Modulation of Hyperosmotic and Immune-Induced Disruption of the Blood-Brain Barrier by the Nitric Oxide System.

Objectives: The role of nitric oxide (NO) in modulating the blood-brain barrier (BBB) is not entirely clear. We examined the effect of different NO synthase (NOS) inhibitors and NO donors on the permeability of the BBB in animals with normally functioning brain blood vessels, following disruption by hyperosmotic mannitol and during immune inflammation.

Methods: We administered L-NAME, aminoguanidine, S-methyl-thiocitrulline (SMT) and 7-indazole (NOS inhibitors) and NOR-4 (an NO donor) into the cerebral ventricle of rats.

Electrical stimulation of the amygdala modifies the negative feedback effect of glucocorticoids on the adrenocortical responses to stress.

Objective: The amygdala (AMG) plays a facilitatory role in the hypothalamic-pituitary-adrenal (HPA) axis. The effect of the AMG on the negative feedback exerted by glucocorticoids (GC) is not clear. We investigated the effect of repeated electrical stimulation of the AMG on the feedback action of GC upon the adrenocortical (AC) response to stressful stimuli.

Delayed effects of brain irradiation--part 1: adrenocortical axis dysfunction and hippocampal damage in an adult rat model.

Background: Brain irradiation (BI) in humans may cause behavioral changes, cognitive impairment and neuroendocrine dysfunction. The effect of BI on the hypothalamic-pituitary-adrenal (HPA) axis is not fully understood.

Objectives: To evaluate the effect of BI on HPA axis responses under basal and stressful conditions as well as following pretreatment with dexamethasone (Dex).

Delayed central nervous system irradiation effects in rats--part 2: aggravation of experimental autoimmune encephalomyelitis.

Background: Central nervous system (CNS) irradiation has detrimental effects which become evident within hours to few days and after a long latency of months and years. However, the delayed effect of irradiation on neuroimmune diseases has not been thoroughly examined.

Objectives: We evaluated the delayed effects of irradiation on the course of experimental autoimmune encephalomyelitis (EAE), which is used as a model for neuroimmune inflammation and multiple sclerosis.

The effect of herpes simplex virus-1 on nitric oxide synthase in the rat brain: the role of glucocorticoids.

Objective: Herpes simplex virus-1 (HSV-1) is a common cause of viral encephalitis manifested by activation of the adrenocortical axis, fever and behavioral changes. We investigated the early effects of HSV-1 on constitutive (c) and inducible (i) nitric oxide synthase (NOS) activity in rat brain and in mixed glial cell culture. The effect of glucocorticoids (GCs) on NOS responses to HSV-1 was also determined.

The effect of restraint stress on glucocorticoid receptors in mouse spleen lymphocytes: involvement of the sympathetic nervous system.

Objective: Reciprocal pathways of interaction between the nervous and immune systems during stress may be regulated by stress-induced circulating glucocorticoids that act via type II glucocorticoid receptors (GRs). The aim of the present study was to investigate the effect of restraint stress on GRs in lymphocytes and the role of the sympathetic system in this effect.

Methods: We used male Balb/c mice which were adrenalectomized 3 days before exposure to restraint stress (4 h).

Glucocorticoid resistance following herpes simplex-1 infection: role of hippocampal glucocorticoid receptors.

Herpes simplex-1 (HSV-1) is a sporadic cause of viral encephalitis. We have previously demonstrated that corneal HSV inoculation markedly activates the hypothalamo-pituitary-adrenal (HPA) axis. This activation depends on host derived brain interleukine-1 and was resistant to pretreatment with dexamethasone (dex), possibly because immune factors such as pro-inflammatory cytokines can modify the binding capacity of glucocorticoids in the hippocampus.

The involvement of glucocorticoids and interleukin-1 in the regulation of brain prostaglandin production in response to surgical stress.

Background: This study examined the role of glucocorticoids (GC) and interleukin-1 (IL-1) in regulating the production of brain prostaglandin E(2) (PGE(2)) in response to surgical stress.

Methods: Surgical stress was induced in rats by laparotomy or exploration of the carotid. PGE(2) ex vivo production was measured in the frontal cortex or central amygdala of adrenalectomized rats, or of rats treated with either the GC type II receptor blocker (RU38486) or synthetic GC (dexamethasone).

Regulatory role of the pituitary-adrenal axis in experimental colitis: effect of adrenalectomy on the clinical course and the TH1/TH2 immune profile.

Background: The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in modulating immune reactions in inflammatory bowel disease. Our aim was to assess the role of the HPA axis in the pathogenesis of immunomediated colitis in mice.

Methods: Trinitrobenzene sulfonic acid (TNBS) colitis was induced in Balb/c mice.

Role of the central amygdala in modulating the pituitary-adrenocortical and clinical responses in experimental herpes simplex virus-1 encephalitis.

The amygdala is known to regulate neuroendocrine and behavioral responses to a variety of stimuli. Herpes simplex virus-1 (HSV-1) is the common cause of viral encephalitis, manifested by hypothalamic-pituitary-adrenal (HPA) axis activation, fever, hypermotor activity and aggression. We examined here the role of the central amygdala (cAMG) in regulating the HPA axis function, febrile and behavioral responses to HSV-1 infection in rats.

Adrenocortical axis responses to adrenergic and glutamate stimulation are regulated by the amygdala.

