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M Kumazaki

Publications and source records attributed to M Kumazaki.

31 records · Page 2Linked to original sources

Overshoot and high equilibrium in body temperature responses of rats to ambient heat: relation to thermoregulatory ability and improvement in estimation of survival time in a hot environment.

Physiological significance of body temperature responses to ambient heat (BTRAH) with high overshoot or a high equilibrium phase was studied in relation to thermoregulatory ability. Subsequently, an attempt was made to predict survival time (ST) by measuring the period required to attain a colonic temperature (Tco) of 42.0 degrees C (t42.0), whereas ST hitherto having been calculated on the basis of a period until Tco attains 42.5 degrees C (t42.5). Tco of rat was monitored continuously with a Cu-Co thermocouple during exposure to an ambient temperature (Ta) of 42.5 degrees C. The lower the overshoot temperature (Tos) or the equilibrium temperature (Teq), the longer the rats survived in a hot environment. The present findings further suggest that these two types of BTRAH are immature variations of the typical triphasic BTRAH which is characteristic of heat resistant individuals. A new regression line of ST (Y) as a function of the t42.0 (X) was obtained for most rats as follows: Y = 0.963X + 43.85 (male); and Y = 0.973X + 39.10 (female). This equation enabled to calculate ST without thermal death. However, the former approach based on t42.5 must be applied yet in small number of rats which showed the irregular BTRAHs with Tos or Teq higher than 42.0 degrees C. Delayed influence on survival and fecundity at a Ta of 24 degrees C were not found during one year following this hyperthermia up to 42.5 degrees C.

Animals↗

tGS ganglioside induces peculiar morphological features in grafted dopaminergic cells and promotes motor recovery in rats with unilateral lesions in the nigrostriatal dopamine pathway.

A cell suspension of substantia nigra from fetal rats was introduced into the ipsilateral caudate nucleus of rats with unilateral lesions in the nigrostriatal dopamine pathway, and effects of bovine total ganglioside (tGS) and monosialoganglioside (GM1) treatment on the morphological features of the transplanted cells and recovery from motor imbalance (rotation induced by methamphetamine) were investigated. Gangliosides (30 mg/kg) were administered intraperitoneally once a day for 2 weeks after transplantation to test animals while control animals received saline alone. tGS animals showed definite motor recovery in the 2nd week (P less than 0.05) while control and GM1 animals exhibited slight recovery only. At 6 weeks after transplantation, motor imbalance disappeared in all 3 groups. Tyrosine hydroxylase (TH) immunocytochemical staining revealed that in the 2nd week TH-positive cells in tGS animals had more primary dendrites and more large neurites (meganeurites) than did controls. TH-positive cells of all 3 groups often had spiny processes at that time. In the 20th week, TH-positive cells became more multigonal and had wider dendritic fields in all groups, and had less meganeurites and spines. Motor recovery of each animal was dependent on the number of TH-positive cells and no significant difference was observed in the number of TH-positive cells among the three groups. tGS treatment for 2 weeks without grafting induced immunohistologically no axonal sprouting in the substantia nigra, medial forebrain bundle, accumbens and caudate nucleus when the chemical lesions were complete. Data suggest that tGS induces hypertrophy but not hyperplasia of the transplanted nigral cells, and increases the morphological plasticity. This might be the basis for promotion of recovery in motor function after transplantation.

Animals↗

Long-term survival of grafted cells, dopamine synthesis/release, synaptic connections, and functional recovery after transplantation of fetal nigral cells in rats with unilateral 6-OHDA lesions in the nigrostriatal dopamine pathway.

In animal models of hemi-Parkinson's disease, survival of grafted nigral cells, their synaptic connections, dopamine (DA) synthesis/release, and recovery from motor disturbances were investigated, and these were compared among 3 groups of animals raised for 3 months, 1 year and 2 years after the transplantation. Fetal nigral DAergic cell suspensions were transplanted in the ipsilateral caudate nucleus of rats with unilateral 6-OHDA lesions in the nigrostriatal DA pathway. Motor disturbances, assessed by methamphetamine-induced rotation, recovered partly in the 2nd week, significantly in the 4th week after the grafting, and remained stable thereafter. Many tyrosine hydroxylase (TH)-positive cells were detected along the grafting tracks. The number of TH-positive cells was similar in the 3 groups of animals. These TH-positive cells made synaptic connections in the host caudate. By in vivo microdialysis measurement, extracellular DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) around the grafted sites recovered to 30-100% of those of controls. No significant differences were observed in the concentration of DA, DOPAC and HVA among 3 groups of animals. They also responded to methamphetamine loading though the magnitudes were smaller. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA in in situ hybridization-autoradiographic analysis. Data indicate that grafted fetal DAergic cells survive, synthesize and release DA, make synaptic connections in the host brain and ameliorate motor disturbances for over 2 years. There were no differences in these parameters among the 3 groups of animals, and no untoward side effects were observed even at 2 years after the grafting. Thus it was confirmed that the grafting of neuronal cells into the brain is a promising approach to restore disturbed function.

Animals↗

Behavioral and biochemical effects of intra-accumbens dopaminergic grafts.

6-Hydroxydopamine (6-OHDA) lesions in the ventral tegmental area (VTA) in rats prevented the hyperactivity response to methamphetamine in an open field. Transplantation of mesencephalic dopaminergic cells, obtained from rat embryos, into the nucleus accumbens (NAC) of 6-OHDA-lesioned animals restored the hyperactivity 4 weeks after grafting. By microdialysis of the NAC in freely moving rats no significant differences in baseline concentration of dopamine (DA) among the 3 groups (control, lesioned, grafted) were observed. However, after methamphetamine administration, DA increased significantly during the first 80 min in control animals, during the first 40 min in grafted animals, but did not increase in lesioned animals. On the other hand baseline concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased to one sixth to one third of those of controls in 6-OHDA-lesioned animals, and they did not respond to methamphetamine. After grafting, however, DOPAC and HVA restored to control levels and responded to methamphetamine with decreases as was observed in control animals. Data suggest that grafts not only restore the ability to release DA but also improve DA metabolism in the NAC. This might be a reason for recovery of locomotor activity.

3,4-Dihydroxyphenylacetic Acid↗

Phenotypic plasticity of grafted catecholaminergic cells in the dopamine-depleted caudate nucleus in the rat.

Catecholamine-producing cells were grafted in the caudate nucleus of model rats with hemi-Parkinson's disease--animals with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopaminergic pathway. Survival of the grafted cells, dopamine synthesis/release, and recovery from motor imbalance were investigated. Motor imbalance (methamphetamine rotations) recovered in more than 90% of animals by grafting of nigral dopaminergic (DAergic) cells, in 40-60% of animals by grafting of locus coeruleus noradrenergic (LC-NAergic) cells, and in 0-30% of animals by grafting of adrenal medullary cells. Many tyrosine hydroxylase (TH)-positive cells survived in the host caudate after grafting of DAergic cells. A moderate number of TH-positive but dopamine-beta-hydroxylase (DBH)-negative cells survived after grafting of NAergic cells. A few TH-positive neuron-like cells survived after grafting of adrenal medullary cells. In vivo microdialysis revealed that extracellular DA recovered up to 50-80% of that of control level, and dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) up to 25-50% of those of controls in animals that showed motor recovery after grafting. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA in an in-situ hybridization-autoradiographic study. Animals that received 6-OHDA lesion only or animals that received grafting but had no surviving cells showed neither behavioral nor chemical recovery. The data suggest that grafted catecholaminergic cells survive, make phenotypic plasticity, synthesize/release dopamine, and ameliorate motor function.

Adrenal Medulla↗