Transcytosis within PVN capillaries: a mechanism determining both hypertension-induced blood-brain barrier dysfunction and exercise-induced correction.

Although hypertension disrupts the blood-brain barrier (BBB) integrity within the paraventricular nucleus of hypothalamus (PVN) and increases the leakage into the brain parenchyma, exercise training (T) was shown to correct it. Since there is scarce and contradictory information on the mechanism(s) determining hypertension-induced BBB deficit and nothing is known about T-induced improvement, we sought to evaluate the paracellular and transcellular transport across the BBB within the PVN in both conditions. Spontaneously hypertensive rats (SHR) and WKY submitted to 4-wk aerobic T or sedentary (S) protocol were chronically catheterized for hemodynamic recordings at rest and intra-arterial administration of dyes (Rhodamine-dextran 70 kDa + FITC-dextran 10 kDa). Brains were harvesting for FITC leakage examination, qPCR evaluation of different BBB constituents and protein expression of caveolin-1 and claudin-5, the main markers of transcytosis and paracellular transport, respectively. Hypertension was characterized by increased arterial pressure and heart rate, augmented sympathetic modulation of heart and vessels, and reduced cardiac parasympathetic control, marked FITC extravasation into the PVN which was accompanied by increased caveolin-1 gene and protein expression, without changes in claudin-5 and others tight junctions' components. SHR-T vs. SHR-S showed a partial pressure reduction, resting bradycardia, improvement of autonomic control of the circulation simultaneously with correction of both FITC leakage and caveolin-1 expression; there was a significant increase in claudin-5 expression. Caveolin-1 content was strongly correlated with improved autonomic control after exercise. Data indicated that within the PVN the transcytosis is the main mechanism governing both hypertension-induced BBB leakage, as well as the exercise-induced correction.

Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation.

BACKGROUND: The role of the endothelial cell (EC) in blood flow regulation within the central nervous system has been little studied. Here, we explored EC participation in morphological changes of the anterior hypothalamic paraventricular nucleus (PVN) microvasculature of female rats at two reproductive stages with different metabolic demand (virginity and lactation). We measured the inner capillary diameter (ICD) of 800 capillaries from either the magnocellular or parvocellular regions. The space occupied by neural (somas, dendrites and axons) and glial, but excluding vascular elements of the neurovascular compartment was also measured in 100-µm2 sample fields of both PVN subdivisions. RESULTS: The PVN of both groups of animals showed ICDs that ranged from 3 to 10 microns. The virgin group presented mostly capillaries with small ICD, whereas the lactating females exhibited a significant increment in the percentage of capillaries with larger ICD. The space occupied by the neural and glial elements of the neurovascular compartment did not show changes with lactation. CONCLUSIONS: Our findings suggest that during lactation the microvasculature of the PVN of female rats undergoes dynamic, transitory changes in blood flow as represented by an increment in the ICD through a self-cytoplasmic volume modification reflected by EC changes. A model of this process is proposed.

The vasculature within the paraventricular nucleus of the hypothalamus in mice varies as a function of development, subnuclear location, and GABA signaling.

The paraventricular nucleus of the hypothalamus (PVN) is a cell group that plays important roles in regulating sympathetic vasomotor tone, food intake, neuroendocrine and autonomic stress responses, and cardiovascular function. The developing PVN is surrounded by neuronal elements containing, and presumably secreting, gamma-aminobutyric acid (GABA). The vasculature of the adult PVN is notably denser than in other brain regions or in the PVN during perinatal development. To characterize the postnatal angiogenic process in mice, blood vessels were analyzed at P8, 20, and 50 in rostral, mid, and caudal divisions of the PVN in males and females. Vascular changes relative to disruption of the R1 subunit of the GABA(B) receptor were evaluated at P8 and P20. For defined regions of interest within the PVN there were age dependent increases in blood vessel lengths and branching from P8 to 20 to 50 with the most notable increases in the middle region. Loss of GABA(B) receptors did not influence vascular characteristics at P8 in any region, but by P20 there was significantly (20%) less blood vessel length and branching in the mid-PVN region vs. wild type. These findings suggest that the loss of GABA(B) signaling may lead to a late developing defect in angiogenesis. The loss of vascularity with defective GABA(B) signaling suggests that neurovascular relationships in the PVN may be an important locus for understanding disorders of the hypothalamic-pituitary-adrenal axis with potential impact for psychiatric mood disorders along with other comorbid disorders that may be regulated by cells in the PVN.

