Biomedical subjects

J R West

Publications and source records attributed to J R West.

At least 55 records · Page 3Linked to original sources

PubMed1997

Fetal alcohol exposure and temporal vulnerability regional differences in alcohol-induced microencephaly as a function of the timing of binge-like alcohol exposure during rat brain development.

In humans, microcephaly (small head for body size) is a common feature of fetal alcohol syndrome. An analogous measure, termed microencephaly (small brain for body size), can be used for evaluating the detrimental effects of the differential timing of alcohol exposure on brain development in animal model systems. Timed-pregnant rats were exposed to binge-like alcohol during either the first 10 days (first trimester equivalent) or second 10 days of gestation (second trimester equivalent), or the combination of first and second trimesters equivalent for prenatal treatments. Offspring from some of the animals exposed to alcohol during the combined first and second trimesters equivalent were raised artificially from postnatal day (P) 4 through P9 (part of the third trimester equivalent), and also received binge-like alcohol during this period, producing animals that were exposed to alcohol during all three trimesters equivalent. Offspring from untreated dams were also raised artificially and received alcohol only from P4 to P9, thus creating animals that were exposed to alcohol only during part of the third trimester equivalent. All pups were perfused on P10. Appropriate controls (nutritional and normally reared) were used for every alcohol treatment combination. Peak blood alcohol concentrations were not different among the treatment groups for a given sampling time. Significant somatic growth deficits occurred in offspring exposed to alcohol for the equivalent of all three trimesters, compared with offspring exposed to alcohol during other periods. Brain growth in offspring also was significantly affected by the timing of alcohol exposure. The whole brain, forebrain, and cerebellum to body weight ratios of pups exposed to alcohol during the third trimester had more significant brain growth deficits than pups in groups exposed to alcohol during other times of brain development. Although alcohol exposure during the third trimester had a significant detrimental impact on overall brain growth, significant differences in temporal vulnerability were also found for the brainstem to body weight ratios. Offspring of dams exposed to alcohol during the first trimester had the same magnitude of deficit as those exposed to alcohol during the third trimester, and those two groups were significantly deficient compared with the groups exposed to alcohol at other times, suggesting some differential vulnerability of this region to alcohol-induced injury at different times of development. This study is the first thorough examination of microencephaly and gross regional vulnerability of the developing brain as related to temporal factors of alcohol exposure in an animal model system, and the results support and expand on the findings of the available clinical literature. Furthermore, our results substantiate claims that the cessation of alcohol before the third trimester can lessen the severity of some alcohol-related birth deficits.

Alcoholic Intoxication↗

PubMed1997

Ethanol reduces expression of the nerve growth factor receptor, but not nerve growth factor protein levels in the neonatal rat cerebellum.

The cerebellum is especially vulnerable to ethanol's neurotoxic effects during development, and ethanol exposure during the brain growth spurt will deplete cerebellar neurons. The mechanisms undertying this neuronal cell loss remain elusive. Nerve growth factor (NGF) is a neurotrophin that promotes cell survival in various brain areas, and there is evidence that NGF may play a role in the developing cerebellum. This study examined whether ethanol exposure of the neonatal rat cerebellum altered the levels of either NGF or the expression of p75 and trkA, which are two components of the NGF receptor. Ethanol exposure had no effect on NGF levels in the neonatal cerebellum, as determined by an NGF-specific ELISA. Immunohistochemical labeling techniques indicated that both the p75 and trkA NGF receptors were expressed on Purkinje cell dendrites in the developing cerebellum, with posterior lobules expressing higher levels of p75 and trkA NGF receptor, compared with anterior lobules. Ethanol exposure of neonatal rats reduced the expression of both p75 and trkA NGF receptors on the Purkinje cell dendrites. These results suggest that ethanol could interfere with neurotrophic support of Purkinje cells by reducing the levels of available NGF receptor.

Animals↗

PubMed1997

Nerve growth factor and basic fibroblast growth factor protect rat cerebellar granule cells in culture against ethanol-induced cell death.

