myelin-basic-protein and Spinal-Cord-Diseases

Methotrexate and cytarabine arabinoside are frequently administered intrathecally in the prophylaxis and treatment of patients with hematological malignancies. Myelopathy as a complication of intrathecal (IT) chemotherapy is rare in adults, with most of the cases described in the literature occurring in the pediatric population. Between January 2010 and March 2014, 587 newly diagnosed B cell acute lymphoblastic leukemia and 24 chronic myeloid leukemia lymphoid blast phase patients were seen at The University of Texas MD Anderson Cancer Center. This case series discusses seven adult cases deemed to have IT chemotherapy-induced myelopathy between 2010 and 2014 at MD Anderson Cancer Center. Five out of the seven patients had T2 abnormalities involving the dorsal columns of the spinal cord. An elevated myelin basic protein level was noted in the two patients in whom it was checked. The wide range of dosage and timing with respect to IT chemotherapy administration suggests an idiosyncratic reaction or individual threshold to the development of myelopathy. By describing the largest case series of myelopathy in adults, we aim to raise awareness about this rare albeit devastating complication. Based on the seven cases described we would recommend-MRI of the spine with T2-weighted imaging in the sagittal and axial planes in leukemia patients with unexplained myelopathy and consideration to delay IT chemotherapy until after an extensive work-up to rule out CNS leukemia. Though more data are needed on the use of folate metabolites, preliminary results have shown some promise in the treatment of methotrexate-induced myelopathy and may be a potential consideration for future patients suspected to have chemotherapy induced myelopathy.

Topics: Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Cytarabine; Female; Humans; Injections, Spinal; Leukemia, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Magnetic Resonance Imaging; Male; Methotrexate; Middle Aged; Myelin Basic Protein; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Spinal Cord; Spinal Cord Diseases

Exposure to environmental toxins increases the risk of neurodegenerative diseases including Parkinson's disease (PD). Rotenone is a neurotoxin that has been used to induce experimental Parkinsonism in rats. We used the rotenone model of experimental Parkinsonism to explore a novel aspect of extra-nigral degeneration, the neurodegeneration of spinal cord (SC), in PD. Rotenone administration to male Lewis rats caused significant neuronal cell death in cervical and lumbar SC as compared with control animals. Dying neurons were motoneurons as identified by double immunofluorescent labeling for terminal deoxynucleotidyl transferase, recombinant-mediated dUTP nick-end labeling-positive (TUNEL(+)) cells and choline acetyltransferase (ChAT)-immunoreactivity. Neuronal death was accompanied by abundant astrogliosis and microgliosis as evidenced from glial fibrillary acidic protein (GFAP)-immunoreactivity and OX-42-immunoreactivity, respectively, implicating an inflammatory component during neurodegeneration in SC. However, the integrity of the white matter in SC was not affected by rotenone administration as evidenced from the non co-localization of any TUNEL(+) cells with GFAP-immunoreactivity and myelin basic protein (MBP)-immunoreactivity, the selective markers for astrocytes and oligodendrocytes, respectively. Increased activities of 76 kD active m-calpain and 17/19 kD active caspase-3 further demonstrated involvement of these enzymes in cell death in SC. The finding of ChAT(+) cell death also suggested degeneration of SC motoneurons in rotenone-induced experimental Parkinsonism. Thus, this is the first report of its kind in which the selective vulnerability of a putative parkinsonian target outside of nigrostriatal system has been tested using an environmental toxin to understand the pathophysiology of PD. Moreover, rotenone-induced degeneration of SC motoneuron in this model of experimental Parkinsonism progressed with upregulation of calpain and caspase-3.

