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Biomedical subjects

Yoshiaki Itoh

Publications and source records attributed to Yoshiaki Itoh.

At least 19 recordsLinked to original sources

Reactive oxygen species generated by mitochondrial injury in human brain microvessel endothelial cells.

Generation of reactive oxygen species (ROS) and their detrimental effects on the brain after transient ischemia are widely recognized. We studied ROS production from mitochondria in human brain microvessel endothelial cells (HBEC) under chemical hypoxia. HBEC in confluent conditions were incubated for 30 min with 10 microM 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein (DCF) diacetate, which was hydrolyzed and trapped inside the cells. ROS were measured with a fluorescent microscope, a CCD camera and an image analyzing system. Injury to mitochondrial respiratory chain was induced either with rotenone (an inhibitor of mitochondrial complex I) or with m-chlorocarbonyl cyanide phenylhydrazone (CCCP) (an uncoupler of ATP synthetase). Shortly after application of 10 microM rotenone, fluorescent intensity started to increase and the gradual increase continued for 10 min. Similarly, CCCP (10, 50 and 100 microM) dose-dependently increased the fluorescent intensity (p<0.01). Edaravone, a free radical scavenger widely used for treatment of cerebral infarction in Japan, at 100 microM successfully suppressed this ROS production (p<0.05). These data show that chemical hypoxia with normal concentration of oxygen in the medium induced free radicals generation in HBEC. Importance of endothelial mitochondria as a source of free radicals after reperfusion is suggested.

Antipyrine↗

Apoptosis induced by 7-ketocholesterol is enhanced in smooth muscle cells derived from OLETF rats.

To clarify whether an increased proliferative potential of vascular smooth muscle cells (SMC) under diabetic conditions augments the susceptibility of the cells to 7-ketocholesterol-induced apoptosis, we investigated the difference in sensitivity to 7-ketocholesterol between SMC obtained from diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and the control Long-Evans Tokushima Otsuka (LETO) rats. The outgrowth rate from aortic wall explants and cell proliferation were higher in SMC derived from OLETF rats (OLETF-derived SMC) compared to those from LETO rats (LETO-derived SMC). When 7-ketocholesterol was added to SMC, the amount of fragmented DNA increased significantly in OLETF-derived compared to LETO-derived SMC. The amount of fragmented DNA induced by 7-ketocholesterol decreased significantly in both OLETF- and LETO-derived SMC when they were incubated without fetal bovine serum. By adding PDGF-BB to LETO-derived SMC, the amount of fragmented DNA induced by 7-ketocholesterol increased significantly. These results suggest that apoptosis of SMC induced by 7-ketocholesterol may be accelerated when SMC acquire a high proliferative potential by prolonged exposure to diabetic condition.

Animals↗

Beneficial effect of low carbohydrate in low calorie diets on visceral fat reduction in type 2 diabetic patients with obesity.

The adequate composition of carbohydrate and fat in low calorie diets for type 2 diabetes mellitus patients with obesity is not fully established. The aim of this study was to investigate the effects of low carbohydrate diet on glucose and lipid metabolism, especially on visceral fat accumulation, and comparing that of a high carbohydrate diet. Obese subjects with type 2 diabetes mellitus were randomly assigned to take a low calorie and low carbohydrate diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat = 25:40:35) or a low calorie and high carbohydrate diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat = 25:65:10) for 4 weeks. Similar decreases in body weight and serum glucose levels were observed in both groups. Fasting serum insulin levels were reduced in the low carbohydrate diet group compared to the high carbohydrate diet group (-30% versus -10%, P < 0.05). Total serum cholesterol and triglyceride levels decreased in both groups, but were not significantly different from each other. High-density lipoprotein-cholesterol (HDL-C) increased in the low carbohydrate diet group but not in the high carbohydrate diet group (+15% versus 0%, P < 0.01). There was a larger decrease in visceral fat area measured by computed tomography in the low carbohydrate diet group compared to the high carbohydrate diet group (-40 cm(2) versus -10 cm(2), P < 0.05). The ratio of visceral fat area to subcutaneous fat area did not change in the high carbohydrate diet group (from 0.70 to 0.68), but it decreased significantly in the low carbohydrate diet group (from 0.69 to 0.47, P < 0.005). These results suggest that, when restrict diet was made isocaloric, a low calorie/low carbohydrate diet might be more effective treatment for a reduction of visceral fat, improved insulin sensitivity and increased in HDL-C levels than low calorie/high carbohydrate diet in obese subjects with type 2 diabetes mellitus.