Neuronal cell loss is one of the most debilitating effects of fetal ethanol exposure. Cultures of cerebellar granule cells are a useful model to investigate ethanol neurotoxicity, because ethanol depletes cell numbers in these cultures, which also occurs in vivo. The primary goal of the present study was to identify and characterize agents that can ameliorate the ethanol-induced cell death that occurs in this culture system. Growth factors, such as nerve growth factor (NGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and insulin-like growth factor-I (IGF-I) can prevent neuronal degeneration after toxic insult in various experimental paradigms. These growth factors were investigated in the current study to determine whether or not they can mitigate ethanol-induced death of cerebellar granule cells in culture. Results indicate that NGF and bFGF significantly reduced the ethanol-induced cell loss. Both the NGF- and bFGF-mediated neuroprotection required protein and RNA synthesis, because actinomycin D (RNA synthesis inhibitor) and cycloheximide (protein synthesis inhibitor) blocked their neuroprotective effects. In addition to its neuroprotective effect, bFGF also had a neurotrophic effect and could enhance cell survival in the absence of ethanol exposure. NGF did not have a neurotrophic effect. Neither EGF nor IGF-I was neuroprotective, although the latter did have a substantial neurotrophic effect. In conclusion, bFGF and NGF have long been recognized for their role in enhancing neuronal cell survival and differentiation. This study suggests that these growth factors can also provide neuroprotection against ethanol-induced cell death.

Animals↗

PubMed1996

Ethanol exposure reduces the density of the low-affinity nerve growth factor receptor (p75) on pheochromocytoma (PC12) cells.

Although ethanol is detrimental to the developing nervous system, the mechanism(s) by which ethanol produces neuronal damage is (are) not clear. One potential mechanism is ethanol-induced inhibition of neurotrophic support. This study utilized an in vitro model, pheochromocytoma PC12 cells, to examine the effect of ethanol on the nerve growth factor (NGF) receptor. NGF binding studies indicated that ethanol exposure (400 mg/dl for 4 days) reduced the density of the low-affinity (p75) NGF receptor on PC12 cells, but had no effect on the density of the high-affinity NGF receptor. The equilibrium dissociation constants (Kd) for both the low-affinity and high-affinity NGF receptors were unaffected by ethanol. Low-affinity NGF binding is mediated by the p75 component of the NGF receptor. Quantification of p75 by immunoprecipitation revealed that ethanol reduced the level of p75 in PC12 cells. However, Northern analysis indicated that the p75 mRNA was not reduced by ethanol exposure, raising the possibilities that ethanol inhibited translation of p75 or incorporation of the p75 protein into the plasma membrane. This work is consistent with the hypothesis that ethanol's detrimental effects may be produced in part by inhibition of neurotrophic support at the receptor level.

Animals↗

PubMed1996

Cocaine exposure during the brain growth spurt failed to produce cerebellar Purkinje cell loss in rat pups.

Previous studies in our laboratory indicated that cocaine exposure during the brain growth spurt period, a developmental stage vulnerable to various teratogens, did not produce microencephaly (gross brain weight measures). However, neonatal cocaine exposure has been shown to affect motor coordination and balance, which are both sensitive to cerebellar damage. The purpose of this study was to investigate whether cocaine exposure during the brain growth spurt period could result in the loss of cerebellar Purkinje cells, a neuronal population known to be vulnerable to other teratogenic insults. Sprague-Dawley rat pups were randomly assigned to either cocaine-treated groups (40, 80 mg/kg s.c.) or a gastrostomy control group, and were reared using an artificial-rearing method from postnatal days (PDs) 4 through 9. On PD 10, these animals were perfused and the cerebella were extracted and processed for cell counts. Estimates of Purkinje cell numbers were obtained using a 3-dimensional optical dissector method. The results using this stereological method demonstrated no significant Purkinje cell loss in response to cocaine treatment, even at a dose which has been shown to result in high mortality. The failure of cocaine to produce significant Purkinje cell loss (present finding) or microencephaly (previous finding) odds to the evidence indicating that cocaine is not a potent neuroteratogen.

Analysis of Variance↗

PubMed1996

Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation.

