Acute ethanol intake attenuates inflammatory cytokines after brain injury in rats: a possible role for corticosterone.

It has been reported that acute ethanol intoxication exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI), although the mechanism(s) has not been determined. Given that pro-inflammatory cytokines are either neuroprotective or neurotoxic, depending on their tissue levels, ethanol-induced alterations in brain cytokine production may be involved in determining the recovery after TBI. The present study was undertaken to examine the effect of acute ethanol pretreatments (producing blood alcohol concentrations of 100+/-16 mg/dL, and 220+/-10 mg/dL, considered low and intoxicating doses, respectively) on interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels in discrete brain regions.

Ileal nitric oxide formation is altered in the young rat in response to endotoxin: effects of exposure to alcohol in utero.

This study was designed to test the hypothesis that the activity and expression of iNOS in the ileum will be altered in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day-old rats, were progeny of dams fed an alcohol diet during gestation and their pair-fed/control cohorts. We determined the effects of endotoxin administration on ileal iNOS enzymatic activity and on ileal iNOS immunoreactivity.

Sympathetic neural response to immune signals involves nitric oxide: effects of exposure to alcohol in utero.

In response to infection, inflammation, or injury, the neural-immune-endocrine networks are activated to restore or maintain stability in the internal environment. Disruption of any one of the functional components may impair the effectiveness of the immune response to challenges, and may consequently jeopardize the wellness of the host. Studies in the author's laboratory have shown that the normal activation of splenic sympathetic neurons in response to the endotoxin lipopolysaccharide, a tool frequently used to mimic infection or inflammation, does not occur in fetal alcohol-exposed (FAE) rats.

Splenic sympathetic response to endotoxin is blunted in the fetal alcohol-exposed rat: role of nitric oxide.

This study was designed to test the hypothesis that nitric oxide (NO) mediates the blunted splenic sympathetic response to lipopolysaccharide (endotoxin) that occurs in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day-old rats, were progeny of pregnant dams fed an alcohol diet (35% of the calories were derived from ethanol) or their control and pair-fed (PFC) cohorts. We examined the effects of lipopolysaccharide (LPS) (0.

Exposure to alcohol in utero blunts splenic sympathetic neural response to endotoxin and interleukin-1beta in the rat.

Systemic administration of endotoxin (LPS) or interleukin-1beta (IL-1) to prepubertal rats induced a marked increase in splenic but not cardiac norepinephrine (NE) turnover, an index of sympathetic neural activity. In contrast, the splenic neural response was blunted in their fetal alcohol-exposed (FAE) cohorts. Because the sympathetic outflow to lymphoid organs is considered an important immune modulator, the anomalous neural response to immune signals may partly account for the impaired cellular immunity and, thus, for the increased susceptibility to infections associated with FAE.

Effects of nerve growth factor on splenic norepinephrine and pineal N-acetyl-transferase in neonate rats exposed to alcohol in utero: neuroimmune correlates.

Prenatal alcohol exposure (FAE) has been associated with multiple anomalies, including a selective developmental delay of sympathetic innervation in lymphoid organs. Sympathetic neurons require nerve growth factor (NGF) for their development and maintenance, and recent evidence has suggested that alcohol impairs the synthesis and/or biological activity of NGF in selected central and peripheral neurons. Thus, the present study examined the hypothesis that NGF administration to FAE rats during early postnatal development would reverse some of the peripheral sympathetic deficits.

Ferritin effect on the transverse relaxation of water: NMR microscopy at 9.4 T.

Accumulation of ferritin, the iron storage protein, has been linked recently to aging and a number of pathologies. Noninvasive detection of iron storage by MRI relies on its extremely strong effect on water relaxation. The aim of this article is to characterize the effect of ferritin on transverse water relaxation in a high magnetic field, using an imaging Carr-Purcell Meiboom-Gill (CPMG) preparation sequence.

Prenatal alcohol exposure selectively suppresses cell-mediated but not humoral immune responsiveness.

