intraperitoneal injection of RhEPO after cerebral ischemia in 30 min, 3 h, 6 h, 12 h and 24 h, which was administered daily for 7 days. The modified neurological severity score (mNSS) and histology were analyzed, and immunohistochemistry was used to detect the protein expression of NG2, MAG, MBP and LINGO-1.. The overall mNSS of RhEPO treatment group significantly decreased compared with the saline control group on the seventh day after cerebral infarction (P<0.05). Such treatment effect was more obvious in the treatment group at 30 min and 3 h (P<0.01). Compared with the saline control group, the numbers of NG2 positive cells increased in RhEPO treatment group. In contrast, the expression of LINGO-1 protein significantly decreased (P<0.05), with a dramatic decrease observed at 30 min and 3 h (P<0.01). However, the expression of MBP protein decreased more significantly in saline control group, while the level of the MAG protein expression increased. The differences were statistically significant (P<0.05), especially at 30 min (P<0.01).. After cerebral ischemia, RhEPO promotes the proliferation of NG2 positive cells, and inhibits the expression of LINGO-1 and MAG proteins. RhEPO improves the proliferation and differentiation of oligodendrocyte precursor cells, which in turn protects neuronal function, particularly at the early phase of ischemia.

Topics: Animals; Antigens; Cell Proliferation; Cerebral Infarction; Erythropoietin; Humans; Membrane Proteins; Myelin Basic Protein; Myelin-Associated Glycoprotein; Nerve Tissue Proteins; Neurons; Oligodendroglia; Proteoglycans; Random Allocation; Rats; Recombinant Proteins; Time Factors

Topics: Acute Disease; Carbon Monoxide Poisoning; Cerebral Cortex; Cerebral Hemorrhage; Cerebral Infarction; Diffusion Magnetic Resonance Imaging; Globus Pallidus; Humans; Iron; Myelin Basic Protein; Nerve Fibers, Myelinated; Prospective Studies

Neonatal hypoxic-ischemic (HI) white matter injury is a major contributor to chronic neurological dysfunction. Immature oligodendrocytes (OLGs) are highly vulnerable to HI injury. As little is known about in vivo OLG repair mechanisms in neonates, we studied whether new OLGs are generated after HI injury in P7 rats. Rats received daily BrdU injections at P12-14 or P21-22 and sacrificed at P14 to study the level of cell proliferation or at P35 to permit dividing OLG precursors to differentiate. In P14 HI-injured animals, the number of BrdU+ cells in the injured hemisphere is consistently greater than controls. At P35, sections were double-labeled for BrdU and markers for OLGs, astrocytes, and microglia. Double-labeled BrdU+/myelin basic protein+ and BrdU+/carbonic anhydrase+ OLGs are abundant in the injured striatum, corpus callosum, and the infarct core. Quantitative studies show four times as many OLGs are generated from P21-35 in HI corpora callosa than controls. Surprisingly, the infarct core contains many newly generated OLGs in addition to hypertrophied astrocytes and activated microglia. These glia and non-CNS cells may stimulate OLG progenitor proliferation or induce their migration. At P35, astrogliosis and microgliosis are dramatic ipsilaterally but only a few microglia and some astrocytes are BrdU+. This finding indicates microglial and astrocytic hyperplasia occurs shortly after HI but before the P21 BrdU injections. Although the neonatal brain undergoes massive cell death and atrophy the first week after injury, it retains the potential to generate new OLGs up to 4 weeks after injury within and surrounding the infarct.

Topics: Animals; Animals, Newborn; Astrocytes; Atrophy; Biomarkers; Bromodeoxyuridine; Carbonic Acid; Cell Count; Cell Death; Cell Differentiation; Cell Division; Cerebral Infarction; Disease Models, Animal; Gliosis; Hypoxia-Ischemia, Brain; Myelin Basic Protein; Nerve Fibers, Myelinated; Oligodendroglia; Rats; Rats, Sprague-Dawley; Stem Cells