Topics: Animals; Calpain; Caspase 3; CD11b Antigen; Choline O-Acetyltransferase; Enzyme Activation; Glial Fibrillary Acidic Protein; In Situ Nick-End Labeling; Male; Motor Neurons; Myelin Basic Protein; Nerve Degeneration; Phosphopyruvate Hydratase; Rats; Rats, Inbred Lew; Rotenone; Spinal Cord Diseases; Time Factors; Tyrosine 3-Monooxygenase

Emerging evidence suggests that cell-based remyelination strategies may be a feasible therapeutic approach for CNS diseases characterized by myelin deficiency as a result of trauma, congenital anomalies, or diseases. Although experimental demyelination models targeted at the transient elimination of oligodendrocytes have suggested that transplantation-based remyelination can partially restore axonal molecular structure and function, it is not clear whether such therapeutic approaches can be used to achieve functional remyelination in models associated with long-term, irreversible myelin deficiency. In this study, we transplanted adult neural precursor cells (aNPCs) from the brain of adult transgenic mice into the spinal cords of adult Shiverer (shi/shi) mice, which lack compact CNS myelin. Six weeks after transplantation, the transplanted aNPCs expressed oligodendrocyte markers, including MBP, migrated extensively along the white matter tracts of the spinal cord, and formed compact myelin. Conventional and three-dimensional confocal and electron microscopy revealed axonal ensheathment, establishment of paranodal junctional complexes leading to de novo formation of nodes of Ranvier, and partial reconstruction of the juxtaparanodal and paranodal molecular regions of axons based on Kv1.2 and Caspr (contactin-associated protein) expression by the transplanted aNPCs. Electrophysiological recordings revealed improved axonal conduction along the transplanted segments of spinal cords. We conclude that myelination of congenitally dysmyelinated adult CNS axons by grafted aNPCs results in the formation of compact myelin, reconstruction of nodes of Ranvier, and enhanced axonal conduction. These data suggest the therapeutic potential of aNPCs to promote functionally significant myelination in CNS disorders characterized by longstanding myelin deficiency.

Topics: Animals; Axons; Cell Differentiation; Demyelinating Diseases; Disease Models, Animal; Evoked Potentials; Mice; Mice, Mutant Strains; Myelin Basic Protein; Nerve Fibers, Myelinated; Neural Conduction; Neuroglia; Neurons; Ranvier's Nodes; Spinal Cord Diseases; Stem Cell Transplantation

Analysis of cerebrospinal fluid (CSF) is part of a routine clinical workup in veterinary patients when neurologic disease is suspected. However, knowledge of particular protein markers of disease in CSF is limited. The concentration of myelin basic protein (MBP) in CSF is used as a biochemical marker in humans to evaluate demyelinating lesions in the central nervous system (CNS).. The purpose of this study was to evaluate an ELISA for determination of MBP concentration in the CSF of German shepherd dogs with degenerative myelopathy (GSDM).. Cross-reactivity of the anti-human polyclonal antibody used in a commercial ELISA (Active MBP ELISA, Diagnostic Systems Laboratories Inc, Webster, TX, USA) was tested with canine MBP by immunoblotting. CSF samples were collected from both the cisterna magna and the lumbar cistern of 8 clinically healthy control dogs and 8 German shepherd dogs clinically diagnosed with GSDM. MBP concentrations were measured in all CSF samples using the ELISA.. The mean MBP concentration in CSF from the lumbar cistern of dogs with GSDM (3.13 -/+ 0.46 ng/mL) was significantly higher than that in the cisterna magna (0.70 -/+ 0.06 ng/mL) and from both cisternal (0.47 -/+ 0.07 ng/mL) and lumbar (0.94 -/+ 0.37 ng/mL) samples from control dogs.. The MBP ELISA has potential as a supplemental test of CSF to diagnose demyelinating disorders in dogs.