EP3 receptors mediate PGE2-induced hypothalamic paraventricular nucleus excitation and sympathetic activation.

Prostaglandin E(2) (PGE(2)), an important mediator of the inflammatory response, acts centrally to elicit sympathetic excitation. PGE(2) acts on at least four E-class prostanoid (EP) receptors known as EP(1), EP(2), EP(3), and EP(4). Since PGE(2) production within the brain is ubiquitous, the different functions of PGE(2) depend on the expression of these prostanoid receptors in specific brain areas. The type(s) and location(s) of the EP receptors that mediate sympathetic responses to central PGE(2) remain unknown. We examined this question using PGE(2), the relatively selective EP receptor agonists misoprostol and sulprostone, and the available selective antagonists for EP(1), EP(3), and EP(4). In urethane-anesthetized rats, intracerebroventricular (ICV) administration of PGE(2), sulprostone or misoprostol increased renal sympathetic nerve activity, blood pressure, and heart rate. These responses were significantly reduced by ICV pretreatment with the EP(3) receptor antagonist; the EP(1) and EP(4) receptor antagonists had little or no effect. ICV PGE(2) or misoprostol increased the discharge of neurons in the hypothalamic paraventricular nucleus (PVN). ICV misoprostol increased the c-Fos immunoreactivity of PVN neurons, an effect that was substantially reduced by the EP(3) receptor antagonist. Real-time PCR detected EP(3) receptor mRNA in PVN, and immunohistochemical studies revealed sparsely distributed EP(3) receptors localized in GABAergic terminals and on a few PVN neurons. Direct bilateral PVN microinjections of PGE(2) or sulprostone elicited sympathoexcitatory responses that were significantly reduced by the EP(3) receptor antagonist. These data suggest that EP(3) receptors mediate the central excitatory effects of PGE(2) on PVN neurons and sympathetic discharge.

Adrenergic nerves mediate the venoconstrictor response to PVN stimulation.

Veins play an important role in the control of venous return, cardiac output and cardiovascular homeostasis. However, the central nervous system sites and effector systems involved in modulating venous function remain to be fully elucidated. The hypothalamic paraventricular nucleus (PVN) is an important site modulating autonomic outflow to the cardiovascular system. Venous tone can be modulated by sympathetic nerves or by adrenal catecholamines. The present study assessed the relative contribution of these autonomic effector systems to the venoconstrictor response elicited by stimulation of the hypothalamic paraventricular nucleus. Male Sprague-Dawley rats were subjected to sham operation or bilateral adrenal demedullation fitted with PVN guide cannulae and fitted with catheters for recording arterial pressure (AP) and intrathoracic vena caval pressure (VP). A latex balloon was advanced into the right atrium. MCFP was calculated from the AP and VP recorded after 4 s of right atrial occlusion. MCFP = VP + (AP - VP)/60. Mean arterial pressure (MAP), heart rate (HR), VP and MCFP responses to injections of BMI (25 ng/side) into the PVN were recorded from conscious rats to avoid the complicating effects of anesthesia. In sham-operated rats, injection of BMI into the PVN increased MAP by 13 +/- 3 mm Hg and HR by 56 +/- 6 bpm. MCFP was also increased significantly by 0.98 +/- 0.15 mm Hg indicating an increase in venomotor tone. Adrenal medullectomy did not affect the pressor (DeltaMAP = 12 +/- 2 mm Hg), tachycardic (DeltaHR = 48 +/- 7 bpm) or venoconstrictor (DeltaMCFP = 0.73 +/- 0.11 mm Hg) responses. Ganglionic blockade abolished the PVN-induced responses in both groups of rats. In a separate group, pretreatment with the adrenergic neuron blocker, guanethidine (20 mg/kg), also abolished the PVN-mediated venoconstrictor responses. Conversely, selective beta2 adrenergic receptor blockade did not affect MCFP responses to BMI. These data indicate that adrenomedullary catecholamines are not necessary for full expression of the venoconstrictor response to PVN stimulation.

Metabolic indices shift in the hypothalamic-neurohypophysial system during lactation: implications for interpreting their relationship with neuronal activity.