We have examined the effect of lesions of the central and medial amygdala on the pituitary-adrenal responses to noradrenergic stimulation and to the injection of glutamate into the paraventricular nucleus. Bilateral lesions of the amygdalar nuclei inhibited adrenocorticotrophic hormone and corticosterone responses to electrical stimulation of the ventral noradrenergic bundle, and to the injection of the alpha1-adrenergic agonist phenylephrine or glutamate. These results suggest that the amygdala may facilitate the stimulatory roles of noradrenaline and glutamate on the adrenocortical axis.

Effects of surgical stress on brain prostaglandin E2 production and on the pituitary-adrenal axis: attenuation by preemptive analgesia and by central amygdala lesion.

Surgical stress is the combined result of tissue injury, anesthesia, and postoperative pain. It is characterized by elevated levels of adrenocorticotropin (ACTH), corticosterone (CS), and elevated levels of prostaglandin E2 (PGE2) in the periphery and in the spinal cord. The present study examined the effects of perioperative pain management in rats undergoing laparotomy on serum levels of ACTH, CS, and on the production of PGE2 in several brain regions, including the amygdala.

Immunization with a nonpathogenic HSV-1 strain prevents clinical and neuroendocrine changes of experimental HSV-1 encephalitis.

We examined whether immunization with the nonpathogenic strain R-15 of herpes simplex virus-1 (HSV-1) may prevent the clinical and neuroendocrine changes induced by the pathogenic HSV-1 strain Syn17+. Inoculation of strain Syn17+ to control rats induced fever, marked motor hyperactivity and aggressive behavior, and increased serum ACTH, corticosterone (CS) and brain prostaglandin-E2 production. Mortality was 100%.

Involvement of endogeneous glutamate in the stimulatory effect of norepinephrine and serotonin on the hypothalamo-pituitary-adrenocortical axis.

The effects of ionotropic glutamate receptor antagonists on the pituitary adrenal responses following injections of norepinephrine (NE) and serotonin (5-HT) receptor agonists into the hypothalamic paraventricular nucleus (PVN) or electrical stimulation of central NE and 5-HT pathways were studied in anesthetized male rats. PVN injections of an alpha(1)-adrenergic receptor agonist or a serotonergic 5-HT(1A) receptor agonist markedly increased both adrenocorticotropin (ACTH) and corticosterone (CS) serum levels. These responses were significantly inhibited by separate pre-injection of the selective non-NMDA and NMDA glutamate receptor subtype antagonists into the PVN in a dose-dependent manner.

Intracerebral HIV-1 glycoprotein 120 produces sickness behavior and pituitary-adrenal activation in rats: role of prostaglandins.

HIV infection is associated with profound neurobehavioral and neuroendocrine impairments. Previous studies demonstrated that HIV causes neuropathological alterations indirectly, via shedding of glycoprotein 120 (gp120) within the brain. To extend these findings, we examined the neurobehavioral and neuroendocrine effects of central administration of gp120, as well as the role of brain prostaglandins in mediating these effects.

Further evidence for the central effect of dexamethasone at the hypothalamic level in the negative feedback mechanism.

The site of action of glucocorticoids (GC) in exerting negative feedback upon the hypothalamo-pituitary-adrenocortical (HPA) axis is not yet clear. In the present study we have examined whether dexamethasone (Dex) can inhibit the HPA axis stress responses by acting locally at the hypothalamic level in freely moving male rats. Local micro-injection of Dex in the paraventricular nuclei (PVN; 1 microg) prevented a decrease of CRH-41 content in the median eminence.

The amygdala regulates the pituitary-adrenocortical response and release of hypothalamic serotonin following electrical stimulation of the dorsal raphe nucleus in the rat.

The amygdala is known to modulate the function of the hypothalamo-pituitary-adrenocortical (HPA) axis, but the mechanism of this effect is still not clear. In the present study we examined the specific role of the serotonin (5-HT) system in mediating the effect of the amygdala on the activity of the HPA axis. Bilateral lesions of the amygdala in rats reduced the adrenocorticotropin (ACTH) and corticosterone responses to electrical stimulation of the dorsal raphe nucleus, where the cell bodies of serotonergic neurons are located.

Evidence for a mutual interaction between noradrenergic and serotonergic agonists in stimulation of ACTH and corticosterone secretion in the rat.

We investigated the mutual interactions between hypothalamic norepinephrine (NE) and serotonin (5-HT) in mediating the ACTH and corticosterone responses to direct stimulation of the paraventricular nucleus (PVN) with adrenergic and serotonergic agonists. The hormone responses to the intrahypothalamic injection of the alpha1-adrenergic agonist phenylephrine (20 nmol/2 microl) were significantly reduced by prior depletion of hypothalamic 5-HT with intra-PVN injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), but not after depletion of hypothalamic NE by intra-PVN injection of the noradrenergic neurotoxin 6-hydroxydopamine (6-OHDA). The ACTH and corticosterone responses to intrahypothalamic injection of the 5-HT(1A) receptor agonist 8-OH-DPAT (20 n mol/2 microl) were significantly reduced by depletion of hypothalamic NE with 6-OHDA, but not after depletion of hypothalamic 5-HT with 5,7-DHT.

Involvement of brain cytokines in the neurobehavioral disturbances induced by HIV-1 glycoprotein120.

Intracerebroventricular (i.c.v.

Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids.

The aim of this study was to investigate the specific role of endogenous glucocorticoids (GC) following restraint stress on thymic involution and apoptosis. Restraint stress has been reported to alter physiological and behavioral responses in experimental animals. Exposure of mice to restraint stress led to involution of the thymus, to a decrease of the CD4+ 8+ thymocyte subset, and to fragmentation of thymic DNA.