Oryeongsan (Goreisan) Ameliorates Experimental Autoimmune Encephalomyelitis.

Objective Oryeongsan (Goreisan), a formula composed of five herbal medicines, has long been used to treat impairments of the regulation of body fluid homeostasis. Goreisan has been revealed to have anti-inflammatory actions and inhibit a water channel, the aquaporin (AQP). We herein report the therapeutic effect of Goreisan on experimental autoimmune encephalomyelitis (EAE in, an animal model of inflammatory demyelinating diseases. Materials and Methods EAE mice immunized with MOG35-55 peptide were divided into Goreisan- and sham-treated groups. The clinical EAE score and histopathological finding of the central nervous system (CNS) were analyzed. For the proliferation assay, prepared spleen cells from immunized mice were cultured and analyzed for the [3H]-thymidine uptake and cytokine concentrations of the culture supernatant. The relative quantification of AQP4 mRNA in the CNS of EAE mice was analyzed quantitatively. Results The EAE score of the Goreisan-treated mice was significantly lower than that of the sham-treated mice. The CD4-positive cell number in the CNS of Goreisan-treated mice was lower than that of sham-treated mice. In the recall response to MOG35-55 peptide, the cell proliferation did not differ markedly between the spleen cells from Goreisan- and sham-treated mice. Furthermore, Goreisan decreased the mRNA level of AQP4 in the spinal cord during EAE. Conclusion Goreisan prevented the disease activity of EAE by inhibiting the migration of pathogenic cells into the CNS by suppressing the AQP4 expression in the CNS. Goreisan may have a therapeutic effect on inflammatory demyelinating diseases.

4-Aminopyridine ameliorates experimental autoimmune neuritis in Lewis rats.

We investigated the effect of 4-aminopyridine (4-AP) on experimental autoimmune neuritis (EAN) using a 4-AP-treated group in which 4-AP was administered in the diet, and a control group (n=10 per group). Electrophysiological and pathological assessment was performed in the sciatic nerve. The EAN clinical scores were significantly lower in the 4-AP-treated group than in the control group (p<0.05). The motor conductance velocity two weeks post-immunization was significantly higher in the 4-AP-treated group (p<0.05). Finally, 4-AP did not lead to pathological changes. Thus, 4-AP might be a potential therapeutic agent in demyelinating neuropathy.

Intravenous immunoglobulin preparation attenuates neurological signs in rat experimental autoimmune neuritis with the suppression of macrophage inflammatory protein -1α expression.

To clarify the mechanism of action of an intravenous immunoglobulin (IVIG) preparation in chronic inflammatory demyelinating polyneuropathy, the effects of IVIG were investigated using an experimental autoimmune neuropathy model in the rat. IVIG significantly suppressed the progression of neurologic signs and sciatic nerve conduction velocity with the inhibition of inflammatory cell infiltration, mainly of macrophages, to the peripheral nerves. A significant suppressive effect on the expression of macrophage inflammatory protein 1-α (MIP-1α) was simultaneously observed in the nerves. These results suggest that IVIG is effective for inflammatory demyelinating polyneuropathy by inhibiting the chemotactic factor of macrophages.

Guillain-Barré syndrome: update on immunobiology and treatment.

Growing experimental and clinical data have shed light on the pathophysiology of Guillain-Barré syndrome (GBS) and have further promoted the development of novel therapeutic strategies for the disorder. Elevated titer of antiganglioside antibodies is a characteristic of GBS. This may determine the clinical features of each case by binding to the sites where a target ganglioside antigen is localized. In experimental models of GBS and its variants, complementary inhibitory agents may exert neuroprotective efficacy by inhibiting antiganglioside antibody-mediated activation of the classical pathway. Complement-mediated disruption of the voltage-gated sodium channel cluster has been shown to be a principal cause of conduction failure in the model of acute motor axonal variants of GBS, protected by a complement inhibitor. Anti-GQ1b antibody-mediated injury at motor nerve terminals is also protected by complement inhibitors. In the future many kinds of drug candidates that inhibit activation of the complement system at various stages will be used in models of autoimmune neuropathy, in future applied to clinical trials for GBS and its variants. Complement-independent blockade of voltage-gated calcium channels or the apoptotic mechanism of neurons should also be considered. The pathogenic effect of antiganglioside antibody depends upon the local glycolipid environment in the nerve membrane as well as the antibody specificity.

Apoptosis of primary sensory neurons in GD1b-induced sensory ataxic neuropathy.

Experimental autoimmune sensory ataxic neuropathy was induced in three of six rabbits sensitized with GD1b ganglioside (GD1b-SAN). TUNEL assay was performed on sections of dorsal root ganglia in the cauda equina. The results showed the presence of TUNEL-positive neurons in all three rabbits affected with GD1b-SAN. In contrast, no such neurons were observed in any of the sections from the unaffected rabbits that had been inoculated with GD1b, rabbits inoculated with adjuvant alone or those without inoculation. These data support that an apoptotic mechanism is involved in the pathogenesis of GD1b-SAN.

Effects of phospholipids on antiganglioside antibody reactivity in GBS.

Serum antibody activities to mixtures of a ganglioside and various phospholipids were compared with those to a ganglioside alone in 30 anti-GM1 IgG-positive GBS patients and 30 anti-GQ1b IgG-positive Miller Fisher syndrome (MFS) patients. Anti-GM1-positive sera had higher antibody reactivities against a mixture of GM1 and several phospholipids including PA, PI and PS, than against GM1 alone. In contrast, in case of anti-GQ1b antibody, no phospholipid provided significant enhancement. Sphingomyelin provided decrease of the activity for both anti-GM1 and anti-GQ1b IgG. The effects of phospholipids must be considered to determine the pathogenetic role of antiganglioside antibodies in GBS and MFS.

[Diffusion-weighted magnetic resonance imaging findings at early stage of acute Wernicke encephalopathy].

We describe a patient with acute Wernicke encephalopathy (WE) in whom diffusion-weighted magnetic resonance imaging (DWI) were helpful for early diagnosis. A 66-year-old alcoholic man was admitted to our department because of recurrent mild drowsiness. Thiamine concentrations in blood were at the lower limit of normal. DWI demonstrated an abnormal signal intensity in the dorsal part of the midbrain, and high-dose thiamine therapy was started. These lesions disappeared on DWI after one month of follow-up, in association with clinical improvement. These findings suggest that DWI is useful for detecting WE at the early stage when high-dose thiamine treatment can improve the prognosis of WE.