Metabolic indices of neuronal activity are thought to predict changes in the frequency of action potentials. There are stimuli that do not shift action potential frequency but change the temporal organization of neuronal firing following modifications of excitatory inputs by inhibitory synaptic activation. To our knowledge it is unknown whether this kind of stimulus associates with adjustments of metabolic markers of neuronal activity. Here, we used the hypothalamic-neurohypophysial system of lactating rats to address whether shifts in the temporal organization of neuronal firing relate with modifications of metabolic markers of neuronal activity. Cytochrome oxidase activity, (3)H-2-deoxyglucose uptake, and the area occupied by blood vessels increased in the paraventricular nucleus and neurohypophysis of lactating rats, as compared with their virgin counterparts. Taken together, these results suggest that metabolic demands denote shifts in the temporal organization of action potentials related with the adjustment of excitatory synaptic activation, and support that changes in metabolic markers do not necessarily reflect shifts in the frequency of action potentials.

Subcortical aphasia: three different language disorder syndromes?

The study analyses clinical presentation of language functions of 32 patients with subcortical aphasia induced by stroke. The patients have been divided into three groups according to neuroanatomic localization of the lesion, defined by CT and MRI examination (striato-capsular aphasia, aphasia associated with white matter paraventricular lesions and thalamic aphasia). The following batteries and tests were used: the neurologic examination, CT scan, MRI, Doppler ultrasound, Mini Mental State Examination, Boston Diagnostic Aphasia Examination (BDAE), Boston Naming Test (BNT), Token Test and Verbal Fluency Test. Clinical presentation of subcortical aphasias is characterized with preserved repetition, however, some groups differ by certain specific features of language impairment. Striato-capsular aphasia and aphasia associated with white matter paraventricular lesions are characterized with lack of speech fluency, occurrence of literary paraphasias, mainly preserved comprehension and naming. Thalamic aphasia, however, is characterized with fluent output, impaired comprehension and naming with predominant verbal paraphasias. The specific features of language impairment suggest that subcortical structures contribute to language organization. Considering the results of language tests we presume that the most prominent feature in striato-capsular aphasia is phonetic impairment of language, opposite to thalamic aphasia where lexical-sematic processing seems to be affected.

Endothelial activation is an intermediate step for peripheral lipopolysaccharide induced activation of paraventricular nucleus.

Peripheral injection of bacterial endotoxin lipopolysaccharide (LPS) activates the paraventricular nuclei of the hypothalamus (PVN), and consequently the hypothalamus-pituitary adrenal axis. Inflammatory cytokine interleukin-1 (IL-1) has been considered as a key mediator that translates the peripheral LPS stimulation into neuronal activation in the PVN. Several studies attempting to localize the expression of receptors for IL-1 (IL-1R), however, have failed to detect IL-1R on PVN neurons. It remains unclear, therefore, how IL-1 might stimulate the neurons of the PVN. In this study, we traced the cellular responsiveness to IL-1 by measuring the mRNA production of the cytokine responsive gene IkappaBalpha in the PVN. After either peripheral injection LPS or intracerebroventricular (i.c.v.) injection of IL-1beta, IkappaBalpha mRNA was found mostly in endothelial cells of the brain with the highest level of expression in PVN blood vessels. In addition, both injections also induced the expression of cyclooxygenase-2 in brain endothelial cells. Pretreatment with indomethacin, a cyclooxygenase inhibitor, blocked LPS and IL-1 induced neuronal activation in the PVN, but did not reduce the induction of IkappaBalpha in PVN endothelium. These results show that IL-1 acting on the endothelial cells of the brain, particularly in the PVN, may be an intermediate step relating peripheral immune signals to the brain.

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.

Ultrastructural localisation of ATP-gated P2X2 receptor immunoreactivity in vascular endothelial cells in rat brain.

In this report, we show for the first time that P2X2 receptors--ATP-gated cation channels--can be demonstrated in endothelial cells of small cerebral vessels of rat. Immunoreactivity to P2X2 receptors was visualised at the ultrastructural level with electron-immunocytochemistry (ExtrAvidin-horseradish peroxidase technique) using a polyclonal antibody against the fragment of an intracellular domain of the receptor. The possibilities that these receptors may regulate the formation of gap and/or tight junctions between adjacent endothelial cells influencing the blood-brain barrier, or modulate the contractility of capillary endothelial cells are discussed.