The most serious features of fetal alcohol syndrome (FAS) are mental retardation and other behavioral problems resulting from alcohol-induced damage to the developing central nervous system (CNS). The mechanism by which alcohol induces its neuroteratogenic effects is unknown. One hypothesis is that gestational alcohol exposure results in a reduction in neuronal number. This study demonstrates that gestational exposure to ethanol in a non-human primate species induces permanent dose-related deficits in the number of cerebellar Purkinje cells. Ethanol was administered via nasogastric tube once per week to 15 gravid pigtailed macaques (Macaca nemistrina) in one of the following doses: 0.0 (intubated controls), 1.2, 1.8, 2.5, 3.3, and 4.1 g/kg/dose. Offspring were reared with parental surrogates and were sacrificed at 6 months of age; 8-microns-thick, parasagittal sections were cut through the paraffin-embedded cerebellar vermis. Purkinje cells were quantified, the length of the Purkinje cell line was determined stereologically, and Purkinje cell linear frequency was calculated. The number of Purkinje cells and their linear frequencies were significantly reduced in the alcohol-treated subjects, and the deficits were dose-dependent. The groups receiving 2.5 g/kg/dose and above were most severely affected and had an average deficit in Purkinje cell number of 11.8%, relative to controls. Alcohol had no effect on the length of the Purkinje cell line. The findings suggest that alcohol-induced reduction in neuronal number may be an important factor underlying the CNS dysfunction in FAS.

Animals↗

PubMed1996

Behavioral deficits induced by bingelike exposure to alcohol in neonatal rats: importance of developmental timing and number of episodes.

The importance of the timing and number of episodes of bingelike alcohol exposure in neonatal rats on subsequent behavioral outcomes was evaluated with a parallel bar task and a spatial conditional alternation task. Different groups of Sprague-Dawley rat pups were exposed to alcohol delivered via artificial rearing procedures either on postnatal Days (PD) 4 and 5, on PD 8 and 9, or on both PD 4/5 and 8/9 (Combined), producing daily peak blood alcohol concentrations around 400 mg/dl. Controls included an artificially reared group and a normally reared group. Exposure during PD 4/5 produced significantly more severe motor deficits and significantly more severe reductions in cerebellar and brainstem weights than did exposure on PD 8/9. Combined exposure produced greater deficits on these measures than either of the limited exposures. Significant deficits in the acquisition rates for conditional alternation were found only with the Combined exposure, although both the PD 8/9 and Combined groups committed significantly more within-trial errors. All three alcohol treatments produced significant and comparable reductions in forebrain weight. The type and severity of behavioral and neural deficits induced by neonatal bingelike alcohol exposure depend on the timing and number of exposures.

Alcoholic Intoxication↗

PubMed1996

Prenatal binge-like alcohol exposure alters neurochemical profiles in fetal rat brain.

The majority of studies examining the effects of prenatal exposure to alcohol on neurotransmitter levels have furnished results that are divergent (increase, decrease or no change). The present study assessed six neurochemical compounds [norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), gamma-aminobutyric acid (GABA)] from the same brain tissue. Pregnant Sprague-Dawley rats were given 5.1 g/kg alcohol (by gavage) either daily from embryonic day 1 (E1) through E20 or E20 only. In addition, pairfed/intubated (PF/INT) and ad lib chow (Chow) groups were included as controls. The dams were sacrificed and the fetuses were removed on E20. Binge-like alcohol exposure throughout gestation (E1-E20) produced significantly higher brain to body weight ratios compared with all other groups. Alcohol exposure did not produce changes in NE levels, although the E1-E20 exposure to alcohol reduced the contents of DA and 5-HT compared with the PF/INT and Chow controls. In addition, the E20 alcohol treatment reduced both DA and 5-HT levels compared with the E1-E20 alcohol treatment. DOPAC and 5-HIAA contents were affected by the prenatal treatments insofar as the 5-HIAA levels were decreased in E/1-20 and E20 animals relative to both controls, while the DOPAC levels were decreased in E/1-20, E20 and PF/INT groups compared to the Chow group; however, both metabolites were unaffected by the difference in alcohol treatment duration. Moreover, GABA levels were increased in fetuses exposed to alcohol from E1-E20 compared with all other groups. Collectively, these findings suggest that binge-like alcohol exposure prior to and during neurotransmitter development affects the baseline content of several neurotransmitters.

Amniotic Fluid↗

PubMed1996

Long-term effect of postnatal alcohol exposure on the number of cells in the neocortex of the rat: a stereological study.