The present study examined effects of fetal alcohol exposure (FAE) on the ability of peripubertal male and female rats to mount a humoral immune response against T-cell-dependent as well as independent antigens. The appropriate pair-fed (PF) and control (C) cohort rats were included. Serum immunoglobulins (Ig) levels were determined following a primary or secondary immune response.

Systemic interleukin-1 induces early and late patterns of c-fos mRNA expression in brain.

This study was designed to examine the mechanisms by which systemic interleukin-1 affects neuroendocrine systems in the brain. Intraperitoneal injections of interleukin-1 beta (1.25 micrograms/rat) were administered to rats.

Fetal alcohol exposure and adult tumorigenesis.

Adult rats exposed to prenatal alcohol were evaluated for their susceptibility to either hormone- or chemical-inducing tumors. In the first study, rats exposed to prenatal alcohol displayed an increased propensity to beta-estradiol (E2)-induced adenohypophyseal prolactinoma. The susceptibility was manifest as a potentiated increase in anterior pituitary weight as well as in serum prolactin levels after 1 and 3 weeks but not 5 weeks of hormone treatment.

Maternal and paternal alcohol use: effects on the immune system of the offspring.

There is no single mechanism which can account for such a complex biological phenomenon as immune regulation, nor is it clear how alcohol teratogenicity exerts its multiple adversive effects, including lasting immune deficits. Much of the research aimed at unravelling effects of pre- or early postnatal alcohol exposure on the organism's defense mechanisms and long-term health risks has been phenomenological. A better understanding of mechanisms which underlie alcohol effects on immune competency will require integrated studies of the neuro-immune-endocrine networks.

Prenatal alcohol exposure alters the development of sympathetic synaptic components and of nerve growth factor receptor expression selectivity in lymphoid organs.

Exposure to alcohol in utero has been associated with long-term immune deficits. In addition, adult mice exposed to alcohol prenatally display altered noradrenergic synaptic transmission selectively in lymphoid organs. This is consistent with the hypothesis that sympathetic neurons play an important role in immunomodulation.

Developmental delays associated with prenatal alcohol exposure are reversed by thyroid hormone treatment.

Exposure to alcohol in utero has been associated with hypothyroidism and a variety of developmental defects characteristic of thyroid dysfunction. The present work examined whether these abnormalities could be reversed in infant rats treated with thyroid hormones. Subjects were offspring of dams which were on the following diet regimen during gestation: (1) free access to liquid diet containing ethanol (alcohol pups); (2) an equal volume of isocaloric liquid diet (pair-fed pups); or (3) ad libitum control diet (control pups).

Lactational alcohol exposure elicits long-term immune deficits and increased noradrenergic synaptic transmission in lymphoid organs.

Increasing evidence suggests that the sympathetic nervous system plays an important role in immunomodulation. While chronic alcohol consumption has been associated with immune deficits, the effects of exposure to alcohol during early postnatal life on subsequent immunocompetence and activity of sympathetic neurons in lymphoid organs are not known. This study examined the long-term effects of lactational alcohol consumption on cellular immune responses and noradrenergic synaptic transmission in lymphoid and other organs of the young adult C57BL/6 mouse.

Prenatal ethanol exposure alters immune capacity and noradrenergic synaptic transmission in lymphoid organs of the adult mouse.

Clinical and experimental evidence indicates that exposure to alcohol in utero is associated with altered immune capacity. The mechanisms underlying such abnormalities are not clear. However, the suggestion that reciprocal interactions between the immune and the nervous systems are necessary for a competent immune response may be relevant.

Prenatal ethanol exposure impairs lesion-induced plasticity in a dopaminergic synapse after maturity.

This study examined the consequences of alcohol (ethanol) exposure during fetal life on lesion-induced dopaminergic synapse responsiveness (plasticity) in the olfactory tubercle of the adult rat. Normally, in the olfactory tubercle, olfactory bulbectomy elicits alterations in pre- and postsynaptic dopaminergic markers, including, respectively, (1) increased tyrosine hydroxylase activity and immunoreactivity, which is associated with dopaminergic axon sprouting, and (2) increased dopaminergic receptor density and potentiated dopamine activation of adenylate cyclase. We have utilized biochemical and quantitative immunocytochemical methodology to examine these synaptic markers in olfactory bulbectomized or sham-operated adult rats.

