Biomedical subjects

M Hallak

Publications and source records attributed to M Hallak.

90 records · Page 5Linked to original sources

PubMed1989

Physostigmine, tacrine and metrifonate: the effect of multiple doses on acetylcholine metabolism in rat brain.

The effects of two consecutive intramuscular doses of three cholinesterase inhibitors (physostigmine, tetrahydroaminoacridine and metrifonate) were compared in rats. The results revealed major differences in biochemical effects on the brain of the rat including the extent and duration of inhibition of cholinesterase, inhibition of release of acetylcholine and increase in levels of acetylcholine. Side effects were also markedly different in the time of appearance, duration and severity. These results suggest that there are significant differences in the mechanisms of action of various cholinesterase inhibitors. Since all three cholinesterase inhibitors are currently used in the experimental treatment of Alzheimer's disease, these findings have potential implications for the symptomatic therapy of these patients.

Acetylcholine↗

PubMed1987

Pharmacokinetics and pharmacodynamics of physostigmine after intravenous administration in beagle dogs.

The time course of physostigmine (Phy), its metabolites and activity of cholinesterase (ChE) in plasma were studied after intravenous bolus administration of [3H]Phy (100 micrograms/kg) to beagle dogs. The maximal inhibition of ChE (78%) in plasma at 2 min correlated with the largest concentration of physostigmine (124 ng/ml). The concentration of physostigmine decreased by 88% to 16 ng/ml at 45 min when the activity of ChE was still 59% inhibited. Acetylcholinesterase activity in four regions of the brain (medulla, striatum, cerebellum and cortex) was not significantly different from controls at 70 +/- 5 min after administration of physostigmine. Concentrations of physostigmine and its metabolites determined by HPLC were not significantly different in different regions. In plasma, physostigmine was found, together with eseroline and two other metabolites M1 and M2. At 45 min, only 18% of total radioactivity was due to physostigmine and 52% was due to the major metabolite M1. On the contrary, in regions of the brain, metabolite M1 represented only 1.9-3.37% of total radioactivity at 70 +/- 5 min. Pharmacokinetic parameters, obtained in the dog, were compared to previously published data in rat and man. The elimination half-life (beta) was 30.7 min in the dog as compared to 15 min in rat and and 21.7 min in man. The Vd (ml/kg) was higher than total body water volume in all three species: dog (1832), rat (1352) and man (664), indicating sequestration of the drug in body compartments. Clearance (ml/min/kg) was found to be 41.2 in dog, which compares to 62 in rat and 22 in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

A comparison of the effects of two inhibitors on brain cholinesterase.

In the present paper various routes of administration (i.m., i.v. and i.c.v.) of physostigmine are compared and the effect of two drugs producing inhibition of cholinesterase, physostigmine and metrifonate, on the activity of cholinesterase in the brain of the rat and on levels of acetylcholine (ACh) and choline (Ch). After intramuscular administration of physostigmine (500 micrograms/kg), the activity of cholinesterase in brain was maximally inhibited (76%) at 5 min and recovered to 50% at 40 min. At 5 min, areas of the brain such as the striatum and medulla oblongata showed 49 and 67% inhibition, respectively. Levels of physostigmine in brain peaked at 5 min (1.28 nmol/g). With the exception of the cerebellum, there was a direct correlation between the concentration of physostigmine and inhibition of cholinesterase in a given area. With the intravenous route of administration (100 micrograms/kg), the activity of cholinesterase in brain was maximally inhibited (67%) at 3 min and recovered to 50% at 12 min. At 60 min, the activity of cholinesterase was 90% of control. Levels of physostigmine in brain peaked at 2 min (0.47 nmol/g). At 15 min, with intraventricular administration (4 micrograms), the activity of cholinesterase was 73% and 31% inhibited in the hippocampus and striatum, respectively. Other areas of brain showed intermediate values of inhibition. Levels of acetylcholine were increased 18 and 22% above control in the striatum and hippocampus, respectively and did not change in the medulla. After intramuscular administration of metrifonate (80 mg/kg), the activity of cholinesterase decreased to 26% at 30 min, recovered to 50% at 180 min and returned to 74% at 360 min. Levels of acetylcholine increased by 45% at 45 min, then returned to normal by 120 min. When metrifonate (2.5 mg) was given intraventricularly the activity of cholinesterase decreased in the left side injected at 30 min to 20% in hippocampus; 22% in the medulla; 50% in the cerebellum; 58% in the striatum and 72% in cortex. Levels of acetylcholine increased maximally at 45 min in hippocampus and cortex and peaked in the striatum at 60 min. The greatest increases were seen in the hippocampus and cortex with 60 and 55%, respectively. The results of this study reveal some major differences between the effects of the two substances in brain. Four major conclusions are apparent from this study. First, based on these results, it is concluded that metrifonate is more likely to produce a therapeutic effect in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1986

