Continuous cytosine-b-D-arabinofuranoside infusion reduces ectopic granule cells in adult rat hippocampus with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus

Brief or prolonged seizures induce various patterns of plasticity. Axonal or dendritic remodelling and development of ectopic granule cells have been described in the hilus and molecular layer of the adult rodent hippocampus. Hippocampal cell proliferation also occurs after seizures. However, whether the seizure-induced cell proliferation plays a pathological or reparative role in the epileptic brain is unknown. In this study, we attempted to suppress the seizure-induced cell proliferation with the antimitotic agent cytosine-b-D-arabinofuranoside (Ara-C) and to examine the development of spontaneous recurrent seizures (SRS). Experimental status epilepticus was induced with pilocarpine, and Ara-C or vehicle alone was infused continuously with an osmotic minipump. SRS were video-monitored. BrdU immunohistochemistry was used for the spatial and temporal analysis of hippocampal cell proliferation, and double labelling with NeuN, calbindin and GFAP antibodies was performed for the differentiation of BrdU-positive cells. Timm staining was also performed for evaluation of mossy fibre sprouting (MFS). With continuous Ara-C infusion, the likelihood of developing SRS was decreased and, during the latent period, the development of ectopic granule cells in the hilus and new glia in the CA1 area was reduced when compared with the vehicle-infused group, while MFS was not altered. The results suggest that the hippocampal cell proliferation plays a pro-epileptogenic role rather than a compensatory role, and that the epileptogenic process may be associated with the generation of new glia in the CA1 area and/or new neurons in the dentate gyrus, particularly the ectopically located hilar granule cells.     

Transient reduction of cerebral blood flow leads to longlasting increase in GABA content in vulnerable structures and decreased susceptibility to bicuculline induced seizures

Summary Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. The GABA content was measured 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. In other groups of rats seizures were elicited by i.p. injection of (+)-bicuculline (3 mg/kg) 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. Analysis of the GABA content revealed significant increase compared with controls in the hippocampus, frontal cortex and substantia nigra from 24 hours up to 3 months. Bicuculline treatment induced tonic/clonic seizures and status epilepticus in sham operated animals; these effects were drastically diminished at various time points after BCCA. The present results suggest that BCCA produces a longlasting increase in GABA content and as a consequence protection from bicuculline-induced seizures.     

Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine

Sustained, generalized seizure activity was induced in anaesthetized (70% N2O), paralyzed and artifically ventilated rats by i.p. DL-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD+ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations. Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occurring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine. Cerebral blood flow (CBF) and oxygen utilization (CMRO2) were measured during sustained seizures. CMRO2 rose to 150% of control, with a corresponding increase in CBF.     

Risk and predictors of early epileptic seizures in acute cerebral venous and sinus thrombosis

We assessed the risk and determined predictors of early epileptic seizures (ES) in patients with acute cerebral venous and sinus thrombosis (CVST). A prospective series of 194 consecutive patients with acute CVST admitted to neurological wards in two German university hospitals was analysed for frequency of ES and in-hospital mortality. Demographic, clinical and radiological characteristics during the acute stage were retrospectively analysed for significant association with ES in univariate and multivariate analyses. During the acute stage, 19 patients (9.8%) died. Early symptomatic seizures were found in 86 patients (44.3%). Status epilepticus occurred in 11 patients (12.8%) of whom four died. Amongst patients with epileptic seizures, mortality was three times higher in those with status than in those without (36.4% and 12%, respectively). In multivariate logistic regression analysis, motor deficit [odds ratio (OR) 5.8; 95% CI 2.98–11.42; P  < 0.001], intracranial haemorrhage (OR 2.8; 95% CI 1.46–5.56; P  = 0.002) and cortical vein thrombosis (OR 2.9; 95% CI 1.43–5.96; P  = 0.003) were independent predictors of early epileptic seizures. Status epilepticus was an important source of morbidity and early mortality in patients with CVST in this study. Patients with focal motor deficits, cortical vein thrombosis and intracranial haemorrhage carried the highest risk for ES. Prophylactic antiepileptic treatment may be an option for these patients.     

