[Agents for treatment of brain edema].
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Biomedical subjects
Publications and source records attributed to A Terashi.
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In order to investigate the relation between auditory cognitive function and regional brain activation, we measured the changes in the regional cerebral blood flow (CBF) using positron emission tomography (PET) during the "odd-ball" paradigm in ten normal healthy volunteers. The subject underwent 3 tasks, twice for each, while the evoked potential was recorded. In these tasks, the auditory stimulus was a series of pure tones delivered every 1.5 sec binaurally at 75 dB from the earphones. Task A: the stimulus was a series of tones with 1000 Hz only, and the subject was instructed to only hear. Task B: the stimulus was a series of tones with 1000 Hz only, and the subject was instructed to push the button on detecting a tone. Task C: the stimulus was a series of pure tones delivered every 1.5 sec binaurally at 75 dB with a frequency of 1000 Hz (non-target) in 80% and 2000 Hz (target) in 20% at random, and the subject was instructed to push the button on detecting a target tone. The event related potential (P300) was observed in task C (Pz: 334.3 +/- 19.6 msec). At each task, the CBF was measured using PET with i.v. injection of 1.5 GBq of O-15 water. The changes in CBF associated with auditory cognition was evaluated by the difference between the CBF images in task C and task B. Localized increase was observed in the anterior cingulate cortex (in all subjects), the bilateral associate auditory cortex, the prefrontal cortex and the parietal cortex. The latter three areas had a large individual variation in the location of foci.(ABSTRACT TRUNCATED AT 250 WORDS)
We reported a 67-year-old male, who suffered from apraxia and amnesia for 2 years and for muscle rigidity of right extremities for a year. Neurological examination revealed dysarthria, dysphagia, marked dystonia of right arm, hyperreflexia of all limbs and ataxic gait. He also had dementia and many other higher cortical dysfunction mostly due to left hemisphere damage. No impairment of eye movement was disclosed. Brain MRI as well as CT showed the significant brain atrophy in the left parieto-occipital region. A degenerative atrophy was suspected by 123I-IMP-SPECT and 18F-FDG-PET. By FDG-PET, the decrease of cerebral blood flow and glucose metabolism was detected not only affected unilateral cerebral cortex including primary motor area but ipsilateral basal ganglia and thalamus. Although, it is difficult to distinguish clinically CBD from atypical case of Alzheimer's disease, we speculated that in early stage of dementia, significant unilateral hypoperfusion and hypometabolism of basal ganglia and thalamus is characteristic of CBD.
A PGI2 derivative, OP-41483, and a hyperosmotic agent, glycerol, were tested for possible beneficial effects on brain edema, metabolism and pathological changes in cerebral ischemia. Combination treatment with these agents was also tested. Cerebral ischemia was produced in spontaneously hypertensive rats, using bilateral common carotid artery ligation (BLCL). OP-41483 was administered four times, hourly (500 ng/kg x 4, i.p.). Ten percent glycerol was administered intravenously (6.6 ml/kg). And, for the combination treatment, OP-41483 was administered three times, hourly (500 ng/kg x 3, i.p.), and 10% glycerol was administered intravenously (6.6 ml/kg) in the same manner as the glycerol treated group. In ischemic controls, saline was administered intravenously (6.6 ml/kg). After 3 h of ischemia, brain water content and metabolites were determined and pathological observation was conducted using electron microscopy. OP-41483 treated animals maintained higher levels of ATP concentration and reduced accumulation of lactate, but showed no difference in brain water content compared to saline treated controls. Glycerol treated animals showed significance in terms of reduction of brain water content and accumulation of lactate. Glycerol abated the depletion of ATP concentration. OP-41483+glycerol treated animals showed the most significant effect on the reduction of brain water content and accumulation of lactate. The combination treatment also maintained higher levels of ATP concentration. Additionally, swelling of astrocytic foot processes and mitochondria with destroyed crista were not observed pathologically in the combination treated animals. These results show that OP-41483, glycerol and combination treatment are beneficial in the treatment of cerebral ischemia. They also indicate that the combination treatment significantly enhances the protective effects compared to individual treatment.
Effect of indomethacin on post-ischemic changes of CA1 neurons was studied in the hippocampus of the Mongolian gerbil. The gerbil was employed because due to poor development of posterior communicating artery ischemia could be easily induced in the forebrain simply by occluding bilateral common carotid arteries. Indomethacin (5 mg/kg, i.p.) was administered 30 min before the occlusion. The occlusion lasted for 5 divided into four groups. In one group, the temperature was not controlled. In the remaining three groups, the temperature was kept at 35.5 degrees C, 37.5 degrees C, and 39.5 degrees C, respectively. Seven days after the occlusion neuronal density was assessed on histological sections stained with hematoxylin eosin. It was found that in all groups indomethacin was effective in preventing delayed neuronal death regardless of the difference in the cranial temperature. However, delayed neuronal death was the least in the lowest temperature group. The drug also prevented the post-ischemic hyperthermia observed in the temperature non-controlled group. These results indicate that indomethacin has its own pharmacological action to prevent delayed neuronal death.