Relation of brain regional physostigmine concentration to cholinesterase activity and acetylcholine and choline levels in rat.

The relationship between physostigmine (Phy) concentration, acetylcholine (ACh), choline (Ch) and cholinesterase (ChE) activity was examined in whole rat brain after the administration of [3H]Phy (650 microgram/kg i.m.). Cholinesterase inhibition was found to be inversely related to Phy levels. Maximal inhibition (80%) was seen at 5 min and by 2 hrs ChE activity had returned to control levels. Acetylcholine levels in whole brain peaked at 30 min at a concentration (80 nmol/g) 2.3 times higher than controls (33 nmol/g). Choline levels were not significantly altered. The regional distribution of Phy concentration and ChE activity was studied in six areas of the brain following i.m. administration of three different dosages of ( 3H]Phy. Physostigmine concentration and ChE activity showed a dose dependency in each area examined except in SP (medial septum). Striatum (ST) showed the greatest relative increase of ACh up to 30 min, when compared to other areas. Choline levels were not changed in any area with the exception of ST at 5 min where a decrease was seen. There was a relationship between ChE activity, Phy concentration and ACh levels in all areas examined with exception of the medulla oblongata (MO). Our results indicate that even though ChE was inhibited practically uniformly in all brain areas, the percent increase with respect to control animals and the relative increase of ACh varied widely from area to area. This finding has clinical implications in cases in which cholinomimetic therapy is used to elevate ACh levels in specific brain areas which show a cholinergic deficit.

Acetylcholine↗

PubMed1986

The effects of physostigmine on acetylcholinesterase activity of CSF plasma and brain. A comparison of intravenous and intraventricular administration in beagle dogs.

The effects of various doses of physostigmine (Phy) on the activity of acetylcholinesterase (AChE) in plasma, cerebrospinal fluid (CSF) and brain were studied in beagle dogs. Two routes of administration were compared: intravenous (i.v.) and intracerebroventricular (i.c.v.). With intracerebroventricular administration, over 90% inhibition of the activity of AChE in CSF was reached within 5 min of injection at all doses (10-120 micrograms). Even at the smallest dose (10 micrograms), 50% inhibition of activity of the enzyme in CSF was still present at 90 min. The activity of AChE in plasma was only minimally inhibited by intraventricular administration of physostigmine. A different response was obtained following intravenous administration of physostigmine (250-1000 micrograms). The activity of AChE in plasma was inhibited but the activity of AChE in CSF was increased (36-80% at 180 min). This increase was dose-dependent and was blocked by pretreatment with atropine (1.5 mg i.v.) which suggests the involvement of a muscarinic receptor mechanism. The time course of the accumulation and regional distribution of [3H]physostigmine in brain also varied with the route of administration. At 5 min, with intravenous administration, physostigmine (1000 micrograms) reached greater concentrations and caused greater inhibition of AChE in the cortex. With intraventricular administration, physostigmine (80 micrograms) reached greater concentrations in two regions adjacent to the ventricular surface: the striatum and hippocampus. These regions also showed greater inhibition of the activity of AChE. Moderate to severe symptoms of cholinergic hyperactivity were seen only with the largest intraventricular dose (120 micrograms). This study suggests that intraventricular administration of physostigmine, a reversible inhibitor of cholinesterase (ChE), may offer distinct advantages over intravenous administration. Inhibition of acetylcholinesterase in CSF was more pronounced and persisted longer when physostigmine was administered directly into the CSF than when given intravenously. The implications of this study for a cholinergic therapy of Alzheimer's disease are discussed.