Galanin immunoreactivity in mouse basal forebrain: sex differences and discrete projections of galanin-containing cells beyond the blood-brain barrier.

The distribution of galanin-immunoreactive (GAL-IR) cell bodies in the basal forebrain of mice was investigated. The overall pattern of staining for GAL in the area of brain analyzed was similar to that reported in other species with noticeable variations. Distinctive groups of GAL-IR cells were present in the bed nucleus of stria terminalis (BNST), supraoptic nucleus, retrochiasmatic supraoptic nucleus (SOR), magnocellular paraventricular nucleus, arcuate nucleus (ARC) and the nucleus circularis which is one of the cell groups belonging to the accessory magnocellular system. Comparison of the number of GAL-IR cells between the sexes indicated sexual dimorphism in the BNST, SOR and the ARC. As compared with female mice, the mean number of GAL-IR cells/section in the BNST and the SOR was higher and that in the ARC was lower in the males. Unlike in rats, the preoptic area contained mostly scattered GAL-IR cell bodies. Intraperitoneal injection of the retrograde tracer fluoro-gold in male mice resulted in uptake of fluoro-gold by selective GAL-IR cell groups in the basal forebrain suggesting that only some of these cell groups may project outside the blood-brain barrier whereas others may be involved in intracerebral neural transmission.

Hypothalamic accessory nuclei and their relation to the angiotensinergic and vasopressinergic systems.

The existence and colocalization of angiotensin II- and vasopressin-like immunoreactivity in individual magnocellular cell groups of the hypothalamus has been demonstrated by using immunocytochemical methods. These neurosecretory magnocellular groups consist of the paraventricular nucleus and the supraoptic nucleus, as well as different accessory cell groups. The fibers from the neurons of the accessory nuclei project directly to adjacent blood vessels and do not comigrate with the hypothalamo-neurohypophysial fiber pathway. On the basis of these findings it can be concluded that in the hypothalamus two different angiotensinergic and vasopressinergic neurosecretory systems exist: (1) an intrinsic hypothalamic and (2) a hypothalamo-neurohypophysial system. The distribution of the accessory cell groups in the hypothalamus is shown in a 3D reconstruction which includes the connection of these magnocellular nuclei with the vascular system in this area.

Volume expansion fails to normally activate neural pathways in the brain of conscious rabbits with heart failure.

Immunohistochemical detection of the protein, Fos, was used to identify neurons in the brain activated following a volume load in conscious rabbits with doxorubicin-induced congestive cardiomyopathy. The plasma expander, Haemaccel, was infused intravenously into rabbits for 60 min and significantly increased right atrial pressure, blood pressure and heart rate. The rabbits were perfusion fixed 90 min after the start of the infusion and the distribution of Fos-positive cell nuclei was examined. Compared to control rabbits with heart failure, there was a small significant increase in the number of Fos-positive cell nuclei in the organum vasculosum of the lamina terminalis following volume expansion. In other regions of the brain that were studied in detail, there were no significant increases in Fos production. These included the parvocellular paraventricular nucleus (PVN) of the hypothalamus, the midbrain periaqueductal gray, the nucleus tractus solitarius (NTS), area postrema and the ventrolateral medulla (VLM). In the supraoptic nucleus and the magnocellular PVN, no Fos-positive cell nuclei were present as expected. The median preoptic nucleus, the bed nucleus of the striae terminalis and the diagonal band of Broca contained some Fos but there was no marked difference between volume expanded and control animals. In the anterior cortical and medial subnuclei of the amygdala there was a high concentration of Fos but there was no consistent difference between the two groups. The present findings in heart failure rabbits suggest that most brain regions are not activated sufficiently by the stimulus to elicit Fos expression. The results are in accord with findings showing that sympathetic reflexes initiated by volume expansion are attenuated in heart failure.

Disinhibition of the hypothalamic paraventricular nucleus increases mean circulatory filling pressure in conscious rats.