Adipose Tissue↗

Fluorometric determination of glucose utilization in neurons in vitro and in vivo.

Glucose is the major energy source the adult brain utilizes under physiologic conditions. Recent findings, however, have suggested that neurons obtain most of their energy from the oxidation of extracellular lactate derived from astroglial metabolism of glucose transported into the brain from the blood. In the present studies we have used 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a fluorescent analogue of 2-deoxyglucose, which is often used to trace glucose utilization in neural tissues, to examine glucose metabolism in neurons in vitro and in vivo. Cultured neurons and astroglia were incubated with 2-NBDG for up to 15 minutes, and nonmetabolized 2-NBDG was washed out. We found that fluorescence intensity increased linearly with incubation time in both neurons and astroglia, indicating that both types of brain cells could utilize glucose as their energy source in vitro. To determine if the same were true in vivo, Sprague-Dawley rats were injected intravenously with a pulse bolus of 2-NBDG and decapitated 45 minutes later. Examination of brain sections demonstrated that phosphorylated 2-NBDG accumulated in hippocampal neurons and cerebellar Purkinje cells, indicating that neurons can utilize glucose in vivo as energy source.

4-Chloro-7-nitrobenzofurazan↗

Frequent word section extraction in a presentation speech by an effective dynamic programming algorithm.

Word frequency in a document has often been utilized in text searching and summarization. Similarly, identifying frequent words or phrases in a speech data set for searching and summarization would also be meaningful. However, obtaining word frequency in a speech data set is difficult, because frequent words are often special terms in the speech and cannot be recognized by a general speech recognizer. This paper proposes another approach that is effective for automatic extraction of such frequent word sections in a speech data set. The proposed method is applicable to any domain of monologue speech, because no language models or specific terms are required in advance. The extracted sections can be regarded as speech labels of some kind or a digest of the speech presentation. The frequent word sections are determined by detecting similar sections, which are sections of audio data that represent the same word or phrase. The similar sections are detected by an efficient algorithm, called Shift Continuous Dynamic Programming (Shift CDP), which realizes fast matching between arbitrary sections in the reference speech pattern and those in the input speech, and enables frame-synchronous extraction of similar sections. In experiments, the algorithm is applied to extract the repeated sections in oral presentation speeches recorded in academic conferences in Japan. The results show that Shift CDP successfully detects similar sections and identifies the frequent word sections in individual presentation speeches, without prior domain knowledge, such as language models and terms.

Algorithms↗

Complications in adults with growth hormone deficiency--a survey study in Japan.

It has been reported that adult patients with growth hormone deficiency (GHD) have increased risk factors for cardiovascular disorders in Western countries. However, data on this issue in Japan have not been fully investigated. To clarify the situation on this issue in Japan, a nationwide questionnaire survey was conducted by Study Group of Hypothalamo-Pituitary Disease, and medical records of 863 adult patients were recruited. The incidences of complications and risk factors for cardiovascular diseases were compared between GH deficient patients (GHD, n = 494) and GH intact patients (GHI, n = 369). The incidence of myocardial infarction was higher in GHD (1.2%) than in GHI (0.8%), but not significantly. The incidences of angina pectoris and liver dysfunction were significantly higher in GHD than in GHI (2.8 vs 0.8%, p = 0.048, and 11.9 vs 5.5%, p<0.0001, respectively). The prevalences of obesity and hyperlipidemia (HL) were significantly higher in GHD (p = 0.004, p<0.001, respectively). Combinations of HL plus diabetes mellitus (DM) or hypertension (HT) were more common in GHD than in GHI (HL + DM; 7.2 vs. 2.9%, HL + HT; 10.9 vs. 2.9%). These results indicated that GH deficiency have an increased prevalence of cardiovascular risk factors in Japanese similar to Western countries, and suggested that GH supplement therapy may be needed to reduce those complications.