Topics: Animals; Biomarkers; Dog Diseases; Dogs; Myelin Basic Protein; Spinal Cord Diseases

Remyelination is a critical step for recovery of function after demyelination and defines the ability to generate new myelin. This repair process is dependent on the presence of resident oligodendrocyte progenitors (OLPs) that have been shown to remyelinate axons after demyelination. We have previously shown that the levels of the cell cycle inhibitor p27Kip-1 modulate the number of neonatal cortical OLPs. We now asked whether this cell cycle molecule plays also a role in regulating the number of adult OLP in the spinal cord after demyelination induced by lysolecithin injection. The proliferative response of OLP in the spinal cord of injected wild-type (wt) and p27Kip-1 null mice was evaluated 3 days after lesion. In vivo labeling with bromodeoxyuridine (BrdU) was used to identify cells in S phase. Double immunofluorescence for the OLP marker NG2, and for BrdU was used to count the number of proliferating progenitors. Consistent with a role of p27Kip-1 in regulating the number of adult OLP in the injured spinal cord, a larger number of proliferating OLPs was observed in p27Kip-1null mice compared with wild-type controls. These cells were able to differentiate as assessed by the presence of MBP+ cells in the spinal cord 14 days after injury. We conclude that the cellular levels of the cell cycle inhibitor p27Kip-1 modulate the repair response of OLPs to injury in the adult spinal cord.

Topics: Animals; Bromodeoxyuridine; Cell Count; Cell Cycle Proteins; Cell Differentiation; Cell Division; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p27; Demyelinating Diseases; Female; Gene Expression Regulation; Lysophosphatidylcholines; Male; Mice; Mice, Knockout; Myelin Basic Protein; Nerve Regeneration; Oligodendroglia; S Phase; Spinal Cord Diseases; Stem Cells; Tumor Suppressor Proteins

Poly(ADP-ribose) polymerase (PARP) activity has been implicated in the pathogenesis of several central nervous system (CNS) disorders. For example, the presence of extensive poly(ADP)ribosylation in CNS tissues from animals with experimental allergic encephalomyelitis (EAE) indicates that PARP activity may be involved in this inflammatory disease process. Using PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl], a selective PARP inhibitor, we studied the mechanisms through which PARP activity may contribute to the onset of acute EAE. PLSJL mice immunized with myelin antigens were treated with PJ34, and the effects on the progression of EAE and several other parameters relevant to the disease process were assessed. PJ34 exerted therapeutic effects at the onset of EAE that were associated with reduced CNS inflammation and the maintenance of neurovascular integrity. Expression of genes encoding the intercellular adhesion molecule-1 (ICAM-1) and the inflammatory mediators interferon-gamma, tumor necrosis factor-alpha, and inducible nitric-oxide synthase were decreased in CNS tissues from drug-treated animals. Administration of PJ34 biased the class of myelin basic protein (MBP)-specific antibodies elicited from IgG2a to IgG1 and IgG2b and modulated antigen-specific T-cell reactivity. Therefore, the mode of action of PJ34 at the onset of EAE is likely mediated by a shift in the MBP-specific immune response from a proinflammatory Th1 toward an anti-inflammatory Th2 phenotype.

Topics: Adjuvants, Immunologic; Animals; Blood-Brain Barrier; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Intercellular Adhesion Molecule-1; Mice; Myelin Basic Protein; Phenanthrenes; Poly(ADP-ribose) Polymerase Inhibitors; Spinal Cord Diseases; T-Lymphocytes; Th2 Cells; Tumor Necrosis Factor-alpha

The extracellular signal-regulated kinases (ERK) participate in numerous signaling pathways and are abundantly expressed in the CNS. It has been proposed that ERK activation promotes survival in models of neuronal injury. Inhibition of MEK, the upstream kinase that activates ERK, however, leads to neuroprotection in models of cerebral ischemia and trauma, suggesting that in this context ERK activation contributes to cellular damage. The effect of ischemia and reperfusion on activity and expression of ERK was investigated using a reversible model of rabbit spinal cord ischemia. Active ERK was observed in nai;ve animals, which decreased during 15 to 60 min of ischemia. Upon reperfusion, a robust activation of ERK was observed in animals occluded for 60 min that remained permanently paraplegic. Immunohistochemical analyses revealed increased staining of phosphorylated ERK (pERK) in glial cells and faint nuclear staining in motor neurons of animals occluded for 60 min and reperfused for 18 h. In contrast ERK activity did not increase in animals occluded for 15 min that regained motor function. No evidence of increased pERK immunoreactivity in motor neurons or nuclear translocation was noted in these animals. ERK1 was demonstrated to be identical to a p46 c-Jun/ATF-2 kinase previously shown to be activated by reperfusion after a 60-min occlusion. The results suggest that activation of ERK during reperfusion of ischemic spinal cord participates in the cellular pathways leading to neuronal damage.