Venous capacitance plays an important role in the control of cardiac output. However, the central nervous system sites and neurochemical signals involved in modulating venous function remain to be fully elucidated. The hypothalamic paraventricular nucleus (PVN) is an important site modulating autonomic outflow to the cardiovascular system. The present study tested the hypothesis that removal of tonic GABAergic tone in the PVN would increase peripheral venous tone. Mean circulatory filling pressure was used as an index of venous tone. Arterial pressure, venous pressure, heart rate, and mean circulatory filling pressure (MCFP) were monitored in conscious male Sprague Dawley rats. The rats were challenged with microinjections of bicuculline methiodide (BMI) (25 ng) or vehicle (artificial cerebrospinal fluid) into the PVN. In one group of rats, BMI injections were performed before and after ganglionic blockade with chlorisondamine hydrochloride (10 mg/kg) and atropine (0.4 mg/kg) given subcutaneously. In a second group, BMI injections were performed in chlorisondamine-treated rats whose blood pressure had been returned to control with an infusion of norepinephrine. Injection of bicuculline into the PVN increased MAP (14 +/- 2 to 18 +/- 2 mmHg) and HR (49 +/- 12 to 74 +/- 14 bpm). MCFP also increased significantly by 1.00 +/- 0.17 to 1.39 +/- 0.18 mmHg, indicating an increase in the driving pressure for venous return. Injection of the vehicle did not affect these variables. In both groups, ganglionic blockade significantly attenuated the bicuculline-induced increases in MAP, HR and MCFP. These data indicate that sympathetic drive from the PVN to the venous system is under tonic GABAergic control.

The hypothalamic paraventricular nucleus in two types of Wistar rats with different stress responses. I. Morphometric comparison.

The present study evaluates the role of the hypothalamic paraventricular nucleus (PVH) in stress regulation by a morphometric comparison of the vascular, neuronal and synaptic properties of this nucleus in two lines of Wistar rats. It has been previously reported that these two lines of rats, indicated as APO-SUS (apomorphine-susceptible) and APO-UNSUS (apomorphine-unsusceptible) rats on the basis of their reactivity to a subcutaneous injection of apomorphine, display a variety of pharmacological and behavioral differences, including differences in their stress-coping mechanisms (Cools et al., Neuropsychobiology, 28 (1993) 100-105). The results show a similar vascular and neuronal organization of the PVH in both lines, but distinct synaptic differences. The PVH (0.12 mm3 volume with about 15,000 neurons on one side) has an overall vascular density of 5.6%, with significant differences between subdivisions (parvocellular central part: 8.3%, parvocellular dorsal/ventral/posterior part: 4.6-5.3%), which means that vascularity is a useful tool to delineate subdivisions in the parvocellular PVH. The neuronal density of 132 x 10(3)/mm3 as found in the present study is two times higher than reported in a previous study Possible reasons for this discrepancy are extensively discussed. The most significant finding of the present study is the observation that APO-SUS rats have a significantly higher synaptic density (158 x 10(6)/mm3) in the PVH than APO-UNSUS rats (108 x 10(6)/mm3). It is discussed in which way this synaptic difference may be correlated with the different activity of the hypothalamo-pituitary-adrenal axis in both lines of Wistar rats.

Microvascular density of the human paraventricular nucleus decreases with aging but not hypertension.

Microvascular density was determined in the supraoptic nuclei (SON) and paraventricular nuclei (PVN) of fixed brain tissue from 19 human subjects ranging in age from 30 to 85 years. Eight of these patients had hypertension. No sex- or hypertension-related differences in microvascular density were found in either the SON or PVN. However, capillary density decreased in the PVN with aging. These results indicate a differential pattern of microvascular loss in the human hypothalamus with aging.

Ultrastructure of hypothalamic paraventricular neurons.

The hypothalamic paraventricular nucleus (PVN) plays a pivotal role in the regulation of endocrine processes and the modulation of autonomic functions. The multi-channel outputs of the nucleus are directed toward the anterior and posterior lobes of the pituitary, autonomic centers, and limbic structures. Counterbalancing the wide spectrum of efferent projections, the nucleus receives humoral signals from endocrine glands and neuronal afferents from several loci of the brain. The multiple functions of the nucleus are executed by neurons that are organized in distinct subnuclei and display complex chemotypes. The review demonstrates and discusses the organization, architecture, chemical composition, plasticity, and pathology of paraventricular neurons of the rat hypothalamus from the perspective of ultrastructural analysis. Electron microscopy--by its high resolution--offers a powerful tool that is suitable for revealing the structural background of physiological processes that modulate and govern the operation of paraventricular neurons.