Breakdown of the blood-brain barrier during stroke allows central nervous system antigens to leak into the systemic circulation and allows circulating leukocytes access to the brain. Encounter of central nervous system antigens by the peripheral immune system can be capitalized on to modulate the postischemic inflammatory response and potentially improve outcome from stroke.. Male Lewis rats were tolerized to myelin basic protein (MBP) or ovalbumin (OVA) and subjected to 3 hours of middle cerebral artery occlusion (MCAO) or used as splenocyte donors for immunologically naive animals undergoing MCAO. Infarct size was determined at 24 hours by 2,3,5-triphenyltetrazolium chloride staining. In separate studies, mononuclear cells were removed from the brains of animals after MCAO for enzyme-linked immunospot (ELISPOT) assay and flow cytometry.. Median infarct volume in animals tolerized to MBP and those receiving splenocytes from MBP-tolerized donors was less than in animals tolerized to OVA and those receiving splenocytes from OVA-tolerized donors (87.7+/-54.9 versus 148+/-61.6 mm3 [P=0.01] and 89.2+/-77.5 versus 153+/-77.1 mm3 [P=0.05], respectively). There was an increase in the number of transforming growth factor-beta1-secreting mononuclear cells in MBP-tolerized animals undergoing sham surgery (P=0.001) as well as in ischemic animals 48 hours (P=0.02) and 336 hours (P=0.04) after stroke. A distinct subset of gammadelta T cells was present in the brains of MBP-tolerized but not control animals after stroke.. Immunologic tolerance and its neuroprotective effects can be transferred to naive animals and appear to be related to antigen-specific induction of transforming growth factor-beta1.

Topics: Administration, Intranasal; Adoptive Transfer; Animals; Brain Ischemia; Cell Count; Cerebral Infarction; Cytoprotection; Disease Progression; Immune Tolerance; Inflammation; Lymphocytes; Male; Myelin Basic Protein; Nasal Mucosa; Rats; Rats, Inbred Lew; Spleen

This study examines the alteration of oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes (OLGs) and myelination after focal ischemia in the rat brain. Adult male Sprague-Dawley rats were subjected to 90-min occlusion of the middle cerebral artery, followed by reperfusion time of up to 2 weeks. The infarct core showed a rapid and progressive decrease in the number of OPCs, OLGs, as well as the myelin density after 48 h of recirculation. The peri-infarct area exhibited a moderate reduction in the number of OLGs and the myelin density with a slight increase in the number of OPCs at 48 h of recirculation. Subsequently, a steady increase in the number of OPCs and a gradual recovery of the number of OLGs were noted in the peri-infarct area, which were accompanied by a gradual restoration of the myelin density, resulting in almost complete recovery of myelin density at 2 weeks of recirculation. OPCs in the peri-infarct area showed characteristic morphological changes such as mitotic figures, monopolar or bipolar shapes, and hypertrophied cell bodies and processes, all indicating active cell proliferation and migration. These findings suggest that the upregulation of OPCs may contribute to replenishment of OLGs and resultant remyelination in the peri-infarct area after ischemic insult.

Topics: Animals; Antigens; Biomarkers; Cerebral Infarction; Functional Laterality; Glutathione S-Transferase pi; Glutathione Transferase; Immunohistochemistry; Isoenzymes; Male; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Proteoglycans; Rats; Rats, Sprague-Dawley; Stem Cells; Time Factors; Up-Regulation

Cerebral white matter (WM) lesions are observed frequently in human ischemic cerebrovascular disease and have been thought to contribute to cognitive impairment. This type of lesion can be experimentally induced in rat brains under chronic cerebral hypoperfusion by the permanent occlusion of both common carotid arteries. However, it remains uncertain whether chronic ischemia can damage both the gray and white matter, and whether it can induce demyelination with or without axonal damage. Therefore, we examined axonal damage using immunohistochemistry for the amyloid beta/A4 precursor protein (APP), chromogranin A (CgA) and demyelination using immunohistochemistry for the encephalitogenic peptide (EP) in this model. Severe WM lesions such as vacuolation and the loss of nerve fibers appeared in the optic nerve and optic tract after 3 days of ligation, and less intense changes were observed in the corpus callosum, internal capsule, and fiber bundles of the caudoputamen after 7 days with Klüver-Barrera and Bielschowsky staining. These WM lesions persisted even after 30 days. The APP, CgA, and EP-immunopositive fibers increased in number from 1 to 30 days after the ligation in the following WM regions: the optic nerve, optic tract, corpus callosum, internal capsule, and fiber bundles of the caudoputamen. In contrast, only a few APP, CgA, or EP-immunopositive fibers were detected in the gray matter regions, including the cerebral cortex and hippocampus. These results indicate that the WM is more susceptible to chronic cerebral hypoperfusion than the gray matter, with an involvement of both axonal and myelin components. Furthermore, immunohistochemistry for APP, CgA, and EP is far superior to routine histological staining in sensitivity and may become a useful tool to investigate WM lesions caused by various pathoetiologies.