Local tissue oxygen tension - cytochrome a,a3 redox relationships in rat cerebral cortex in vivo

Simultaneous measurements were made from rat cerebral cortex, in situ, of focal changes in both tissue oxygen tension (ptO2) and the reduction/oxidation ratio of cytochrome c oxidase (cytochrome a,a3) in order to study relationships between oxygen supply and consumption in small regions of tissue. Local ptO2 was measured with polarographic microelectrodes and the redox state of cytochrome a,a3 with a dual wavelength reflectance spectrophotometer. Increased ptO2, produced by respiration of gas mixtures with elevated O2 and/or CO2 content, was accompanied by increased oxidation of cytochrome a,a3. This confirms that cytochrome oxidase is not fully oxidized in focal brain tissue regions in vivo, as it is in mitochondria isolated in vitro. Decreased ptO2 was accompanied by cytochrome a,a3 reduction. The oxidative changes of cytochrome a,a3 with increases in ptO2 were smaller than the reductive changes associated with decreases in ptO2. Curves relating cytochrome a,a3 redox state to ptO2 were qualitatively alike, regardless of the initial ptO2 value from which they were generated. Thus, the reduction level of cytochrome a,a3 varied with ptO2 on a continuum. This consistent relationship demonstrates that changes in mitochondrial redox state provide an index of relative changes in tissue oxygenation in intact neocortex. The results suggest also that local rates of cerebral oxidative metabolism may not always be constant with changes in local ptO2.     

Cerebral metabolic and circulatory changes in the rat during sustained seizures induced bydl-homocysteine

Sustained, generalized seizure activity was induced in anaesthetized (70%N₂O), paralyzed and artificially ventilated rats by i.p.dl-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD⁺ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations.Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occuring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine.Cerebral blood flow (CBF) and oxygen utilization (CMR_O2) were measured during sustained seizures. CMR_O2 rose to 150% of control, with a corresponding increase in CBF.     

Hypometabolism precedes limbic atrophy and spontaneous recurrent seizures in a rat model of TLE

Purpose: Temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG‐PET) is a common finding in patients with drug‐resistant temporal lobe epilepsy (TLE). The pathophysiology underlying the hypometabolism, including whether it reflects a primary epileptogenic process, or whether it occurs later as result of limbic atrophy or as a result of chronic seizures, remains unknown. This study aimed to investigate the ontologic relationship among limbic atrophy, histological changes, and hypometabolism in rats. Methods: Serial in vivo imaging with FDG‐PET and volumetric magnetic resonance imaging (MRI) was acquired before and during the process of limbic epileptogenesis resulting from kainic acid–induced status epilepticus in the rat. The imaging data were correlated with histologic measures of cell loss, and markers of astrogliosis (glial fibrillary acid protein [GFAP]), synaptogenesis (synaptophysin), glucose transporter 1 (Glut1) and energy metabolism (cytochrome oxidase C), on brains of the animals following the final imaging point. Key Findings: Hippocampal hypometabolism on FDG‐PET was found to be present 24 h following status epilepticus, tending to lessen by 1 week and then become more marked again following the onset of spontaneous seizures. Atrophy of limbic structures was evident from 7 days post‐SE, becoming progressively more marked on serial MRI over subsequent weeks. No relationship was observed between the severity of MRI‐detected atrophy or CA1 pyramidal cell loss and the degree of the hypometabolism on FDG‐PET. However, an inverse relationship was observed between hypometabolism and increased expression of the Glut1 and synaptophysin in the hippocampus. Significance: These findings demonstrate that hypometabolism occurs early in the processes of limbic epileptogenesis and is not merely a consequence of pyramidal cell loss or the progressive atrophy of limbic brain structures that follow. The hypometabolism may reflect cellular mechanisms occurring early during epileptogenesis in addition to any effects of the subsequent recurrent spontaneous seizures.     

Rat models of dementia based on reductions in regional glucose metabolism,cerebral blood flow and cytochrome oxidase activity

Summary. Three models are described in rats which attempt to mimic morphological and behavioural pathology of Alzheimers dementia; intracerebroventricular injection of streptozotocin (STZ), permanent bilateral carotid artery occlusion (2VO) and brain mitochondrial cytochrome oxidase inhibition by sodium azide. Learning and memory are impaired within 4 weeks in all models. This probably involves a reduction in cortical and/or hippocampal cholinergic neurotransmission. STZ causes microglial activation and specific damage to myelinated tracts in the fornix through generation of oxidative stress, thereby disrupting connections between the septum and hippocampus. 2VO results in damage to myelin and CA1 cells in hippocampus and in abnormal processing of APP to -amyloid. It is not known if microglial activation and neuronal damage occur after sodium azide administration. Memory and learning can be improved in the STZ and 2VO models by estradiol, melatonin and cholinesterase inhibitors. Antioxidants and neuroprotective agents may also decrease memory deficits by preventing inflammation and neurodegeneration.     