Chronic exposure to random restraint stress retards the development of estrogen-induced pituitary prolactinoma in rats.

The effects of stress on carcinogenesis have been equivocal. The present work examined the influence of an unpredictable pattern of chronic restraint stress on estradiol-induced pituitary hyperplasia in male Fischer 344 rats. The animals were grouped as follows: (1) control, (2) stressed, (3) estradiol (31 mg), subcutaneous implant for 40 days and (4) estradiol with stress, 1 h daily, randomly, for 40 days.

Deafferentation elicits a transient decrease in Na+, K+-ATPase activity and ouabain binding in the olfactory tubercle.

This work examines the effects of olfactory bulbectomy on Na+, K+-ATPase activity and ouabain binding in the olfactory tubercle. The activity and number of enzyme sites were reduced significantly in olfactory tubercle, but not in corpus striatum or hippocampus, 14 and 21 days after bulbectomy. Enzyme activity and ouabain binding returned to normal by 42 days after the lesions.

Perinatal, not adult, hypothyroidism suppresses dopaminergic axon sprouting in the deafferented olfactory tubercle of adult rat.

We reported recently that chronic thyroid deficiency in rat, beginning in utero and terminating after maturity, suppresses lesion-induced central catecholaminergic axon sprouting in the adult brain [Gottesfeld et al, 1985]. The present work was undertaken to define the critical period of hypothyroidism on subsequent neuronal sprouting. Thyroid hormones deficiency was induced in rats by methimazole during (a) gestational days 8-21 (20 mg/kg/day in the drinking water); (b) postnatal days 1-15 (0.

Restraint stress during late pregnancy in rats elicits early hypermyelination in the offspring.

Female rats were subjected to a regular, daily schedule of 2 hr of restraint stress during the final 6 days of pregnancy. During the first 2 postnatal weeks, adrenal weights were greater than normal in the offspring of the stressed dams. The concentration of brain myelin was higher than control at 14 and 21 days of age but similar to normal by day 40.

Deafferentation elicits increased dopamine-sensitive adenylate cyclase and receptor binding in the olfactory tubercle.

Removal of a major non-catecholaminergic output from the olfactory bulb elicits sprouting of dopaminergic axons in the olfactory tubercle. The functional consequences of this increased dopaminergic innervation are presently not known. This study examined the question of whether lesion-induced sprouting of dopaminergic axons is associated with changes in dopamine-sensitive adenylate cyclase and dopamine receptor density in the partially denervated olfactory tubercle.

Prenatal and postnatal hypothyroidism abolishes lesion-induced noradrenergic sprouting in the adult rat.

The effects of altered thyroid states on regeneration in the central nervous system are equivocal. This work was undertaken to examine the influence of propylthiouracil-induced (PTU-induced) pre- and postnatal hypothyroidism on collateral sprouting of noradrenergic (NA) axons in the habenula (Hb), following lesions in the stria medullaris (SM) of the adult rat. Ten pregnant dams were divided into control and PTU-treated groups.

High-affinity uptake of neurotransmitters in rat neostriatum: effects of aging.

High-affinity uptake of dopamine (DA), glutamate, and gamma-aminobutyric acid (GABA) was determined in crude synaptosomal preparations from neostriatal regions of rats 7, 17, and 27 months of age. Dopamine uptake was highest in rostral neostriatum, but no age-related differences were detected. On the other hand, the high-affinity uptake of both GABA and glutamate was increased with age.

Regional analysis of neostriatal cholinergic and dopaminergic receptor binding and tyrosine hydroxylase activity as a function of aging.

Tyrosine hydroxylase (TH) activity, as well as dopaminergic and cholinergic muscarinic receptor binding were measured in discrete regions of the neostriatum of rats 7, 17, and 27 months old. Activity of TH was highest in the rostral neostriatum as compared to the caudal region. Age-related differences in TH were detected in only one region.