Ganglioside complexes as new target antigens in Guillain-Barré syndrome

Antibodies specific for a complex of gangliosides GD1a and GD1b (GD1a/GD1b) were found in sera from eight of 100 patients with Guillain-Barre syndrome (GBS) by the use of enzyme-linked immunosorbent assay and thin-layer chromatogram immunostaining. Those sera also had antibody activities to such ganglioside complexes as GD1a/GM1, GD1b/GT1b, and GM1/GT1b but had little or no reactivity to the each isolated antigen. Clustered epitopes of the ganglioside complex in the plasma membrane may be targeted by such an antibody, and interaction between the antibody and ganglioside complex may induce the neuropathy.     

Propagation of tonic posturing in supplementary motor area (SMA) seizures

We analyzed ictal motor symptoms in 10 patients diagnosed to have supplementary motor area (SMA) seizures based on ictal encephalographic (EEG) findings and ictal clinical semiology. Inclusion criteria were (1) EEG seizure pattern in the vertex for the scalp recording or in the area over and/or adjacent to SMA for epicortical recording and (2) ictal motor semiology characterized, as previously reported, by sudden and a brief tonic posturing of extremities and trunk mainly occurring during sleep without loss of consciousness. In 50% (5/10) of the patients, tonic posturing began in one part of the body and moved to other part(s) in 5-10s. Unlike Jacksonian march seen in seizures involving the primary sensorimotor area (S1-M1), it spread in no accordance with the somatotopy in S1-M1. The sequential propagation of tonic posturing may represent the somatotopic organization within the SMA proper.     

Plasminogen activator inhibitor-1 aids survival of neurites on neurons derived from pheochromocytoma (PC-12) cells

Plasminogen activator inhibitor-1 is a serpin that regulates the activities of plasminogen activators. However, its physiological roles in the CNS are incompletely understood. We have found that plasminogen activator inhibitor-1 has a novel biological function in the CNS: the contribution to survival of neurites on neurons. PC-12 cells treated with nerve growth factor differentiated into neurons and formed a network of neurites. In a serum-free culture medium, these neurites disappeared within 24 h. The addition of plasminogen activator inhibitor-1 prevented the disintegration of the neuronal networks, while the addition of the serpin inhibitors aprotinin and antipain did not. The plasminogen activator inhibitor-1 maintained or promoted the phosphorylated state of extracellular signal-regulated kinase (ERK), but not of protein kinase B (Akt). These results are the first evidence that plasminogen activator inhibitor-1 in the CNS acts to maintain the morphology of neurites via activation of the ERK-related pathway in the neurons.     

Oxidative stress and microglial activation in substantia nigra following striatal MPP+

The present study aims to study sequential alterations occurring in both dopaminergic neurons and microglia in substantia nigra (SN) following intrastriatal injection of 1-methyl-4-phenylpridium ion (MPP+) in rats. Heme oxygenase-1 (HO-1), a marker of oxidative stress, first appeared in dopaminergic neurons in SN at 1 day post-lesion. Subsequently, microglia in SN exhibited morphological changes indicative of activation. At 7 days post-lesion, those findings increased severity and 7a significant reduction in the number of dopaminergic neurons was observed. The present finding suggests that extensive oxidative stress and secondary-induced neuroinflammation play a relevant role in MPP(+)-induced retrograde dopaminergic neuron degeneration. We hope that this model will be useful in developing a disease modifying therapy of Parkinson's disease.     

Experimental diabetes accelerates accumulation of fluorescent pigments in rat trigeminal neurons

The purpose of this study was to investigate autofluorescent pigment granules (lipofuscin, ceroid) in the trigeminal neurons (TN) during aging and streptozotocin-induced diabetes. Four young adult male rats were injected with streptozotocin (STZ; 50 mg/kg) to produce diabetes (DM), for comparison with four young uninjected control rats and four aged rats (90 weeks old). Eight weeks after STZ injection, all rats were fixed with 4% paraformaldehyde, and paraffin sections of TN were prepared and observed by fluorescence microscopy. We found the number of neurons with autofluorescent pigments had increased to 30.38% of the total in DM compared to 8.98% in the control group, and 25.36% in the aged rats. The area of autofluorescence within those neurons was 16.84% in aged rats, 13.02% in DM and 4.45% in the controls. Thus, DM caused accelerated accumulation of fluorescent granules in trigeminal neurons, and this change may show that premature aging contributes to neuronal functional decline and morphological change.     

Case of dentatorubral-pallidoluysian atrophy with onset of psychomotor retardation in infancy

We report a patient with dentatorubral-pallidoluysian atrophy (DRPLA). She developed normally until the age of 6 month, when she could sit by herself. However, her psychomotor development was subsequently slow with gradual appearance of equilibrium disturbances and involuntary movements such as polymyoclonia and chorea. Her development deteriorated after myoclonic seizures developed at 4.5 years of age. Electroencephalograms showed semi-continuous bursts of diffuse irregular spike-wave complexes and MRI of the brain showed atrophy of the cerebellum and brainstem, and high signal intensities in the posterior periventricular triangle portion on T2-weighted images. Gene analysis performed at the age of 6 years revealed an expanded CAG repeat (17/74) at the DRPLA locus. The CAG repeat size was larger in this case than in cases of the adult and juvenile types with later onset, suggesting a correlation between repeat length and age at onset. Genetic examination of the family members was not performed because of her mother's fear and emotional confusion.     

Protective effect of (+)-catechin against 5-fluorouracil-induced myelosuppression in mice

The object of this study was to investigate the efficacy of (+)-catechin, which was isolated from Actinidia arguta Planch (Actinidiaceae), as a bone marrow cell proliferation-promoting compound against the hematotoxicity of 5-fluorouracil (5-FU) in mice. Intraperitoneally injected (+)-catechin (1 and 10 mg/kg per day) accelerated the recovery of the number of white blood cells (WBC) and platelets (PLT) but did not affect the number of circulating red blood cells (RBC). (+)-Catechin also augmented the number of myelocytes and splenocytes. Dual color flow cytometric analysis revealed that (+)-catechin reversed the reduction of the population of leukocytes (CD11b+ monocytes, Gr-1+ granulocytes and CD3+ T and CD45RA+ B lymphocytes) in whole blood, spleen and bone marrow caused by 5-FU. (+)-Catechin (1 and 10 mg/kg per day) showed remarkable recovery of Gr-1+ cells in all three types of tissues and of CD11b+ cells in the bone marrow cells. These findings suggest that (+)-catechin selectively enhances the recovery of the population of granulocytes reduced by 5-FU in mice.