myelin-basic-protein and Paraplegia

Previous studies have shown the existence of either cellular or humoral MBP-reactive elements up to 5 years after spinal cord injury (SCI), but not the presence of both after 10 years.. Twelve SCI patients, with more than 10 years of evolution, and 18 healthy blood donors were studied. Lymphocyte proliferation (colorimetric-BrdU ELISA assay) and antibody titers against MBP (ELISA Human IgG MBP-specific assay) were assessed.. SCI patients presented a significant T-cell proliferation against MBP (lymphocyte proliferation index: 3.7 ± 1.5, mean ± SD) compared to control individuals (0.7 ± 0.3; P < 0.001). Humoral response analysis yielded a significant difference (P < 0.0001) between the antibody titers of controls and SCI patients. A significant correlation between cellular and humoral responses was observed. Finally, patients with an ASIA B presented the highest immune responses.. This work demonstrates, for the first time, the existence of both cellular and humoral responses against MBP in the chronic stages (>10 years) of injury.

Topics: Adult; Antibodies; Case-Control Studies; Cell Proliferation; Chronic Disease; Female; Humans; Immunity, Humoral; Longitudinal Studies; Male; Middle Aged; Myelin Basic Protein; Paraplegia; Spinal Cord Injuries; T-Lymphocytes; Time Factors

The inherited disorders of CNS myelin formation represent a heterogeneous group of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2, and the gap junction protein alpha12 (GJA12) gene in a recessive form of PMD. The myelin basic protein (MBP) gene, which encodes the second most abundant CNS myelin protein after PLP1, presents rearrangements in hypomyelinating murine mutants and is always included in the minimal region deleted in 18q- patients with an abnormal hypomyelination pattern on cerebral MRI. In this study, we looked at the genomic copy number at the Golli-MBP locus in 195 patients with cerebral MRI suggesting a myelin defect, who do not have PLP1 mutation. Although preliminary results obtained by FISH suggested the duplication of Golli-MBP in 3 out of 10 patients, no abnormal gene quantification was found using Quantitative Multiplex PCR of Short Fluorescent fragments (QMPSF), Multiplex Amplifiable Probe Hybridization (MAPH), or another FISH protocol using directly-labelled probes. Pitfalls and interest in these different techniques to detect duplication events are emphasised. Finally, the study of this large cohort of patients suggests that Golli-MBP deletion or duplication is rarely involved in inherited defects of myelin formation.

Topics: DNA Primers; DNA Probes; Gene Dosage; Gene Duplication; Humans; In Situ Hybridization, Fluorescence; Magnetic Resonance Imaging; Membrane Proteins; Myelin Basic Protein; Myelin Proteolipid Protein; Nerve Tissue Proteins; Paraplegia; Pelizaeus-Merzbacher Disease; Polymerase Chain Reaction; Transcription Factors

Spinal cord injury results in a massive loss of neurons, and thus of function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell-based active vaccination is also neuroprotective. Immunization with myelin-associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBP-derived altered peptide ligands. Immunization with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization of nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury.

Topics: Adjuvants, Immunologic; Amino Acid Substitution; Animals; Autoantigens; Autoimmune Diseases; Contusions; Cordotomy; Exploratory Behavior; Female; Guinea Pigs; Immunotherapy, Active; Locomotion; Magnetic Resonance Imaging; Male; Myelin Basic Protein; Paraplegia; Peptide Fragments; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Safety; Single-Blind Method; Spinal Cord Injuries; Time Factors

Brain inflammation and paraplegia can be induced by an additional intraperitoneal (i.p.) and intracerebral (i.c.) restimulation in B6 mice after standard immunization with MBP in Freund's complete adjuvant (FCA) and Bordetella pertussis coadjuvant. Only the combination of i.p. MBP/FCA and i.c. MBP injection could induce clinical paraplegia; either one alone was not effective. Clinical symptoms would develop 2 days after the i.c. injection. The induction of paraplegia was MBP-specific, as irrelevant bovine serum albumin with the same protocol could not induce it. The i.p. restimulation was requisite and needed the MBP in FCA, as MBP in PBS was ineffective. Histopathological observation manifested cellular infiltration by leucocytes in perivascular spaces and cerebral cortex. Neutrophils were prominent at 12 h after i.c. injection, then were replaced by mononuclear cells 24 h later. There were dynamic changes in cell number and immunophenotype of VLA-4+ expression in cervical lymph node cells after i.c. injection. The cells derived from cervical lymph nodes had higher MBP-stimulated proliferation than that of distal lymph nodes. This additional i.p. and i.c. stimulation provides a new manipulation to study brain inflammation.

Topics: Animals; Bordetella pertussis; Brain; Cell Division; Cell Movement; Cells, Cultured; Cerebral Cortex; Encephalomyelitis, Autoimmune, Experimental; Flow Cytometry; Freund's Adjuvant; Immunization; Injections, Intraperitoneal; Injections, Intraventricular; Integrin alpha4beta1; Integrins; Leukocytes, Mononuclear; Lymph Nodes; Mice; Mice, Inbred Strains; Myelin Basic Protein; Neck; Neutrophils; Paraplegia; Receptors, Lymphocyte Homing; Serum Albumin, Bovine; T-Lymphocytes

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

Topics: Child; False Negative Reactions; Humans; Leukemia, Lymphoid; Methotrexate; Myelin Basic Protein; Paraplegia

An 11-year-old boy developed a severe myelopathy after an eight-year history of acute lymphoblastic leukemia and numerous courses of intrathecal chemotherapy. Myelin basic protein in the cerebrospinal fluid (CSF) was elevated. Neuropathologic examination disclosed extensive microvacuolar changes in the white matter of the spinal cord. The pathogenesis of myelopathy following intrathecal chemotherapy administered by lumbar puncture includes an early effect on the myelin sheath. Serial assessment of CSF myelin basic protein levels in patients receiving intrathecal chemotherapy may be useful in the early diagnosis of this disorder.

Topics: Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Humans; Injections, Spinal; Male; Methotrexate; Myelin Basic Protein; Paraplegia