Topics: Activating Transcription Factor 2; Animals; Cell Line; Cyclic AMP Response Element-Binding Protein; Enzyme Activation; Hippocampus; Immunoblotting; Immunohistochemistry; Ischemia; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Myelin Basic Protein; Phosphorylation; Precipitin Tests; Protein Kinases; Rabbits; Reperfusion; Spinal Cord Diseases; Subcellular Fractions; Time Factors; Transcription Factors

Vacuolar myelopathy (VM) is a frequent central nervous system complication of human immunodeficiency virus type 1 (HIV-1) infection. We report here that transgenic (Tg) mice expressing even low levels of Nef in oligodendrocytes under the regulation of the myelin basic protein (MBP) promoter (MBP/HIV(Nef)) developed VM similar to the human disease in its appearance and topography. The spinal cords of these Tg mice showed lower levels of the myelin proteins MAG and CNPase and of the 21-kDa isoform of MBP prior to the development of vacuoles. In addition, Tg oligodendrocytes in primary in vitro cultures appeared morphologically more mature but, paradoxically, exhibited a less mature phenotype based on O4, O1, CNPase, and MBP staining. In particular, mature CNPase(+) MBP(+) Tg oligodendrocytes were less numerous than non-Tg oligodendrocytes. Therefore, Nef appears to affect the proper differentiation of oligodendrocytes. These data suggest that even low levels of Nef expression in human oligodendrocytes may be responsible for the development of VM in HIV-1-infected individuals.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Cell Differentiation; Cells, Cultured; Gene Products, nef; Humans; Immunohistochemistry; Mice; Mice, Transgenic; Myelin Basic Protein; Myelin-Associated Glycoprotein; Oligodendroglia; Phenotype; Spinal Cord; Spinal Cord Diseases; Transgenes; Vacuoles

Alterations of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) and leakage of serum proteins induce vasogenic edema and cell damage. The possibility that two members of the neurotrophin family, BDNF or IGF-1 induce neuroprotection by attenuating the BSCB permeability following trauma was examined in a rat model. Repeated topical application of BDNF or IGF-1 (0.1 1microg, 0.5 microg or 1 microg in 10 microl) onto the spinal cord 30 min before SCI or 2, 5, 10 or 30 min thereafter significantly attenuated BSCB permeability to Evans blue and iodine. In the neurotrophin treated rats. edema formation, degradation of MBP, and myelin vesiculation were much less frequent compared to the untreated traumatised rats. The protective effect of BDNF and IGF-1 was most pronounced at the high dose (1 microg in 10 microl) given either 30 min before or within 10 min after SCI. The observations suggest that early intervention with neurotrophins in high doses following trauma (within 10 min) attenuates disturbances of the fluid microenvironment of the spinal cord. This indicates that BSCB opening plays an important role in SCI induced myelin vesiculation and cord pathology.