We studied the correlation between clinical and CT-findings in 33 cases with hemiballismus. Of these 33 cases, 4 cases were examined by the authors and 29 cases were obtained from the literature. Cerebrovascular disease was present in 27 cases and the localization of the lesion was examined with CT. Of these 10 cases had lesions in the subthalamus, while 17 cases had lesions outside the subthalamus. In 6 cases, the location of the lesion was not recognized on CT. In cases with lesions outside the subthalamus, 11 cases had lesions in the putamen, 10 cases had lesions in the caudate. Therefore the lesion were largely located in the striatum. Typical hemiballismus was seen in 16 cases. In this group, 6 cases had lesions in the subthalamus, 5 cases had lesions in the putamen, and 3 cases had lesions in the caudate. Hemiballismus accompanied by hemichorea was seen in 17 cases. In this group, while 9 cases had hemichorea with ballismus, and 5 out of 9 cases had lesions in the caudate, 4 cases had lesions in the putamen. Thus, all lesions were located in the striatum. Eight out of 17 cases had hemiballismus with chorea. In these 8 cases, 4 cases had lesions in the subthalamus, these were 2 cases in the putamen, and 2 cases had lesions in the caudate. When all cases were examined in terms of clinical manifestations, 10 cases were considered to have lesions in the caudate and 7 out of 10 cases involved chorea. Ten cases had lesions in the subthalamus, while 6 out of 10 cases showed typical hemiballismus.(ABSTRACT TRUNCATED AT 250 WORDS)
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A 51-year-old woman, with progressive gait disturbance and dysarthria, had been diagnosed as Menzel-type spinocerebellar degeneration. Later, she developed dystonic posture of upper limbs and bulging eyes. She was diagnosed as Machado-Joseph disease from neurological findings, which consisted of cerebellar signs, pyramidal tract signs and extrapyramidal tract signs and peripheral neuropathy. She died suddenly of unknown origin. Her illness lasted about 13 years. Neuropathological findings showed moderate neuronal loss with gliosis in the subthalamic nucleus, globus pallidus, substantia nigra, dentate nucleus, oculomotor and hypoglossal nucleus and anterior horn. Positron emission tomography (PET) using 15O steady state inhalation technique revealed reduction of cerebral blood flow and cerebral metabolic rate of oxygen in not only cerebellum but also cerebral cortex. These findings are different from typical PET findings of spinocerebellar degeneration.
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It is said that maintenance hemodialysis patients are already suffering from secondary hyperparathyroidism (2HPT) from early stage of chronic renal failure. The treatment of 2HPT in this stage is very important for preventing renal osteodystrophy (ROD). But many long-term dialysis patients are still afflicted with ROD although vitamin D have been used for treatment. In this study, an oral administration of 1-25 (OH)2 D3 (4 micrograms) with pulse therapy twice a week at the day before hemodialysis was started for 12 weeks. The concentration of 1-25 (OH)2D3, total calcium (Ca), ionized calcium (Ca++), alkaline phosphatase (ALP) and parathyroid hormone (PHT) in serum were measured not only before and after every 2 hours of administration a day, but also for 12 weeks after that. The peak of serum 1-25 (OH)2D3 could be sufficiently elevated after 8 hours, and the slight peak of Ca++ could be seen after 8 hours as well. But the level of total calcium could not increased. Although the level of only HS-PTH has not increased after 24 hours, a significant reduction in serum level of C-PTH, intact-PTH and HS-PTH could be recognized after 12 weeks finally. This pulse therapy was effective in reducing the serum level of PTH in this early stage from beginning hemodialysis. But, it needs further studies for the standard treatment.
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A 51-year-old man developed muscle weakness of the bilateral upper extremities, and mental changes beginning with personality change. There was no history of mental illness in his family. A neurological examination 1 year after the onset revealed muscle atrophy and fasciculation of his bilateral upper extremities Neuropsychological examination revealed concrete speech, paraphasia, and lack of judgment. Disorientation, amnesia, dyscalculia, and spatial agnosia, however, were not recognized. These neuropsychological findings were compatible with dementia of frontal lobe type. EMG and muscle biopsy revealed neurogenic muscular atrophy. There was no abnormal findings in the brain X-CT and the brain MRI. PET study using C15O2 and 15O2 revealed reduction of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in the bilateral medial frontal cortex, the left temporal cortex and the bilateral thalamus. From these these findings the patient was diagnosed as having motor neuron disease with dementia. Muscle atrophy and dementia worsened gradually. A second PET study 2 years and 6 months after the onset revealed severe reduction of CBF and CMRO2 in the bilateral temporal cortex and the thalamus. These PET findings suggested that dysfunction of the temporal cortex and the thalamus related to dementia in this case.
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