Adult↗

Reaction and characterization of thioamide dianions derived from N-benzyl thioamides.

Thioamide dianions were generated by the highly efficient reaction of N-benzyl thioamides with 2 equiv of BuLi. Alkylation, allylation, and silylation took place selectively at the carbon atom adjacent to the nitrogen atom of the thioamide dianions. Oxiranes and an aldehyde were also used as electrophiles in the reaction of thioamide dianions to form N-thioacyl 1,3- or 1,2-amino alcohols. The insertion reaction of elemental sulfur to a thioamide dianion and subsequent ethylation afforded a N-thioacyl hemithioaminal. NMR studies on the thioamide mono- and dianions derived from N-benzyl 2-methoxythiobenzamide showed a linear relationship between the chemical shifts of all carbon atoms of thioamide mono- and dianions. The results also suggested that the negative charge at the benzylic carbon atom of the dianion is not fully delocalized. The charge distribution patterns of the dianion are consistent with those of pi polarization.

Journal Article↗

Occurrence of two distinct types of tissue inhibitor of metalloproteinases-2 in teleost fish.

We have cloned for the first time two cDNAs encoding distinct types of tissue inhibitor of metalloproteinases-2 (TIMP-2) from teleost fish, Japanese flounder, and designated these types as jfTIMP-2a and jfTIMP-2b. The open reading frames of the jfTIMP-2a and jfTIMP-2b cDNAs are composed of 663 and 657 nucleotides and 221 and 219 amino acids, respectively. Both jfTIMP-2s contain 12 cysteine residues, which might form six disulfide bonds as in other animals' TIMP-2s. The predicted full-length amino acid sequence of jfTIMP-2a has lower identity to jfTIMP-2b (63%) than to those of human (74%) and chicken (73%) TIMP-2s, but higher than to those of other human TIMPs (TIMP-1: 39%, TIMP-3: 43%, TIMP-4: 45%), indicating that jfTIMP-2a is a common TIMP-2, while jfTIMP-2b is unique to Japanese flounder. However, the C-terminal region including the last three disulfide bonds of jfTIMP-2b has higher amino acid identity to those of other animal TIMP-2s than to that of jfTIMP-2a. Reverse-transcribed polymerase chain reaction (RT-PCR) analysis showed the mRNAs of jfTIMP-2a and jfTIMP-2b to be ubiquitously expressed in all tissues examined, but with different expression patterns. These findings suggest that the two distinct jfTIMP-2s might perform different functions in teleost tissues.

Amino Acid Sequence↗

Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

Animals↗

Inhibition of [18F]FP-TZTP binding by loading doses of muscarinic agonists P-TZTP or FP-TZTP in vivo is not due to agonist-induced reduction in cerebral blood flow.

[(18)F][3-(3-(3-Fluoropropyl)thio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine ([(18)F]FP-TZTP) is an M2 selective muscarinic agonist that may allow noninvasive studies of Alzheimer's disease with PET. 3-(3-(Propylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (P-TZTP), a nonfluorinated analog of FP-TZTP, and unlabeled FP-TZTP inhibited [(18)F]FP-TZTP binding in vivo. Because muscarinic action of the loading dose of P-TZTP administered might have had pharmacological effects, the apparent inhibition might have resulted from reduced delivery rather than competition with receptor-binding. Therefore, we examined the effects of P-TZTP or FP-TZTP administration on cerebral blood flow (CBF) measured by the [(14)C]iodoantipyrine method and laser-Doppler flowmetry in rats. Statistically significant synchronous decreases in both CBF and mean arterial blood pressure (MABP) were observed within the first minute following administration. The decreases in both CBF and MABP were prevented by pretreatment with atropine methyl bromide (M-At), a peripheral muscarinic antagonist, and coadministration of M-At with either FP-TZTP or P-TZTP resulted in the same degree of inhibition of cerebral [(18)F]FP-TZTP-uptake 30 min after administration as observed without M-At. Also, with programmed infusions designed to produce constant arterial concentrations of [(18)F]FP-TZTP and FP-TZTP, which avoid changes in CBF, significant inhibition of [(18)F]FP-TZTP-binding by FP-TZTP was observed. These results indicate that inhibition of [(18)F]FP-TZTP-binding in the brain by P-TZTP or FP-TZTP in vivo occurs independently of their effects on CBF. The methods employed here may also be of interest to evaluate physiological effects of blocking agents utilized to validate other radiopharmaceuticals.