Topics: Animals; Axons; Brain-Derived Neurotrophic Factor; Capillary Permeability; Diffuse Axonal Injury; Edema; Endothelium, Vascular; Insulin-Like Growth Factor I; Male; Microcirculation; Myelin Basic Protein; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Diseases; Spinal Cord Injuries

Inflammation of multiple sclerosis (MS) brain and spinal cord tissue consists of macrophages, T lymphocytes and cytokines as well as B lymphocytes and immunoglobulins (IgGs). IgG can be detected in high concentrations in both central nervous system tissue and cerebrospinal fluid (CSF). Using a sensitive radioimmunoassay (RIA), autoantibodies to myelin basic protein (anti-MBP) can be detected in the CSF of 90-95% of MS patients with active disease. The purpose of the present report was to determine whether these same autoantibodies can be reliably detected in non-MS patients. Between 1978 and 1998, CSF was collected from 1,968 control non-MS patients with psychiatric, inflammatory and noninflammatory neurological diseases as well as nonneurological systemic diseases, and anti-MBP were measured by the same RIA used to detect anti-MBP in MS CSF. Anti-MBP were undetectable in 98% of CSF samples from non-MS controls. In the remaining 2% of control samples, CSF IgGs capable of binding to MBP in vitro were unpredictably detected. This latter group included 1% of patients with miscellaneous diseases such as encephalomyelitis, 5 siblings with familial spastic paraparesis, rare patients with strokes, Wernicke-Korsakoff's syndrome, inherited leukodystrophy, motor neuron disease and some patients with miscellaneous spinal cord diseases. An additional 1% of patients included a group with neurological symptoms suggestive of early or predisseminated MS. The high prevalence of free and/or bound anti-MBP in the CSF of MS patients and the rare and unpredictable occurrence in the CSF of non-MS patients suggest that autoimmunity to MBP may be operative in the demyelination of MS. Molecular clones of anti-MBP with specificity towards variable surface or cryptic MBP epitopes in vivo may determine whether or not they are involved in the demyelinating process, and this variability may also be present within the MS population. Potential mechanisms of anti-MBP-mediated demyelination in MS patients are discussed.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Central Nervous System Diseases; Cerebrovascular Disorders; Child; Encephalomyelitis; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Neurodegenerative Diseases; Sclerosis; Spinal Cord Diseases

Animals with spontaneous mutations affecting myelin formation have provided useful information about the genetic and cellular mechanisms regulating normal and abnormal myelination. In this paper we describe a novel murine mutation termed hindshaker (hsh), which is inherited in an autosomal recessive manner. Affected mice are characterised by a variable tremor of the hind end which commences at about 2 weeks of age and largely disappears in animals older than 6 weeks. There is hypomyelination affecting predominantly the spinal cord, although the optic nerves and brain are involved to a much lesser degree. The defect of thinly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. The myelin structure appears normal and immunostains for the major proteins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are fewer mature cells. The hsh mutation appears to delay the maturation of oligodendrocytes, particularly in the spinal cord. Additionally, there is a considerable variation in phenotypic expression and in penetrance when the mutation is expressed on different genetic backgrounds, suggesting the hsh locus is subject to the influence of modifying gene(s). Identification of the hsh gene should identify a factor important in the development of oligodendrocytes, particularly those in the spinal cord.

Topics: Animals; Autoradiography; Female; Glial Fibrillary Acidic Protein; Hindlimb; Immunohistochemistry; In Situ Hybridization; Male; Mice; Mice, Inbred C3H; Mice, Neurologic Mutants; Mutation; Myelin Basic Protein; Myelin Proteolipid Protein; Myelin Sheath; Phenotype; RNA, Messenger; Spinal Cord; Spinal Cord Diseases; Tremor

Vacuolar myelopathy is a common neurological complication in AIDS patients. The pathogenesis of this spinal cord white matter disease remains unclear and it is still debated whether infection of spinal cord with the human immunodeficiency virus type 1 (HIV-1) is causing the disease. We have generated transgenic mice expressing the entire HIV-1 genome under the regulation of an oligodendrocyte-specific promoter. These mice develop spinal cord vacuolar lesions similar to those found in AIDS patients. This animal model provides in vivo evidence linking the expression of HIV-1 proteins in oligodendrocytes to the spinal cord damage found in vacuolar myelopathy.