Behavioral and morphological studies suggest that exposure to alcohol during development may cause damage in the neocortex. In this study, rat pups were exposed to alcohol during the brain growth spurt and examined at adulthood to ascertain the long-term effect of alcohol exposure on the neocortex. Four-day-old rat pups were surgically implanted with an intragastric cannula while under ether anesthesia and artificially reared from postnatal day (PN) 4 through PN11. Two of the consecutive 12 daily feeds contained either alcohol (4.5 g/kg; alcohol-exposed) or an isocaloric maltose/dextrin solution (gastrostomy control) from PN4 through PN9. On PN115, animals were perfused intracardially and the brains removed. Unbiased stereological methods were used to determine the neocortical volume, the total number of neurons and glial cells in the entire neocortex and in layer V, and the mean cell volume of neurons or mean nuclear volume of glial cells in layer V. No effect of alcohol was seen in the neuronal population on either cell number or mean cell volume, nor was there any difference in the total number or mean nuclear volume of glial cells in layer V. These findings suggest that neither the entire neocortex nor layer V alone are vulnerable to permanent alcohol-induced cell death.

Animals↗

PubMed1996

Acute hemodynamic, pituitary, and adrenocortical responses to alcohol in adult female sheep.

Alcohol was infused intravenously into chronically cannulated adult female sheep as a 40% solution (w/v) at doses of 0.5, 1.0, 1.5, or 2.0 g/kg over 1 hr. Saline infusions, equal in volume to the highest dose, served as a control. Dose-dependent peak blood alcohol concentrations (BACs) were attained 60 min after the beginning of alcohol infusion for all doses (86.5 +/- 3.7, 213.2 +/- 11.0, 373.2 +/- 14.3, and 494.1 +/- 34.5 mg/dl +/- SE, respectively). Plasma cortisol concentrations increased in response to the 0.5 g/kg infusions (BACs less than 100 mg/dl), whereas both ACTH and cortisol concentrations increased in the 1.0 and 2.0 g/kg dose groups. Mean arterial pressure, heart rate, and Paco2 increased, whereas Pao2 decreased in response to the 1.5 and 2.0 g/kg infusions. Arterial pH declined in the highest dose group. Respiratory rate was lower in all groups receiving alcohol compared with that of the control group. Hematocrit did not change. We conclude that BACs in adult female sheep below 100 mg/dl (levels easily achieved by social drinkers) result in activation of the hypothalamus-pituitary-adrenal axis. At high BACs (> 350 mg/dl), pituitary adrenal responses are accompanied by increases in heart rate, blood pressure, and Paco2 and decreases in Pao2 and arterial pH. These findings support the hypothesis that alcohol acts directly on the brain to mediate pituitary adrenal responses and that the additional responses to high BACs (the blood gas and hemodynamic responses), might be mediated by direct actions of alcohol on the brain, by cerebral ischemia, or by alcohol-mediated suppression of ventilatory drive and hypoxemia.

Adrenocorticotropic Hormone↗

PubMed1995

Permanent neuronal cell loss in the cerebellum of rats exposed to continuous low blood alcohol levels during the brain growth spurt: a stereological investigation.

This study demonstrates that exposure to an alcohol regimen that resulted in low, uniform blood alcohol concentrations during a period of rapid brain growth can lead to a permanent deficit in the number of Purkinje cells and granule cells in the floccular-parafloccular region of the cerebellum. Sprague-Dawley rat pups were artificially reared and were administered alcohol over postnatal days 4 through 9, a period of brain development similar to that of the human third trimester. Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 10.2% solution in two of the 12 daily feedings (10.2% group) or as a 5.1% solution in four of the 12 feedings (5.1% group). A third group received a daily dose of 6.6 g/kg administered as a 2.5% solution in every feeding (2.5% group). The condensed patterns of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance while the higher daily dose (6.6 g/kg), administered continuously, resulted in low but continuous blood alcohol concentrations. Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of Purkinje cells and granule cells in the floccular-parafloccular region of the cerebellum was estimated using unbiased stereological methods. Exposure to alcohol resulted in significant deficits in the number of both Purkinje cells and granule cells at 115 days of age in all three treatment groups. Most importantly a significant deficit of Purkinje cells and granule cells was found following continuous exposure to low blood alcohol concentrations, i.e., in the 2.5% group. The total number of Purkinje cells in the 2.5% group was 2.33 +/- 0.31 x 10(4) compared with 3.18 +/- 0.30 x 10(4) in the artificially reared controls. The total number of granule cells in the 2.5% group and the controls was 1.24 +/- 0.10 x 10(7) and 1.64 +/- 0.19 x 10(7), respectively. These results support the hypothesis that exposure to a continuous, low blood alcohol concentration can result in the death of developing neurons and lead to permanent neuronal deficits. The degree of neuronal loss does not correlate with the magnitude of the peaks of blood alcohol concentration.