Animals↗

Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer.

In search of an efficient transdermal drug delivery system (TDDS), a polyhydroxyalkanoate (PHA)-based system with a polyamidoamine dendrimer was examined. Tamsulosin was used as the model drug. The dendrimer was found to act as the weak enhancer. By adding the dendrimer, the dendrimer-containing PHA matrix achieved the clinically required amount of tamsulosin permeating through the skin model. This is also the first report of the application of PHA and dendrimer to the TDDS.

Journal Article↗

Mechanism of enhancement effect of dendrimer on transdermal drug permeation through polyhydroxyalkanoate matrix.

The possible application of polyhydroxyalkanoate (PHA) in transdermal drug delivery systems (TDDSs) for tamsulosin was previously reported. PHAs containing the drugs, ketoprofen, clonidine and tamsulosin showed good adhesiveness to the skin model used, that is, shed snake skin, and dispersed well all model drugs tested. The model drugs hardly permeated through snake skin in solution form. However, these drugs permeated well through snake skin from the PHA matrix. It was previously reported that the addition of a dendrimer, a polymeric permeation enhancer, is effective for the TDDS for tamsulosin to establish an effective clinical TDDS. The effect of dendrimer addition was examined in TDDSs for ketoprofen and clonidine. The dendrimer added did not show an enhancement effect on the TDDSs for the two drugs. To investigate the mechanism of the enhancement effect of a dendrimer on the tamsulosin TDDS, X-ray analyses were performed. With dendrimer addition, drug crystallization in PHA was promoted. The crystal in PHA had highly ordered and changed its space group. These findings are very important for exploiting high-performance PHA-based TDDSs.

Journal Article↗

[Establishment and effect of the drug safety management monitoring system].

Early detection and early treatment of adverse drug reactions have recently become more important. It is natural that physicians should treat adverse drug reactions carefully, but it is also important to establish a system for their early systematic detection and treatment. Therefore, by comparing current data with that preserved in our clinical laboratory's data management registry and identifying values significantly different from earlier values, we established a screening system for any condition which may have a possible relationship with drugs and feeds back the results to the physician(s) in charge (drug safety management monitoring system). The effectiveness of the system was then evaluated. The subjects were outpatients who visited the Diabetes Endocrine Metabolism Center of our hospital during a six-month period. Cases where the possibility of a relationship between abnormal changes of laboratory data and drugs was not ruled out were reported to the attending physician using a drug safety monitoring report form. In 14 of 34 cases reported, a relationship with drugs could not be ruled out. Two of these 14 cases were reported to the Ministry of Health, Labour and Welfare because they were serious. Therefore, it was concluded that this system was useful for early detection of adverse reactions.

Adverse Drug Reaction Reporting Systems↗

[SPECT imaging using [123I]beta-CIT and [123I]IBF in extrapyramidal diseases].