Topics: Acquired Immunodeficiency Syndrome; Animals; Central Nervous System; Gene Expression Regulation, Viral; HIV-1; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myelin Basic Protein; Oligodendroglia; Paralysis; Spinal Cord; Spinal Cord Diseases; Tissue Distribution; Vacuoles; Viral Proteins

A 9-year-old girl had hemiparesis, and a diagnosis of primary Sjögren syndrome was made. The neurologic dysfunction was multifocal, involving both the brain and spinal cord, and was recurrent; the findings mimicked multiple sclerosis. Corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial.

Topics: Brain; Child; Diagnosis, Differential; Encephalomyelitis; Female; Hemiplegia; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Multiple Sclerosis; Myelin Basic Protein; Prednisolone; Sjogren's Syndrome; Spinal Cord Diseases; Tomography, X-Ray Computed

Recently, glial cytoplasmic inclusion (GCI) has been demonstrated to be argyrophilic cytoplasmic body by silver staining in the oligodendroglia of patients with multiple system atrophy. We observed such GCIs in all 20 cases of multiple system atrophy. No GCI was noticed in all 6 cases of hereditary spinocerebellar degenerations. Immunohistochemically, GCI was stained positively with antibodies to ubiquitin, alpha-tubulin, and beta-tubulin, of which characteristics is consistent with previous reports. In addition, GCI was first demonstrated to react with an antibody to microtubule-associated protein-1B(5), which is one of the proteins of cytoskeleton organization and a component of cross-bridges between microtubular assembly. The result suggests strong relationship between the formation of the OCI and immunohistochemical expression of MAP-1B(5).

Topics: Antibodies, Monoclonal; Cells, Cultured; Cerebellar Ataxia; Humans; Immunohistochemistry; Inclusion Bodies; Microtubule Proteins; Myelin Basic Protein; Neuromuscular Diseases; Oligodendroglia; Silver Staining; Spinal Cord Diseases

One characteristic of experimental allergic encephalomyelitis (EAE) in all species is the presence of a considerable leukocyte infiltrate in the central nervous system (CNS). By adoptive transfer of EAE into irradiated or nonirradiated Lewis strain rats we now show that the bulk (greater than 90%) of infiltrating cells in the CNS are superfluous to the induction of disease, as lethally irradiated recipients, despite having very few infiltrating cells in the CNS, acquire severe paralytic EAE. The reduction in the level of infiltration in irradiated recipients is selective, however, as both irradiated and nonirradiated diseased animals have very similar numbers of cells expressing IL-2-R. Disease in irradiated recipient animals is associated with substantial submeningeal hemorrhage in the spinal cord and brain stem and similar hemorrhages are found in recipients rendered leukopenic with cytotoxic drugs. Clinical signs of disease and hemorrhage are preventable, however, by administration to the recipient rats of mAbs specific for the CD4 antigen. Classic delayed-type hypersensitivity (DTH) reactions are transferable with the same cells that produce EAE in both irradiated and nonirradiated recipient rats, but such transfer of DTH is observed only in nonirradiated recipient animals and not in irradiated rats. Collectively, the findings reported herein support the conclusion that the paralysis characteristic of acute EAE is mediated by the direct action of very small numbers of activated CD4+ lymphocytes that infiltrate the CNS and produce their effects by inducing vascular damage. The findings are not consistent with reports that the lesions in EAE are produced by a classic DTH reaction.

