Effect of timing and dose of the hyperosmotic agent glycerol on experimental ischemic brain edema and metabolites.
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Biomedical subjects
Publications and source records attributed to A Terashi.
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Cerebral blood flow and metabolism in 25 patients with multiple cerebral infarcts (14 with dementia) and 5 healthy age-matched controls were measured to investigate the difference in cerebral blood low (CBF) and cerebral oxygen consumption (CMRO2) between patients with dementia and patients without dementia. None of the patients had any lesions in the cortex, but all had multiple lesions in the basal ganglionic region, and in the white matter, according to CT images. CBF, CMRO2 and oxygen extraction fraction were measured by positron emission tomography (PET) using the 15O2, C15O2 steady state inhalational technique. In patients with multiple cerebral infarcts the absolute values of CBF and CMRO2 were decreased significantly from normal control values, and there was no significant difference in the absolute values of CBF and CMRO2 between patients with dementia and patients without dementia. In most patients with dementia, relative values (regional value/mean cortical value) of CBF and CMRO2 decreased in the frontal and the parietal cortex. Four patients had repeated PET studies. In two of them, decrease in CMRO2 was preceded by decrease in CBF. These results suggest that dysfunction of frontal cortex and parietal cortex, and chronic ischemia might be related to the occurrence of dementia in patients with multiple cerebral infarcts, which were in the basal ganglia and the white matter.
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Glucose metabolism is altered in various pathologic conditions in the brain, i. e. ischemia, epilepsy and hypoglycemia. Therefore, analysis of glucose metabolism in pathologic conditions needs careful investigation of that in steady state. 13C-NMR method allows continuous sequential monitoring of changes in metabolism of glucose in vivo. The natural abundance of 13C is quite low (1.1%) and by administering 13C labelled in various skeleton in glucose, it is possible to monitor the metabolites in vivo. In this study, 13C glucose labelled in 1-position of carbon was employed to investigate the metabolic pathways in the control and transient ischemic gerbil brain with reperfusion. Male mongolian gerbils weighing 60-80 g were employed in this study. The gerbils were anesthetized by intraperitoneal administration of pentobarbital. The right skull was exposed and a surface coli was placed directly above the skull bone. After the operation, the animals were fastened to the NMR probe vertically. 500 mg/kg of [1-13C] glucose was injected via femoral catheter. 13C-NMR spectra were serially obtained before and after injection with GX-270 NMR spectrometer (JEOL, Tokyo, Japan, 6.34 T). In other series of experiments, 30 minutes of cerebral ischemia were induced after 15 minutes of glucose injection by the bilateral common carotid artery occlusion. In the normal gerbil brain, after administration of [1-13C] glucose (500 mg/kg), alpha and beta-anomers of [1-13C] glucose peak appeared abruptly and reached its peak level at 7.5-15 min acquisition period. The C2 peak representing glutamate and/or glutamine appeared later. The C3 and C4 peak started to appear even later at 30-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Cerebrotendinous Xanthomatosis (CTX) is a rare familial disease characterized by tendon-xanthomas, cataracts, progressive cerebellar ataxia, dementia and an elevation of serum cholestanol with normal levels of cholesterol. Although the pathogenesis of CTX is not fully understood, increment of cholestanol is suggested one of the major metabolic derangements of the disease. Recently, the LDL-apheresis has been developed as a new therapeutical equipment in the field of hyperlipidemia and been widely used to reduce the levels of LDL-cholesterol by selective LDL adsorption. From the point of view that cholestanol is involved mainly in LDL-cholesterol (1.019 less than d less than 1.063), we used this LDL-apheresis in the aim of reducing the cholestanol in 58 years old woman with typical sign and symptoms of CTX. The levels of serum cholestanol and cholesterol before the treatment with LDL-apheresis, were 10.7 micrograms/ml and 175 mg/dl respectively. Also the ratio of cholestanol/cholesterol indicated 0.63. By the first procedure of apheresis, the level of cholestanol was markedly decreased to 5.2 micrograms/ml (50%). Several LDL-apheresis treatments were carried out once a month. During 5 months treatments, neurological deterioration was arrested, dementia which included disorientation and recent-memory loss, cleaned a little. Although the xanthomas did not decrease in size, this patients was better oriented to person, place, time and was able to speak rationally, 2nd her cerebellar dysfunction revealed improvement. From our new experiments-we believe that the LDL-apheresis offers the strong hope of preventing the progress on cerebrotendinous xanthomatosis.
A 50-year-old woman developed third, fourth, and fifth cranial nerve palsies in the right associated with frontal pain in the ipsilateral side. Oral administration of prednisolone (30 mg/day) was initiated. The painful ophthalmoplegia improved dramatically following this treatment. Three months later, the patient developed the third, fourth, and fifth cranial palsies in the left which was contralateral to the previous episode. The patient had pain in the left frontal region. The corticosteroid therapy was again effective. Cavernous sinus and orbital venographies demonstrated a constriction of the right superior ophthalmic vein in the first and third parts, with a partial filling of the cavernous sinus. The left superior vein and cavernous sinus were normal. A left carotid arteriogram showed a slight deformity of the carotid siphon in the left. The glucose tolerance test demonstrated a mild diabetic pattern. Diabetic ophthalmoplegia can also be suspected in this case, however, the finding of a partial filling of the right cavernous sinus was indicative of Tolosa-Hunt syndrome. Therefore this case was diagnosed as Tolosa-Hunt syndrome. Alternating relapsing Tolosa-Hunt syndrome involving the third, fourth and fifth cranial nerve as seen in this case is very rare. There are many diseases which may demonstrate similar symptoms; i.e. parasellar tumor, aneurysm, diabetic ophthalmoplegia, multiple cranial neuropathy, etc. The pathologic process involved in Tolosa-Hunt syndrome is poorly understood and it appears that the clinical entity of this syndrome should be questioned. We believe that it is necessary to clarify the precise pathologic process involved in this syndrome and its relation with other similar syndromes exhibiting similar symptoms.