Imaging of dopaminergic function is useful in the investigation of patients with Parkinson disease (iPD) and other extrapyramidal diseases. Using agents that bind to dopamine transporters ([123I]beta-CIT) and receptors ([123I]IBF SPECT), we investigated SPECT in 9 healthy volunteers and 24 patients for dopamine transporters as well as 15 patients for dopamine receptors. In beta-CIT SPECT studies, we examined 17 iPD patients (63.3 +/- 9.9 y/o), 3 multiple system atrophy (MSA) patients (OPCA type) (64.0 +/- 8.0 y/o), 2 vascular parkinsonism (VP) patients (71.0 +/- 0.0 y/o), 1 progressive supranuclear palsy (PSP) patient (69 y/o), 1 cortico-basal degeneration (CBD) patient (50 y/o) and nine healthy controls (39.1 +/- 9.3 y/o). For IBF SPECT studies 11 iPD patients (60.6 +/- 10.9 y/o), 3 MSA patients (2 OPCA type (50.5 +/- 3.5 y/o) and 1 SND type (65 y/o)) and 1 PSP patient (60 y/o) underwent SPECT scans after the injection of [123I]IBF. The specific to nonspecific striatal uptake ratio(St/Oc-1), ratio of putaminal uptake to caudatal uptake (Pu/Ca), and asymmetry indices (AI) were estimated. beta-CIT studies showed St/Oc-1 as follows; iPD: 2.66 +/- 1.09 (n = 17), VP: 5.73 and 7.39, MSA: 1.84 +/- 0.46 (n = 3), PSP: 2.34, CBD: 2.16. In all extrapyramidal diseases except VP, St/Oc-1 ratios were significantly lower than those in normal volunteers (6.46 +/- 1.08) (p < 0.01). Also in early-phase iPD patients (Yahr I-II), St/Oc-1 (3.16 +/- 1.49: n = 4) was significantly lower than those in normal volunteers (p < 0.01). In IBF studies, St/Oc-1 ratios were significantly higher in early-phase (Yahr I-II) iPD patients (1.82 +/- 0.25: n = 5) than those in late-phase (Yahr III-IV) iPD patients (1.38 +/- 0.32: n = 6) (p < 0.05). The Pu/Ca ratios in iPD patients (1.12 +/- 0.13) and MSA (OPCA type) patients (0.95 +/- 0.05) were higher than that in MSA (SND type) patient (0.78) and were lower than that in PSP patient (1.55). In conclusion, beta-CIT-SPECT is useful for the diagnosis of early-phase iPD patients and for differentiating VP from other extrapyramidal diseases. IBF-SPECT is useful for the diagnosis of the severity of iPD and has the possibility for ruling out MSA (SND type) or PSP from iPD. Both tracers are useful for investigating the pathophysiology of patients with iPD and other extrapyramidal diseases.

Aged↗

Blockade of K(ATP) channels with glibenclamide does not alter functional activation of cerebral blood flow in the unanesthetized rat.

Possible involvement of ATP-sensitive K(+) (K(ATP)) channels in the cerebral blood flow (CBF) response to neuronal functional activation was investigated in unanesthetized rats. Glibenclamide (1, 2, or 10 micromol/l), a specific inhibitor of K(ATP) channels, was infused intracisternally continuously for 30 min prior to and during the 1-min period of measurement of CBF. Unilateral functional activation was maintained throughout the measurement of CBF by continuous stroking of the vibrissae on the left side of the face. Local CBF was determined bilaterally by the quantitative autoradiographic [14C]iodoantipyrine method in four structures of the whisker-to-barrel cortex pathway and in 18 structures unrelated to the pathway. Glibenclamide tended to lower baseline CBF in almost all regions examined, statistically significantly (P<0.05) in the cerebellar lobules with all doses, in the cerebellar cortex with 10 micromol/l, in the pontine nuclei with 2 and 10 micromol/l, and in the spinal trigeminal nucleus of the unstimulated side with all doses. Vibrissal stimulation increased CBF unilaterally in all the stations of the pathway, but the percent increases were not statistically significantly affected by the glibenclamide treatment, except in the spinal trigeminal nucleus where it was reduced statistically significantly (P<0.05) only by 2 micromol/l glibenclamide. These results indicate that K(ATP) channels may play a role in the tonic regulation of baseline CBF in some regions but provide no support for their role in the increases in CBF evoked by functional activation.

Afferent Pathways↗

Low lipoprotein lipase mass in preheparin serum of type 2 diabetes mellitus patients and its recovery with insulin therapy.