Topics: Animals; Busulfan; Cells, Cultured; Central Nervous System; Cerebral Hemorrhage; Chlorambucil; Encephalomyelitis, Autoimmune, Experimental; Female; Hemorrhage; Hypersensitivity, Delayed; Immunization, Passive; Leukopenia; Male; Myelin Basic Protein; Ovalbumin; Rats; Rats, Inbred Lew; Receptors, Immunologic; Receptors, Interleukin-2; Spinal Cord Diseases; Spleen; T-Lymphocytes, Helper-Inducer; Whole-Body Irradiation

The neurological signs induced by injection of tunicamycin are, in young adult rats, virtually identical to those typical of acute experimental autoimmune encephalomyelitis (EAE). Vasogenic exudation, of which the occurrence in the spinal cord of EAE rats has been shown to coincide with the onset of clinical signs, was investigated by quantitative electroimmunoblotting of central nervous system (CNS) tissue at various times following tunicamycin injection of young adult rats. Highly elevated levels of extravasated plasma proteins were observed in the spinal cord from 48 h after injection and, as in EAE rats, these increases coincided with the onset of neurological impairment. At 72 h post-injection, significant increases were also found in the brain of affected animals, albeit at much reduced levels. This is in contrast to previously reported findings in nursling rats where oedema was shown to be predominantly located in the brain. Quantitative electroimmunoblotting for myelin basic protein (MBP) in the CNS of tunicamycin-treated young adult rats indicated that, as in acute EAE, no extensive demyelination had occurred. These data provided further evidence that in both neurological diseases, vasogenic oedema of the spinal cord may be causally related to the appearance of neurological signs and suggested that its differential localization in the CNS may lead to differential neurological impairment.

Topics: Animals; Brain Chemistry; Edema; Encephalomyelitis, Autoimmune, Experimental; Immunoglobulin G; Myelin Basic Protein; Nerve Tissue Proteins; Rats; Serum Albumin; Spinal Cord; Spinal Cord Diseases; Tunicamycin

A 30-year-old homosexual man presented with widespread Burkitt's lymphoma. On the basis of immunologic and viral studies, he was suspected of having the acquired immune deficiency syndrome. Following chemotherapy that included intrathecal cytosine arabinoside and methotrexate, brain stem edema, paraplegia, and an elevated cerebrospinal fluid level of myelin basic protein developed. Autopsy revealed vacuolar demyelination of spinal cord, brain stem, and cerebellum. The pathologic findings were similar to those reported to occur in myelopathy associated with intrathecal chemotherapy, but far more extensive. The contribution of the suspected acquired immune deficiency syndrome is unknown.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Brain Stem; Burkitt Lymphoma; Cerebellum; Demyelinating Diseases; Homosexuality; Humans; Injections, Spinal; Male; Myelin Basic Protein; Spinal Cord Diseases

Patients admitted to the neurosurgical wards for the management of nervous system tumours, subarachnoid and intracerebral haemorrhage, head injury, spinal and peripheral nerve lesions, and other miscellaneous neurosurgical conditions, were studied by assay of serum immunoreactivity for myelin basic protein. Of 171 patients, 70% proved to have elevated myelin basic protein activity. In cerebral cases the extent of brain damage assessed by clinical methods appeared to correlate with the appearance of elevated serum myelin basic protein. In spinal and peripheral nerve cases no similar elevation of myelin basic protein was observed.

Topics: Adolescent; Adult; Brain Diseases; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Myelin Basic Protein; Nervous System Diseases; Peripheral Nervous System Diseases; Postoperative Complications; Prognosis; Radioimmunoassay; Spinal Cord Diseases

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

Topics: Adult; Female; Humans; Lupus Erythematosus, Systemic; Myelin Basic Protein; Spinal Cord Diseases

Topics: Cerebrovascular Disorders; Humans; Myelin Basic Protein; Radioimmunoassay; Spinal Cord Diseases

Topics: Animals; Cattle; Cerebrovascular Disorders; Humans; Multiple Sclerosis; Myelin Basic Protein; Nervous System Diseases; Radioimmunoassay; Spinal Cord Diseases

Topics: Animals; Autolysis; Brain; Brain Edema; Central Nervous System; Demyelinating Diseases; Edema; Female; Lipid Metabolism; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Rats; Spinal Cord; Spinal Cord Diseases; Time Factors; Triethyltin Compounds