Noradrenergic innervation of the hypothalamus of rhesus monkeys: distribution of dopamine-beta-hydroxylase immunoreactive fibers and quantitative analysis of varicosities in the paraventricular nucleus.

The distribution of noradrenergic processes within the hypothalamus of rhesus monkeys (Macaca mulatta) was examined by immunohistochemistry with an antibody against dopamine-beta-hydroxylase. The results revealed that the pattern of dopamine-beta-hydroxylase immunoreactivity varied systematically throughout the rhesus monkey hypothalamus. Extremely high densities of dopamine-beta-hydroxylase-immunoreactive processes were observed in the paraventricular and supraoptic nuclei, while relatively lower levels were found in the arcuate and dorsomedial nuclei and in the medial preoptic, perifornical, and suprachiasmatic areas. Moderate levels of dopamine-beta-hydroxylase immunoreactivity were found throughout the lateral hypothalamic area and in the internal lamina of the median eminence. Very few immunoreactive processes were found in the ventromedial nucleus or in the mammillary complex. Other midline diencephalic structures were found to have high densities of dopamine-beta-hydroxylase immunoreactivity, including the paraventricular nucleus of the thalamus and a discrete subregion of nucleus reuniens, the magnocellular subfascicular nucleus. A moderate density of dopamine-beta-hydroxylase immunoreactive processes were found in the rhomboid nucleus and zona incerta whereas little dopamine-beta-hydroxylase immunoreactivity was found in the fields of Forel, nucleus reuniens, or subthalamic nucleus. The differential distribution of dopamine-beta-hydroxylase-immunoreactive processes may reflect a potential role of norepinephrine as a regulator of a variety of functions associated with the nuclei that are most heavily innervated, e.g., neuroendocrine release from the paraventricular and supraoptic nuclei, and gonadotropin release from the medial preoptic area and mediobasal hypothalamus. Additionally, quantitative analysis of dopamine-beta-hydroxylase-immunoreactive varicosities was performed on a laser scanning microscope in both magnocellular and parvicellular regions of the paraventricular nucleus of the hypothalamus. The methodology employed in this study allowed for the high resolution of immunoreactive profiles through the volume of tissue being analyzed, and was more accurate than conventional light microscopy in terms of varicosity quantification. Quantitatively, a significant difference in the density of dopamine-beta-hydroxylase-immunoreactive varicosities was found between magnocellular and parvicellular regions, suggesting that parvicellular neurons received a denser noradrenergic input. These differential patterns may reflect an important functional role for norepinephrine in the regulation of anterior pituitary secretion through the hypothalamic-pituitary-adrenal stress axis.

Vasopressinergic neurons and the associated blood vessels in the rat anterior hypothalamus: an immunohistochemical study.

The paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamic neurosecretory system have been extensively investigated by many workers. The functional aspects of vasopressin secretion (elaborated by the PVN and SON neurons) in relation to the vasculature of the anterior hypothalamus are also well documented. However, the available data concerning vasopressin (VP) functions are largely based on physiological studies. Corroborative morphological correlation with regard to this has received little attention. The present report elucidates the intricate anatomical relationships between the VP-neurons and the adjoining capillaries in the rat anterior hypothalamus. A peroxidase-antiperoxidase (PAP) immunocytochemical study, using a commercial VP antibody, was carried out for this purpose. The observations are interpreted from a functional standpoint. VP-immunostained elements, i.e. the somata and the processes (mainly dendrites), were localized (i) close to the wall, (ii) on the endothelium, and (iii) occasionally, in the lumen of the hypothalamic capillaries. The findings provide immunocytochemical evidence that the vasopressinergic elements are in direct relationship with the hypothalamic vasculature. This raises some interesting possibilities for the former to be involved in: (i) affecting the permeability of the blood-brain barrier for transport of various nutrient substances (important in aging and Alzheimer's disease), (ii) inducing an alteration in the water permeability of the brain vessels on which depends the precise adjustment of brain water content and of brain volume (fundamental to normal functioning of the brain), and (iii) serving as osmoreceptors of the blood flowing through the capillaries and thus providing a feedback mechanism for VP modulation.