Hippocampal mitochondrial cytochrome C oxidase activity and gene expression in a rat model of chronic cerebral ischemia

The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria. Results showed significantly decreased cytochrome C oxidase activity and cytochrome C oxidase II mRNA expression with prolonged ischemia time. Further analysis re-vealed five mitochondrial cytochrome C oxidase II gene mutations, two newly generated mutations, and four absent mutational sites at 1 month after cerebral ischemia, as well as three mitochondrial cytochrome C oxidase III gene mutations, including two newly generating mutations, and one dis-appeared mutational site at 1 month after cerebral ischemia. Results demonstrated that decreased cytochrome C oxidase gene expression and mutations, as well as decreased cytochrome C oxidase activity, resulting in energy dysmetabolism, which has been shown to be involved in the pathological process of ischemic brain injury.     

Suction lesions of the frontal cerebral cortex in the rat induce asymmetrical behavioral and catecholaminergic responses

Suction lesions of the right frontal cerebral cortex in rats induce a period of spontaneous hyperactivity. This hyperactivity, as measured by an increase in running wheel activity begins about one week post-operatively and continues throughout the remainder of a 30-day observation period. The increased activity is accompanied by a bilateral decrease in norepinephrine concentrations in both the ipsilateral and contralateral cortex and locus coeruleus. Identical lesions of the left frontal cerebral cortex produce neither the hyperactivity nor a decrease in norepinephrine concentrations. These experiments have reproduced many of the behavioral and biochemical asymmetries seen after middle cerebral artery ligation; however, suction lesions are both simpler to produce and histologically less variable in their effects.     

Differences in some of the metabolic properties of mitochondrial isolated from cerebral cortex and olfactory bulb of the rat

The metabolic properties of mitochondria from rat cerebral cortex and olfactory bulb were investigated. The pyruvate-supported oxygen uptake rates by olfactory bulb mitochondria were significantly lower than those by cerebrocortical mitochondria. This is consistent with the differences in pyruvate dehydrogenase complex activities between these mitochondrial preparations. Pyruvate dehydrogenase kinase, NAD-linked isocitrate dehydrogenase, and hexokinase activities in olfactory bulb mitochondria were significantly lower than those in cerebrocortical mitochondria. However, NADP-linked isocitrate dehydrogenase, and NAD-linked and NADP-linked glutamate dehydrogenase activities in olfactory bulb mitochondria were significantly higher than those in cerebrocortical mitochondria. The differences between these two mitochondrial preparations in terms of the activities of these energy-metabolizing enzymes reflect the differences detected in the homogenates of these regions.     

Changes in midline thalamic recruiting responses in the prefrontal cortex of the rat during the development of chronic limbic seizures

Purpose:   Mesial temporal lobe epilepsy (MTLE) is a common form of epilepsy that affects the limbic system and is associated with decreases in memory and cognitive performance. The medial prefrontal cortex (PC) in rats, which has a role in memory, is associated with and linked anatomically to the limbic system, but it is unknown if and how MTLE affects the PC.
Methods:   We evoked responses in vivo in the PC by electrical stimulation of the mediodorsal (MD) and reuniens (RE) nuclei of the thalamus at several time points following status epilepticus, before and after onset of spontaneous seizures. Kindled animals were used as additional controls for the effect of seizures that were independent of epilepsy.
Results:   Epileptic animals had decreased response amplitudes and significantly reduced recruiting compared to controls, whereas kindled animals showed an increase in both measures. These changes were not associated with neuronal loss in the PC, although there was significant loss in both the MD and RE in the epileptic animals.
Conclusions:   There is a significant reduction in the thalamically induced evoked responses in the PCs of epileptic animals. This finding suggests that physiologic dysfunction in MTLE extends beyond primary limbic circuits into areas without overt neuronal injury.     

脑血管病患者医院感染状况及其相关因素的研究

目的 研究脑血管病患者医院感染状况及其相关因素.方法 对2108例脑血管病患者临床表现、实验室和影像学检查结果进行监测,统计、分析医院感染的发生率、死亡率、感染部位及其相关因素.结果 本组患者发生医院感染726例(34.4%).医院感染组死亡125例(17.2%),无医院感染组死亡112例(8.1%),两组差异有统计学意义(P＜0.01).医院感染发生部位以呼吸道(64.2%)和泌尿道(21.1%)最常见.高龄、住院时间长、脑出血、意识障碍、有侵入性治疗、高血糖及预防性使用抗生素的患者医院感染发生率显著高于年龄较轻、住院时间短、脑梗死、意识清楚、无侵入性治疗、血糖正常及未预防性使用抗生素的患者(均P＜0.01).结论 脑血管病患者医院感染的发生率高,感染患者的死亡率增高.高龄、住院时间长、脑出血、意识障碍、有侵入性治疗、高血糖和预防性使用抗生素是脑血管病患者并发医院感染的常见相关因素.     