In this study we report and compare plasma leukotriene (LT) levels in seventeen (17) patients with cerebral infarction, five (5) patients with cerebral hemorrhage and twelve (12) age-matched healthy volunteers. Plasma samples were collected at intervals of 1-7 days, 8-14 days, 15-30 days and 31 days- after cerebrovascular accident. Plasma immunoreactive LTC4, LTB4 and SRS-A (Slow Reacting Substance of Anaphylaxis or total peptido-LT's) levels were measured for each sample. Immunoreactive LTC4 (and SRS-A) levels were elevated in patients with cerebral infarction whilst LTB4 levels were raised in the patients with cerebral hemorrhage. In particular, cerebral infarcted patients exhibited significantly elevated levels in phases 1-7 days and after 15 days when compared with the age-matched healthy volunteers. In patients with cerebral hemorrhage, significant increases in LTB4 were measured in days 1-7 only. These results suggest a clinical relationship between the plasma levels of LT's and cerebrovascular disease.
The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema.
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The distribution of cerebral blood flow and metabolism is related to neuronal activity. Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) in ten patients with Parkinson's disease and five age-matched normal control subjects were measured with positron emission tomography (PET) using 15O2, C15O2 steady state inhalational technique to investigate functional changes of the cortex and the basal ganglia in Parkinson's disease. All patients had no history of cerebrovascular disease and CT scan showed no abnormal findings except for moderate cerebral atrophy in only one patient. When the level of clinical disability was related on the scale of Hoehn and Yahr, one patient was stage I, four were stage II, four were stage III, and one was stage IV. Psychic symptoms which include hallucination, depression, and dementia were recognized in four patients. One of these four patients was mildly demented. Four patients were newly diagnosed and had never been treated with antiparkinsonian medication before. Before the patients had their PET study their antiparkinsonian medication was discontinued for more than three days. But in two patients PET study was performed without discontinuity of antiparkinsonian medication. The values for regional CBF and regional CMRO2 were lower in the patients than in the normal control subjects, especially in the frontal cortex there was a significant decrease of CBF and CMRO2. There was no discrepancy between CBF and CMRO2 both in the patients and the normal control. CBF and CMRO2 in the cortex and the basal ganglia were not correlated with the severity of tremor, bradykinesia, and rigidity.(ABSTRACT TRUNCATED AT 250 WORDS)
Using two different models of non ischemic and transient cerebral ischemia in SHR, the effect of hyperosmolar solution with intravenous 10% glycerol on serum lipid peroxides, plasma prostaglandins (TXA2, PGI2), brain water content and brain metabolites were studied. Glycerol did not influence the levels of lipid peroxides, plasma prostaglandins and brain water content in the non ischemic rats. In the transient ischemia group, on the other hand, serum lipid peroxides were significantly reduced in the glycerol administrated group. On the study of plasma prostaglandins, there was no difference of TXA2 levels between two groups, but PGI2 levels were significantly increased in the glycerol administrated group. Brain water content was significantly decreased. And on the study of brain metabolites, ATP concentrations remained higher and lactate concentrations were lower in the glycerol administrated group compared with those in the control group. But there was no difference with pyruvate concentrations between two groups, furthermore L/P ratio improved in the glycerol administrated group. Besides the effect on reduction of brain edema as for hyperosmolar solution, glycerol may indicate improvement of ischemic impediments on brain by the action of antioxidation and reinforcement of PGI2.
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Arachidonic acid (AA) is a potent stimulator of platelet aggrgation and is known to induce endothelial cell damage and edema in the brain. An ischemic cerebral infarction model can be produced in rats by an internal carotid infusion of AA. In this study, water content, ATP and lactate in the brain and plasma prostaglandins (thromboxane B2; TXB2 and 6-keto-prostaglandin F1 alpha; 6-keto-PGF1 alpha) were measured and histological observations were made after an internal carotid infusion of AA in two strains of rats; stroke-resistant spontaneously hypertensive rat (SHRSR) and normotensive Wistar-Kyoto (WKY) rats. It is known that the blood pressure of the SHRSR begins to rise at about 8 weeks old. Throughout the study, AA was administered into the internal carotid artery under 2% fluothane anesthesia. In the first study, AA (1.7 mg/kg BW) was administered to 8- and 16-week-old rats and the length of survival was observed. In the second study, water content, ATP and lactate in the brain and plasma TXB2 and 6-keto-PGF1 alpha were measured 3 hours after AA (0.85 mg/kg BW) administration. In the third study, rats were perfusion-fixed 3 hours after the AA (1.7 mg/kg BW) infusion and cerebral arteries were observed by scanning electron microscopy (SEM). During the 6 hour observation period, there was no difference between the two groups in the number of 8-week-old rats which survived. However, the figure became significantly lower in the SHRSR at 16 weeks old. The water content in the bilateral cerebral hemispheres was significantly larger in the SHRSR than in the WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)