Topics: Amyloid beta-Protein Precursor; Animals; Axons; Brain Ischemia; Cerebral Infarction; Chromogranin A; Chromogranins; Chronic Disease; Demyelinating Diseases; Immunohistochemistry; Male; Myelin Basic Protein; Nerve Fibers, Myelinated; Peptide Fragments; Prosencephalon; Rats; Rats, Wistar; Wallerian Degeneration

Although oligodendrocytes are vulnerable to focal cerebral ischemia, remyelination of denuded or regenerating axons in the peri-infarct area has been observed in the central nervous system. We studied the expression of myelin basic protein (MBP), a major component of central nervous system myelin, in peri-infarct areas in adult rat brain after transient middle cerebral artery occlusion (MCAO) and correlated it to the expression of the growth-associated protein-43 (GAP-43), a marker for axonal regeneration and sprouting, using non-radioactive in situ hybridization techniques. Within the infarct, MBP messenger RNA (mRNA) had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin oligodendrocyte glycoprotein (MOG) immunohistochemistry, appeared structurally intact until day 3. Peri-infarct oligodendrocytes increased their expression of MBP mRNA from 24 h to maximal levels at day 7, corresponding to the appearance of process-bearing MBP and occasional MOG-immunoreactive oligodendrocytes in parallel sections. Quantitative analysis revealed significant increases in the density of oligodendrocytes (up to 7.6-fold) and in the level of MBP mRNA expressed by individual cells. Parallel sections showed that increased expression of GAP-43 mRNA in neurons was concomitant to MBP mRNA upregulation in oligodendrocytes. While the mechanisms regulating oligodendrocyte survival and myelination signals are not clear at this point, axonal sprouting could putatively serve as a stimulus for the upregulation of oligodendrocyte cell numbers, differentiation state, and/or active myelination in the peri-infarct areas.

Topics: Animals; Brain; Brain Ischemia; Cerebral Infarction; GAP-43 Protein; Gene Expression Regulation; Immunohistochemistry; In Situ Hybridization; Male; Myelin Basic Protein; Myelin Sheath; Nerve Degeneration; Rats; Rats, Inbred SHR; RNA, Messenger; Transcription, Genetic; Up-Regulation

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

The ability of putative neuroprotective compounds to protect against white matter injury remains poorly investigated due to the lack of suitable methods for assessing white matter injury. This study was therefore designed to investigate the utility of Tau 1 (oligodendrocytes/axons), myelin basic protein (MBP; myelin) and amyloid precursor protein (APP; axons) immunohistochemistry in assessing white matter injury at various times following middle cerebral artery occlusion (MCAO) in the rat. Focal cerebral, ischaemia was induced in halothane-anaesthetised rats using an intraluminal thread model. At 24 h, 1 and 2 weeks following MCAO, white matter injury was assessed using Tau 1, APP, MBP and Luxol-fast blue staining and neuronal injury with cresyl fast violet (CFV). In histologically normal tissue MBP immunoreactivity was detected in myelinated fibre tracts, while Tau 1 and APP were axonally located. At 24 h following permanent MCAO, MBP, and Tau 1 staining remained relatively unchanged within the myelin and axonal compartments of the ischaemic region. In contrast, increased Tau 1 staining was apparent in oligodendrocytes within ischaemic tissue, while APP accumulated in axons surrounding the lesion. At 1 and 2 weeks following transient MCAO, Tau 1 and APP staining was markedly decreased within ischaemic tissue. Marked reduction in MBP levels within ischaemic tissue were not detected until 2 weeks following MCAO. The area of axonal injury as assessed by reduced Tau 1 or APP staining correlated with the area of neuronal damage as assessed by CFV staining. This study shows that MBP, Tau 1 and APP immunohistochemistry can be utilised to assess myelin and axonal integrity following sustained ischaemia using standard image analysis techniques.