Analysis of Variance↗

PubMed1995

NMDA prevents alcohol-induced neuronal cell death of cerebellar granule cells in culture.

Neuronal cell loss is one of the most debilitating effects of alcohol exposure during development of the nervous system. In this study, primary cultures of neuronal cells (cerebellar granule cells) were used to examine mechanisms of alcohol-induced neuronal cell death. Previously, we established that (Pantazis et al., Alcohol Clin Exp Res 17:1014-1021, 1993): (1) alcohol exposure caused neuronal cell death in cultures of cerebellar granule cells and this cell loss was both time-dependent and dose-dependent; and (2) the vulnerability of cerebellar granule cells to alcohol-induced loss changed with the length of time the cells were in culture before initiating alcohol exposure-that is, younger cultures (1 day in vitro) were much more susceptible to alcohol-induced neuronal cell death than older cultures (4 or 7 days in vitro). The primary goal of the present study was to examine the potential role of the NMDA receptor in alcohol-induced death of cerebellar granule cells in culture. Experiments were performed to test the hypothesis that the alcohol-induced death of cerebellar granule cells can be prevented or reduced by NMDA treatment. Our results indicate that stimulation of the NMDA receptor has a neuroprotective effect and can significantly reduce the alcohol-induced neuronal cell death of newly established cerebellar granule cell cultures. This neuroprotective effect of NMDA is blocked by 2-amino-5-phosphonovalerate, a competitive inhibitor of the NMDA receptor, confirming that this neuroprotective effect is mediated via the NMDA receptor. This is the first report that alcohol's neurotoxic effect can be ameliorated by activation of the NMDA receptor.

Animals↗

PubMed1995

Changes in blood alcohol levels as a function of alcohol concentration and repeated alcohol exposure in adult female rats: potential risk factors for alcohol-induced fetal brain injury.

Fetal alcohol syndrome and alcohol-related birth defects are the result of heavy maternal alcohol consumption during gestation. The magnitude of deficit manifested by the offspring is invariably a consequence of several risk factors that may result in high peak blood alcohol concentrations (BACs), such as the duration, timing, or pattern of alcohol consumption. In addition, the alcohol content of the consumed beverage may play a role in determining offspring developmental consequences. Because higher BACs are positively correlated with risk and severity of brain injury early in postnatal life, initially it was important to determine how BAC is influenced by alcohol concentration and whether that influence is constant over repeated alcohol treatments. Groups of female Sprague-Dawley rats received daily intragastric intubations of 5 g/kg alcohol in one of several concentrations: 45% (v/v), 30% (v/v), 22.5% (v/v), or 15% (v/v) for a duration of 18 consecutive days. Blood samples were taken at various times postintubation on days 3, 8, 13, and 18 of treatment, and analyzed by headspace gas chromatography. Multivariate analyses of peak BAC, average BAC, and time to reach peak BAC revealed some noteworthy results. First, peak BAC and average BAC were significantly lower in the 45% group, compared with the other concentration groups, whereas this group also took a longer time to reach peak BAC than the other three groups. Second, peak BAC and average BAC were higher on the last day of treatment than any of the other treatment days. These results suggest that alcohol concentration and repeated alcohol exposure can influence BAC and, as such, are important risk factors to be considered in the appraisal of alcohol-induced fetal brain injuries.

Animals↗

PubMed1995

Permanent neuronal cell loss in the inferior olive of adult rats exposed to alcohol during the brain growth spurt: a stereological investigation.

The purpose of this study was to examine whether exposure of rat pups to alcohol postnatally over a period of brain development similar to that of the human 3rd trimester results in a permanent loss of cells in the inferior olivary nucleus. It was hypothesized that a deficit of neurons in the inferior olive, the sole source of climbing fibers, may contribute to the cerebellar dysfunction observed following exposure to alcohol during development. Sprague-Dawley rat pups were artificially reared and administered alcohol over postnatal days 4-9. One artificially reared group received a daily alcohol dose of 4.5 g/kg, administered as a 10.2% solution in 2 of 12 daily feedings (10.2% group). This pattern of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance. The other artificially reared group was fed a diet made isocaloric to the alcohol-containing diet (gastrostomy control group). Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of neurons in the inferior olivary nucleus was estimated using unbiased stereological methods. Exposure to alcohol resulted in a significant deficit in the number of neurons in the inferior olive at 115 days of age. The total number of neurons in the alcohol-exposed group was 40.12 +/- 8.7 x 10(3), compared with 53.37 +/- 3.7 x 10(3) in the artificially reared controls. These results indicate that there is a permanent deficit of neurons in the inferior olive after postnatal exposure to alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Alcohol-induced brain growth restrictions (microencephaly) were not affected by concurrent exposure to cocaine during the brain growth spurt.