Mapping of neuronal networks underlying generalized seizures induced by increasing doses of pentylenetetrazol in the immature and adult rat: a c‐Fos immunohistochemical study

Previous studies from our group have shown that pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to age-dependent acute and long-term metabolic and circulatory changes in immature rats. In order to define the neural substrates involved in PTZ seizures according to age, the purpose of the present study was to map the areas of cellular activation during seizures of increasing severity in 10-day-old (P10), 21-day-old (P21) and adult rats. Seizures were induced by repetitive injections of subconvulsive doses of PTZ. The total dose received by the animals ranged from 4 to 125 mg/kg. These doses induced a variety of seizure profiles including absence-like, clonic seizures and SE. The cellular activation was measured as the density of c-Fos immunoreactive cells in animals at 2 h after the onset of the seizures. In P10 rats receiving a behaviourally non-active dose of PTZ, c-Fos immunoreactivity appeared only in the amygdala. The dose of 40 mg/kg that induced absence-like seizures led to a weak c-Fos expression in the medial thalamus, some cortical areas and globus pallidus. Clonic seizures reinforced labelling in the previous areas and induced a spread of c-Fos immunoreactivity to other cortical areas, thalamus, hypothalamus and some brainstem nuclei. At that age, only SE led to a widespread and stronger expression of c-Fos which was, however, totally lacking in the midbrain, and remained incomplete in the brainstem and forebrain limbic system, including the hippocampus. In P21 and adult rats, the inactive dose of PTZ induced c-Fos immunoreactivity in thalamus and hypothalamus. With absence-like seizures, c-Fos labelling spread to the cerebral cortex, amygdala, septum and some brainstem regions. With clonic seizures, immunoreactivity was reinforced in all areas already activated by absence-like seizures, and appeared in the striatum, accumbens, brainstem and hippocampus, except in CA1. After SE, c-Fos was strongly expressed in all brain areas. The intensity of c-Fos labelling was higher in most regions of P21 compared to adult rats. These data are in agreement with the immaturity of cellular and synaptic connectivity in P10 rats, the known greater sensitivity of rats to various kinds of seizures during the third week of life and the nature of the neural substrates involved in PTZ seizures.     

Cytochrome oxidase activity of the suprachiasmatic nucleus and pineal gland in rats with portacaval shunt

Rhythmic behavioral and biochemical changes have been observed in both human and animal models with hepatic insufficiency. The basis of all these alterations is the principal endogenous pacemaker, the suprachiasmatic nucleus. The aim of this work, therefore, is to determine cytochrome c oxidase activity, a marker of neuronal activity and oxidative metabolism, in this nucleus in rats with portacaval shunt. In order to do this, this enzyme was histochemically marked and quantified by computer-assisted optical densitometry. Results show a reduced cytochrome oxidase activity in the suprachiasmatic nucleus in animals with portacaval shunts and, inversely, an increase in oxidative metabolism in the pineal gland, another circadian structure. However, the activity measured in a noncircadian brain structure, the hippocampus, which served as a control, showed no changes with surgery. Additionally, locomotor activity was assessed by actimeters and revealed a clearly reduced activity in animals with portacaval shunt. We conclude that the suprachiasmatic nucleus is possibly involved in the rhythmic changes associated with hepatic insufficiency.     

Effects of aging and glucocorticoid treatment on monoamine oxidase subtypes in rat cerebral cortex: Therapeutic implications

Dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis is more common in elderly depression than in younger cohorts, resulting in elevated glucocorticoid levels. Effectiveness of antidepressant drugs is also impaired in these patients. We evaluated the effects of continuous infusions of dexamethasone on monoamine oxidase (MAO) subtypes in aged rat brain to determine whether unique interactions of glucocorticoids and aging could contribute to abnormal transmitter disposition. Aged rats given dexamethasone showed robust induction of both MAO A (threefold increase) and B (30% increase) in the frontal/parietal cortex, effects in the opposite direction from those seen in young rats treated with glucocorticoids. Our results support the view that depression in the elderly may have biologically discrete components that make it differ from depression in younger people. These distinctions may influence the etiology and therapy of depression, while at the same time providing potential biomarkers (such as platelet MAO) that may serve to predict successful treatment outcome in patient subpopulations.     