Acetylcholinesterase↗

PubMedDate not supplied

Maternal thyroid function does not alter maternal serum alpha-fetoprotein interpretation.

OBJECTIVE: Endocrine alterations of metabolism such as diabetes and obesity are known to affect maternal serum alpha-fetoprotein interpretation. Thyroid function has been questioned, e.g., because of binding globulins, but not adequately studied as to its impact upon maternal serum alpha-fetoprotein. The purpose of this study was to assess the possible effects of T4 and thyroid-stimulating hormone (TSH) on alpha-fetoprotein production, and to determine if thyroid function (hypothyroidism) alters maternal serum alpha-fetoprotein. METHODS: We evaluated maternal serum alpha-fetoprotein, T4, and TSH records of 25,551 patients, between 14 and 20 weeks' gestation, on whom both studies had been ordered by the patient's primary obstetrician to rule out maternal thyroid disease in pregnancy. Statistical analyses were performed by chi 2 and regression analysis. RESULTS: Patients were stratified according to thyroid function tests into two groups: hypothyroidism (T4 < 6.5 micrograms/dL and/or TSH > 5.0 micrograms/mL), and normal or hyperthyroidism (T4 > or = 6.5 micrograms/dL and/or TSH > or = 5.0 microU/mL). Maternal serum alpha-fetoprotein values were compared among groups for each gestational age. No significant variation or correlation of maternal serum alpha-fetoprotein and thyroid function was observed. CONCLUSIONS: Although other endocrine abnormalities are known to impact maternal serum alpha-fetoprotein values either through decreased production, decreased placental permeability, or plasma volume distribution alterations, maternal thyroid status does not interfere with proper interpretation of maternal serum alpha-fetoprotein.

Female↗

PubMedDate not supplied

Induction of labor in patients with term premature rupture of membranes. Effect on perinatal outcome.

OBJECTIVE: To determine whether delayed induction of labor in patients with premature rupture of membranes (PROM) at term has beneficial effects on the mother or the infant. STUDY DESIGN: Retrospective analysis of our database revealed 576 patients >37 weeks of gestation with PROM, who delivered live-born infants without major congenital anomalies. We analyzed the frequencies of primary cesarean, neonatal intensive care unit (NICU) admissions, and oxytocin use by time since hospital admission and interval until onset of labor. RESULTS: NICU admission increased from 1.9% in <3 h between admission to onset of labor to 13.3% after >18 h. Admission-onset of labor interval, birth weight of <2,500 or >4,000 g and meconium were all more important determinants of NICU admission than gestational age, duration of labor, PROM, and ROM. Prolonged admission-onset of labor interval was associated with an increased risk of variable decelerations (p < 0.001). Primary cesarean rates increased progressively with longer intervals between admission and onset of labor. Stepwise discriminant function analysis revealed that labor duration, admission-onset of labor interval, gestational age, and birth weight of <2,500 g were all more important determinants of primary cesarean delivery than the durations of PROM or ROM. CONCLUSIONS: The increased frequencies of NICU admission, variable decelerations, and primary cesarean suggest that delayed labor induction after hospital admission was linked to worsened perinatal outcomes. These results may have been influenced by usually performing a single digital examination as part of initial evaluation of term patients who present with PROM. Based on our data, we suggest immediate induction for PROM at term, especially if digital examination has been performed.

Adult↗

PubMedDate not supplied

Severe oligohydramnios with intact membranes: an indication for diagnostic amnioinfusion.