The prevalence of concomitant use of alcohol and cocaine among drug abusers has raised concern about the possible increased risk of fetal damage. The aim of this study was to assess the interactive effects of alcohol and cocaine on lethality, somatic growth, and brain growth using an animal model system. Sprague-Dawley rat pups were used as subjects. They were randomly assigned to 1 of the 9 artificially reared groups which varied with respect to the combination treatments of cocaine (0, 40, or 60 mg/kg) and alcohol (0, 3.3, or 4.5 g/kg). All artificially reared pups were given daily cocaine and alcohol treatments during a major part of the brain growth spurt period (postnatal days 4-9). An additional group of suckled control animals raised by their natural dams was included to control for artificial rearing. The results are summarized as follows: 1) Drug-induced lethality was higher in cocaine-treated groups when compared with non-cocaine-treated groups, and the concurrent administration of high doses of alcohol and cocaine significantly increased the mortality rate. 2) Somatic growth, in terms of body weight, was not affected by alcohol, cocaine, or the combination of both drugs using the artificial rearing technique. 3) Alcohol exposure during this brain growth spurt period significantly reduced whole brain weight, as well as forebrain, cerebellum, and brain stem weights. 4) In contrast to alcohol, cocaine failed to exert a detrimental effect on brain weight measures during this early postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Fetal alcohol syndrome: the vulnerability of the developing brain and possible mechanisms of damage.

Fetal alcohol exposure has multiple deleterious effects on brain development, and represents a leading known cause of mental retardation. This review of the effects of alcohol exposure on the developing brain evaluates results from human, animal and in vitro studies, but focuses on key research issues, including possible mechanisms of damage. Factors that affect the risk and severity of fetal alcohol damage also are considered.

Animals↗

PubMed1994

Recent findings on the mechanisms by which alcohol damages the developing nervous system.

General etiologic categories related to possible mechanisms of fetal alcohol-induced brain damage are explored. Possible general mechanisms include alterations in protein synthesis, prostaglandins, gangliosides, hypoxia and free radical damage. A multiple systems cascade is presented to illustrate how multiple mechanisms could act together to produce a variety of effects.

Animals↗

PubMed1993

Transient cortical astrogliosis induced by alcohol exposure during the neonatal brain growth spurt in rats.

The astrocyte response to central nervous system injury induced by neonatal alcohol exposure was evaluated using radioimmunoassay and immunocytochemistry of glial fibrillary acidic protein (GFAP). Rat pups were exposed to alcohol on postnatal days 4 through 9 via artificial rearing. Alcohol solutions were administered as one of the following treatments: 10.2% (v/v) in two feedings (4.5 g/kg/day), 5.1% (v/v) in four feedings (4.5 g/kg/day), or 2.5% (v/v) in 12 feedings (6.6 g/kg/day), producing mean blood alcohol concentrations (BACs) of approximately 300, 180, and 50 mg/dl, respectively. Littermates were included as gastrostomy controls (GC) and suckle controls (SC). On postnatal day 10, GFAP concentration increased as a function of BAC, and the 10.2% alcohol treatment significantly and dramatically increased GFAP in the cortex (325% of SC). GFAP immunocytochemistry revealed frequent loci of heavily labeled reactive astrocytes surrounding small cortical blood vessels in the 10.2% group. In addition, a generalized increase in GFAP immunoreactivity was present in the deep layers of the cortex in all alcohol groups, marked by astrocytic fibrillary hypertrophy and increased density. Three-dimensional counts in layer V of parietal cortex using confocal microscopy indicated that the density of GFAP-labeled astrocytes of the 10.2% group was twice that of controls. The layer V gliosis was observable even at low BACs, while gliosis around the vasculature occurred only with high BACs. By postnatal day 15, the astroglial effects were no longer evident. These transient astroglial reactions likely constitute an important aspect of cortical pathophysiology resulting from binge alcohol exposure during the brain growth spurt of the third trimester equivalent.

Analysis of Variance↗