Effect of aging on dopamine metabolism in the rat cerebral cortex: a regional analysis

Summary Age-related changes in the levels of dopamine (DA) and its metabolites were measured in seven cerebral cortical areas and in the striatum of 3, 10 and 27 month-old Sprague-Dawley rats. An age-related increase in DA levels was observed in the somatomotor (SM) cortex. In contrast, a decrease was observed in the temporal (T) cortex. Decreases in homovanillic acid (HVA) levels were observed in prelimbic (PL), pyriform (PY) and T cortex of aged rats, whereas significant increases in the levels of 3-methoxytyramine (3-MT) were observed in PL, prefrontal (PF), cingulate (C) as well as in T cortex. In the striatum, DA and HVA were decreased but the level of 3-MT remained unchanged. Norepinephrine (NE) levels increased in rats from 3 to 27 months in all the cortical areas. The increase in the levels of the DA extraneuronal metabolite, 3-MT, confirms our previous results showing that the release of DA might be increased with age in some cortical areas. The present results show that there is no general age-related decrease in the level of monoamines and of their metabolites in the rat cerebral cortex and that the changes display a complex, area-specific pattern.     

Distribution of catecholamines and serotonin in the rat cerebral cortex: Absolute levels and relative proportions

Summary The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine serotonin using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability.     

Time-course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6-hydroxydopamine in the rat: new clues from an old model

Despite the progressive development of innovative animal models for Parkinson's disease, the intracerebral infusion of neurotoxin 6-hydroxydopamine (6-OHDA) remains the most widely used means to induce an experimental lesion of the nigrostriatal pathway in the animal, due to its relatively low complexity and cost, coupled with the high reproducibility of the lesion obtained. To gain new information from such a classic model, we studied the time-course of the nigrostriatal damage, metabolic changes in the basal ganglia nuclei (cytochrome oxidase activity) and behavioural modifications (rotational response to apomorphine) following unilateral injection of 6-OHDA into the corpus striatum of rat, over a 4-week period. Striatal infusion of 6-OHDA caused early damage of dopaminergic terminals, followed by a slowly evolving loss of dopaminergic cell bodies in the substantia nigra pars compacta, which became apparent during the second week post-injection and peaked at the 28th day post-infusion; the rotational response to apomorphine was already present at the first time point considered (Day 1), and remained substantially stable throughout the 4-week period of observation. The evolution of the nigrostriatal lesion was accompanied by complex changes in the metabolic activity of the other basal ganglia nuclei investigated (substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and subthalamic nucleus), which led, ultimately, to a generalized, metabolic hyperactivity, ipsilaterally to the lesion. However, peculiar patterns of metabolic activation, or inhibition, characterized the post-lesional responses of each nucleus, in the early and intermediate phases, with peculiar response profiles that varied closely related to the functional position occupied within the basal ganglia circuitry.     

Hypervascularization in the magnocellular nuclei of the rat hypothalamus: relationship with the distribution of aquaporin-4 and markers of energy metabolism

In the magnocellular nuclei of the hypothalamus, there is a rich vascular network for which the function remains to be established. In the supraoptic nucleus, the high vascular density may be one element, which together with the water channel aquaporin-4 expressed in the astrocytes, is related to a role in osmoreception. We tested the osmoreception hypothesis by studying the correlation between vascular and cellular densities in the paraventricular nucleus and the supraoptic nucleus. Whether aquaporin-4 is likely to contribute to osmoreception was tested by studying the distribution in the magnocellular nuclei of the hypothalamus. The high vascular density may also reflect a high metabolic activity due to the synthesis of vasopressin and oxytocin. This metabolic hypothesis was tested by studying the regional cytochrome oxidase histochemistry, the local cerebral blood flow, and the density of glucose transporter type-1 in the supraoptic and paraventricular nuclei. All the magnocellular nuclei were characterized by an extended and intense aquaporin-4 labelling and a weak cytochrome oxidase histochemistry. The highest vascular density was found in the supraoptic nucleus and the magnocellular regions of the paraventricular nucleus. The local cerebral blood flow rates were surprisingly low in the paraventricular nucleus and the supraoptic nucleus in comparison to the cerebral cortex. Furthermore in these nuclei, the antibody for glucose transporter type-1 revealed two populations of vessels differing by their labelling intensity. The similarities observed between the different nuclei suggest that, in the hypothalamus, all magnocellular regions sense the plasma osmolarity. The low local cerebral blood flow, and the patterns of glucose transporter type-1 labelling and cytochrome oxidase histochemistry suggest that the high vascularization of these hypothalamic nuclei is not related to a high metabolic capacity in basal conditions.