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Central nervous system (CNS) inflammation causes severe neurological dysfunction, such as motor, sensory, and cognitive impairments. One of the reasons for the developing disease depends on the damage of neuronal network, a predominant feature of many CNS diseases. Therefore, protection and/or regeneration of damaged neuronal network after injury is considered to be useful for treating neurological diseases; however, the mechanism of protection and regeneration of neuronal network is not fully elucidated. In this paper, I describe our recent findings about the mechanism that disrupt and regenerate neuronal network by using animal model of multiple sclerosis. I also introduce the key molecules which is involved in inflammation, neurovascular interaction, and systemic regulation. These findings have a potential to contribute develop the new therapies for treating neurological disease.

Many tick-borne flaviviruses causes fatal encephalitis in humans and animals with severe sequelae. However, it remains unclear how viral replication and pathogenicity contribute to the neurologic manifestations. In this paper, I summarized the specific replication mechanism of tick-borne flaviviruses in neurons and their effect on the pathogenicity of neurological disease. Our findings of the unique virus-host interaction in central nerve system will improve further understanding of the molecular mechanisms of viral replication and the pathogenicity of neurotropic viruses.

Bone tissues including bone marrow are comprised of various cells. A growing body of evidence suggests that nerve cells which exist in and around bone such as periosteal and bone marrow build a close relationship with bone cells. Namely, it was revealed that central nervous system governs bone tissues via peripheral nervous system and neurotransmitters or cytokines play a role for the communication between bone and nerve in the last decade. In this paper, I would like to review "osteo-neural" related factors which has been well-documented so far.

It is well-known that the central nervous system is thoroughly resistant to ionizing radiation as high-dose radiation exposure is required for causing neuronal death. In contrast, recent studies have revealed that the hippocampus, which could be the main organ involved in disorder of higher brain functions after radiation therapy, contains radiation-sensitive cell fractions. In this paper, the basics of radiation effects and the molecular mechanism of neurotoxicity of radiation have been reviewed and discussed.

Immunoglobulin G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4-RD can occur in various organs, including the pancreas, lacrimal gland, salivary gland, thyroid, lung, bile duct, liver, gastrointestinal tract, kidney, prostate, retroperitoneum, arteries, lymph nodes, skin, and breast. Steroid therapy is often effective. In the field of neurology, pachymeningitis (IgG4-related pachymeningitis) and hypophysitis (IgG4-related hypophysitis) are known to be related to IgG4-RD. Recently, a few papers have described the involvement of peripheral nerves in IgG4-RD. Here, we describe the concept of IgG4-RD and highlight the involvement of the central and peripheral nervous systems in IgG4-RD.

Neurotoxicity of organic solvents is one of the most important emerging issues in the field of occupational health. Psychological testing has been proven useful not only in clinical diagnosis but also in experimental and epidemiological studies. Although various psychobehavioral performance test batteries have been applied in the study of neurotoxicity of organic solvents during these last two decades among European countries and America, only few studies have been made on these in Japan. It is therefore considered very important to review the major papers published to date, clarify the issues being currently discussed, and propose important studies for future. The present paper provides a review of the results obtained by the application of behavioral performance tests in the study of solvent toxicity. The studies reviewed are classified into the following five parts: 1. psychological test batteries developed to date, 2. human experimental studies and experimental field studies on the acute toxicity of organic solvents, 3. epidemiological studies on industrial workers, 4. characteristics of the central nervous system dysfunction caused by organic solvents, and 5. prognosis of workers diagnosed as chronic organic solvent intoxication. The paper also discusses the applicability of psychobehavioral techniques and addresses issues in data collection in the study of the effects of solvent exposure on the nervous system.

In a previous paper, we reported that PZ-177 had potent anti-inflammatory and analgesic activities. In the present work, acute toxicity and action of PZ-177 on the central nervous system were tested in comparison with PZ-222, one of metabolites of PZ-177, and mepirizole. Acute toxicity of PZ-177 was slightly less than that of aminopyrine and the same as that of mepirizole in mice and rats. PZ-177 produced from sedation to loss of righting reflex with the increase of dose. At a low dose with which the righting reflex was hot lost, PZ-177 decreased spontaneous locomotion of mice in the Animex test, produced muscle relaxation in rotarod and inclined screen tests, produced sleeping-pattern in electroencephalogram of rabbit, potentiated hypnosis of barbiturates and exerted an anti-convulsive effect in mice. In these depressive effects on the central nervous system, PZ-222 was very much lower and mepirizole slightly lower than PZ-177. It would thus appear that PZ-177 has more potent analgesic, antipyretic and anti-tussive actions than do PZ-222 and mepirizole.

Environmental factor is noteworthy for pathogenesis of ALS. Yase reported low contents of Ca, Mg and high contents of Al, Mn in environmental samples (soil and water) obtained from Kii Peninsula and Guam where ALS has been occurring in high incidence. In this paper, to evaluate the role of these environmental factors for degeneration of ALS, morphological, morphometrical and metal analytical studies on experimental animals will be described with special attention to the neurotoxicity of oral administration of Al. The rabbits (2-2.3 kg) were divided into 3 groups. Group 1 was fed standard diet (Ca 1.24% Mg 0.37%), Group 2 was fed low-Ca Mg diet (Ca 0.27% Mg 0.05%) for 40 days, and Group 3 was fed low-Ca Mg diet for 40 days and was injected Al-lactate solution (10 ml) into the stomach through the tube 6 times/week for 4 weeks. Al-lactate solution contained Al in dosage of 0.06 g/ml for the first 2 weeks and 0.12 g/ml for the following 2 weeks. And also to compare with the change by oral administration of Al, rabbits were injected Al-phosphate intracerebrally 14 days before the examination. The rabbits were anesthetized and perfused through the aorta with 10% formalin or 2.5% and 5% glutaraldehyde (pH 7.4), and examined light and electron microscopically. For morphometrical examination, 100 sections of 6 microns specimen at intervals of 30 microns in each rabbit spinal cord (c-5) were prepared and examined using the ocular micrometer. Contents of Al and Ca of the spinal cord and cortex were measured by neutron activation analysis with formalin fixed samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic manganese poisoning is characterized by mental and extrapyramidal disturbances. Parkinsonism-dementia complex (PD) on Guam is also manifested by progressive extrapyramidal syndrome and dementia. In PD, the reduced activities of catecholamine synthesizing enzymes in the brain has been demonstrated. On the other hand, the soil and water in Guam are rich in manganese, and one of the possible etiologic factors is trace element dysmetabolism in PD. The purpose of this paper is to clarify the effect of chronic manganese loading on the central nervous system. Manganese chloride (10 mg/ml of demineralized and distilled water) was administrated orally to Wistar female rats weighing 80-110 g. Six and 12 months after the administration, manganese loaded and control rats were sacrificed by perfusion for histological studies and by decapitation for the assay of tyrosine hydroxylase (TH) activity. The striatum, globus pallidus and substantia nigra were examined with electron microscopy. The brain for TH assay was dissected into four parts as the striatum, midbrain-thalamus, pons-medulla oblongata, and hypothalamus. Ultrastructural changes were overwhelmingly detected in the zona reticulata of the substantia nigra at 12 months. These changes were mainly composed of alterations of the postsynapse and neuronal soma--shrunken and electron dense dendrites accumulated degenerating materials and so-called simple atrophy of the neuron. Alterations in the presynapse were extremely milder than those in the postsynapse and neuron. At both 6 and 12 months, no significant changes in the striatum and globus pallidus were detected except for irregular windings of the plasma membrane in the axon terminal of the globus pallidus at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)