OBJECTIVE: To quantify the improvement in ultrasonographic fetal imaging following diagnostic amnioinfusion for the indication of unexplained midtrimester oligohydramnios. METHODS: Patients referred for unexplained midtrimester oligohydramnios were retrospectively reviewed. Videotapes of those undergoing diagnostic antenatal amnioinfusion were analyzed for quality of visualization of routinely imaged structures before and after the infusion procedure. RESULTS: The overall rate of adequate visualization of fetal structures improved from 50.98 to 76.79% (p < 0.0001). In fetuses having preinfusion-identified obstructive uropathy, there was improvement in identification of associated anomalies from 11.8 to 31.3%. CONCLUSIONS: Several authors have suggested that diagnostic amnioinfusion can facilitate fetal imaging and increase diagnostic precision in the setting of unexplained severe oligohydramnios. We have quantified the improvement in the rate of optimal visualization of fetal structures which likely translates, in experienced hands, into this observed improved diagnostic precision. Of particular importance is the improvement in appreciation of associated anomalies in cases of obstructive uropathy in which such findings may determine whether or not invasive fetal therapy is indicated.

Abnormalities, Multiple↗

PubMedDate not supplied

Uterine artery Doppler velocimetry in patients with idiopathic hydramnios.

OBJECTIVE: To evaluate the role of overdistended uterus on the uterine artery (UA) blood flow velocimetry by comparing UA Doppler in patients with idiopathic hydramnios to patients with normal amniotic fluid (AF) volume. METHODS: Pulsatility index (PI) of both UAs was determined prospectively between 26 and 41 weeks of gestation in 72 consecutive pregnant women with singleton pregnancies and idiopathic hydramnios and in 72 pregnant women with normal AF volume. Hydramnios was defined as an AF index (AFI) above 24 cm. A normal amount of AF was defined as an AFI of 6-24 cm. Patients with known fetal structural or chromosomal anomalies and those with diabetes mellitus were excluded. RESULTS: No significant differences were observed between the groups with regard to maternal age, gravidity, and gestational age at examination. Gestational age at delivery and accordingly birth weight were significantly lower in patients with hydramnios compared to those with a normal AFI (34.9 +/- 2.1 vs. 39.1 +/- 1.2, p < 0.001; 2,508 +/- 399 vs. 2,995 +/- 420, p < 0.001, respectively). No significant differences were noted between right UA PI (0.73 +/- 0.3 in the hydramnios group vs. 0.71 +/- 0.2 in the control group; p = 0.091) and left UA PI (0.91 +/- 0.3 in the hydramnios group vs. 0.84 +/- 0.3 in the control group; p = 0.131) of both groups. CONCLUSION: UA velocimetry in patients with idiopathic hydramnios was not significantly different from those with a normal AF volume.

Adult↗

PubMedDate not supplied

Effects of intra-amniotic meconium exposure on the fetal rat: development of a pathogenic model.

OBJECTIVE: To develop an in vivo animal model for the study of the effects of intrauterine meconium exposure on the fetus. METHODS: Timed pregnant Long-Evans rats were purchased on gestational day (GD) 12 and allowed to acclimate for at least 48 h prior to surgery. Laparotomy was performed and both uterine horns were exteriorized through the abdominal incision. A 26-gauge needle was used to inject either 0.1-cm(3) sterile normal saline or a 20% meconium suspension into each individual gestational sac. The uterus was returned to the abdomen and the incision was closed. On GD 21 (term = 21 days) a cesarean section was completed and the number and viability of fetuses in each horn were recorded. RESULTS: A total of 14 animals were involved in this pilot study. One rat underwent sham surgery with only intra-amniotic saline injection and 13/15 fetuses survived to term. Two animals that underwent surgery on day 18 expired < 24 h postinjection. Eleven maternal animals were injected on GD 20 and underwent cesarean delivery at term; survival rates for saline-injected animals were 71.2% compared to 66.2% for meconium-exposed fetuses. CONCLUSION: We have established an in vivo animal model that allows for the examination of the effects of prolonged intrauterine meconium exposure on the fetus.

Amniotic Fluid↗

PubMedDate not supplied

Subjective ultrasonographic assessment of amniotic fluid depth: comparison with the amniotic fluid index.