There exists lipoprotein lipase mass in preheparin serum, even though the activity is scarcely found. We studied the preheparin serum lipoprotein lipase mass levels (prehaparin LPL mass) in type 2 diabetes mellitus patients and the effect of insulin therapy on the levels of preheparin LPL mass. In 40 type 2 diabetes mellitus patients, preheparin LPL mass were measured by the sandwich enzyme-linked immunosorbent assay (ELISA), and were compared with those of non-diabetic healthy control. The correlation between preheparin LPL mass and Hemoglobin A(1c) (HbA(1c)), serum lipids were studied. Preheparin LPL mass were measured before and after insulin therapy. Preheparin LPL mass of type 2 diabetes mellitus patients was significantly lower than that of non-diabetic healthy control. In diabetic patients, preheparin LPL mass were negatively correlated with HbA(1c). Fifteen patients started to take insulin therapy. Preheparin LPL mass increased significantly at 4th week, when fasting blood glucose decreased. These results suggested that preheparin LPL mass was greatly regulated by insulin action.

Adult↗

Depot-specific expression of fibroblast growth factors in human adipose tissue.

OBJECTIVE: We have investigated the expression of several fibroblast growth factors (FGFs) and FGF-receptors (FGFRs) in human adipose tissue and adipose-tissue cell fractions obtained from both subcutaneous (sc) and omental (om) depots. RESEARCH METHODS AND PROCEDURES: Adipose tissue (sc and om) was obtained from obese men. Gene expression was analyzed by DNA microarrays in triplicate (n = 6) or by real-time polymerase chain reaction (n = 9). RESULTS: FGF-1, FGF-2, FGF-7, FGF-9, FGF-10, and FGF-18 transcripts were detected in human adipose tissue. The expression of FGF-2, FGF-7, and FGF-10 was similar in sc and om adipose tissue, whereas FGF-1 and FGF-9 were expressed at higher levels in the om adipose tissue. Expression of FGF-18 was only detected in om adipose tissue in two of the subjects. Analysis of cell fractions revealed that FGF-2 was only expressed in adipocytes; FGF-7, FGF-9, and FGF-18 were expressed in the stroma-vascular fraction; and FGF-1 and FGF-10 were expressed in both adipocytes and in the stroma-vascular fraction. FGFR-1 was expressed in both depots in all subjects and in both cell fractions, whereas FGFR-2 expression was undetectable in whole adipose tissue but detectable in the adipocyte fractions from both sc and om depots. DISCUSSION: We show that several members of the FGF family are expressed in human adipose tissue, and that the expression for some of the FGFs differs between sc and om adipose tissue. Taken together with previously published reports on the biological effects of FGFs on adipose cells, our results suggest that locally expressed FGFs could play role in the regulation of regional adipose tissue mass.

Adipocytes↗

Effects of dopamine receptor blockade on cerebral blood flow response to somatosensory stimulation in the unanesthetized rat.

Local cerebral blood flow (CBF) was determined in 30 cerebral structures, including four structures of the whisker-to-barrel cortex sensory pathway, by the quantitative autoradiographic [(14)C]iodoantipyrine method during unilateral vibrissal stimulation in rats administered 0.1 or 1.0 mg/kg haloperidol or its control vehicle intravenously. The low dose of haloperidol had no significant effects on resting CBF or its enhancement by vibrissal stimulation. By standard t tests, the high dose statistically significantly lowered baseline CBF in frontal and visual cortex, hippocampus, dentate gyrus, inferior olive, cerebellar cortex, and the ventral posteromedial (VPM) thalamic nucleus on the unstimulated side, and raised baseline CBF in the lateral habenula; however, these changes lost statistical significance after Bonferroni correction for multiple comparisons. Neither dose had any effects on the increases in CBF evoked by vibrissal stimulation in the principal sensory trigeminal nucleus and barrel cortex, but the higher dose statistically significantly enhanced the percent increases in CBF due to the sensory stimulation in the spinal trigeminal nucleus and VPM thalamic nucleus. These results do not support a role for direct dopaminergic vasoactive mechanisms in the increases in CBF associated with neuronal functional activation.

Animals↗