Topics: Amyloid beta-Protein Precursor; Animals; Biomarkers; Brain Ischemia; Cell Death; Cerebral Cortex; Cerebral Infarction; Immunohistochemistry; Male; Myelin Basic Protein; Nerve Degeneration; Nerve Fibers, Myelinated; Rats; Rats, Sprague-Dawley; tau Proteins

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

The expression of encephalitogenic peptide (EP), a 68-86 amino acid sequence of guinea pig myelin basic protein (MBP), was investigated in autopsied brains with focal cerebral damage or with diffuse white matter (WM) lesions. EP immunoreactive fibers were distributed in parallel with fibers immunoreactive for amyloid protein precursor (APP), an indicator of WM damages. EP was expressed in the periphery of cerebral infarctions and hematoma in the acute and subacute stages, but was also distributed in diffuse WM lesions due to heterogeneous causes. These data indicate that EP epitopes are exposed specifically in ongoing WM damages, and that the destruction of myelin occurs sporadically in diffuse WM lesions of varying intensity.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Animals; Autopsy; Brain; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Circulation; Dementia; Guinea Pigs; Hematoma; Humans; Myelin Basic Protein; Myelin Sheath; Nerve Fibers; Peptide Fragments

Myelin basic protein (MBP) was measured in the serum and CSF of patients with acute cerebrovascular disease (CVD, 34 cases), demyelinating disorders (DMD, 30 cases) and other neurological diseases (OND, 26 cases) by using a double antibody radioimmunoassay (RIA). Patients with acute CVD had a mean serum MBP concentration and positivity rate much higher than those with DMD and OND. The differences were significant (P < 0.05). In CSF, MBP levels in patients with acute CVD and patients with DMD were significantly greater than those in OND patients (P < 0.05). The results also show that there was a linear relationship between the CSF MBP levels and the serum MBP levels in patients with acute CVD (r = 0.72, P < 0.01), but no such relationship in patients with DMD and OND. The amount of serum MBP was also significantly correlated to the severity of acute CVD, to the level of consciousness disorder and limb paralysis, and to the extent and site of the cerebral lesion at CT-scan (P < 0.05). This study shows that the measurement of brain specific MBP in serum as a marker of cerebral damage may have clinical value in the diagnosis and prognosis of patients with CVD.

Topics: Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Humans; Multiple Sclerosis; Myelin Basic Protein; Polyradiculoneuropathy; Radioimmunoassay

The purpose of the work was to assess changes in the activity of cytotoxic lymphocates in patients with cerebral infarction. The material comprised 27 patients with the diagnosis of cerebral infarction and 18 controls. The authors analyzed the activity of cytotoxic lymphocytes, against the cerebral antigen-encephalitogenic peptide (EP). As target cells they used syngenic lymphocytes coated with EP and labelled with 51Cr, the activity of which released during reaction with supernatan is proportional to the amount of cells disrupted by cytotoxic lymphocytes. The reaction is specific for the encephalitogenic peptide. The activity of specific cytotoxic lymphocytes was in patients with cerebral infarction almost four times higher than in controls. The percentage activity was higher in "seriously affected patients" and two weeks after the onset of the disease. Then the activity declined. Investigation of the activity of cytotoxic lymphocytes could prove important in patients with cerebral infarction with symptoms of sensitization against cerebral antigen.

Topics: Adult; Cerebral Infarction; Cytotoxicity, Immunologic; Female; Humans; Male; Middle Aged; Myelin Basic Protein; T-Lymphocytes, Cytotoxic

Topics: Aged; Astrocytes; Biomarkers; Cerebral Infarction; Glial Fibrillary Acidic Protein; Histiocytes; Humans; Immunohistochemistry; Middle Aged; Myelin Basic Protein

Topics: Adult; Cerebral Infarction; Concanavalin A; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Myelin Basic Protein; Phytohemagglutinins