The purpose of this study was to evaluate the ability to identify abnormalities in amniotic fluid volume by subjective ultrasonographic assessment compared to a semiobjective method. In 886 consecutive ultrasound examinations subjective assessment of the amniotic fluid volume was performed and graded into 3 categories: normal, decreased, and increased. Following that, a four-quadrant sum (amniotic fluid index) was performed by the same experienced ultrasonographer and divided into 3 categories using the 5th and 95th percentiles. The sensitivity of the subjective analysis to diagnose a decreased amniotic fluid volume when compared with the amniotic fluid index was 58% (95% confidence interval, CI: 40-70%), with a false-positive rate of 17% (CI 8-32%). The sensitivity of the subjective analysis to diagnose an increased amniotic fluid volume when compared with the amniotic fluid index was 100% (CI 70-100%). However, the false-positive rate was 74% (CI 55-85%). Diagnosis of a normal amount of amniotic fluid by the subjective technique had a sensitivity of 96% (CI 95-97%) and a false-positive rate of 3% (CI 2-4%). Subjective ultrasonographic assessment of the amniotic fluid volume may serve as a screening test for the experienced ultrasonographer. However, when a decreased or increased amount of amniotic fluid volume is suspected, one may elect to use the amniotic fluid index for confirmation of the subjective impression.

Amniotic Fluid↗

PubMedDate not supplied

Maternal serum alpha-fetoprotein screening: the need to use race/ethnic specific medians in Asians.

OBJECTIVES: We questioned whether race-specific databases for maternal serum alpha-fetoprotein (MSAFP) screening should be added to those already available for African-American and white patients. STUDY DESIGN: We analyzed 138,272 MSAFP samples. The geographic origin of the samples was New York metropolitan area. Patients were classified as white, African-American, Hispanic or Asian. The usual adjustments were made and groups compared. Statistical analysis included ANOVA and multiple comparison test. RESULTS: MSAFP values are highest (p < 0.05) for Asians, followed by African-Americans, Hispanics, and whites, although the difference between Hispanic and white was not significant. CONCLUSIONS: Four separate databases are definable if specimen quantity is sufficient. Race/ethnic specific databases are more likely to yield the most accurate detection of abnormal MSAFP values, and therefore, fetal anomalies.

Asian↗

PubMedDate not supplied

Ultrasound-detected free-floating particles in amniotic fluid: correlation with maternal serum alpha-fetoprotein.

The objective of this study was to determine the rate of ultrasound-detected free-floating particles in amniotic fluid during the early second trimester and their relationship with maternal serum alpha-fetoprotein (MSAFP) in patients with normal amniotic fluid alpha-fetoprotein (AFAFP). Ninety-eight consecutive patients undergoing second-trimester amniocentesis for various indications were prospectively studied. Before undergoing amniocentesis, each patient had a level II ultrasound examination and evaluation of the presence of free-floating particles. A subjective estimate of the particle amount and measurement of the size of the largest particle seen were made. Patients were stratified into three groups according to their MSAFP level (low, normal, high). Statistical significance of results was assessed by analysis of variance and multiple comparison procedure, and by nonparametric procedures, as appropriate. MSAFPs (mean +/- 1 SD) were 0.41 +/- 0.18 and 4.88 +/- 2.22 multiples of the median for the low and the high groups, respectively. All AFAFPs were within normal limits. Ninety-four percent of patients with high MSAFP had free-floating particles in amniotic fluid as compared to 43% in the low and normal groups (p < 0.01). Patients with high MSAFP had significantly greater density and size of particles. The presence of ultrasound-detected free-floating particles in amniotic fluid of normal patients during the early second trimester may preclude its use as a reliable indicator for fetal lung maturity, or suggest that the source of these particles may differ by trimester. High MSAFP is significantly correlated with the ultrasonographic appearance of free-floating particles, as well as with larger size and higher amount.

Adult↗

PubMedDate not supplied

Technical aspects of transcervical chorionic villus sampling.

Following the 1990 FDA approval of the Trophocan catheter for use in transcervical chorionic villus sampling (CVS), an increasing number of US physicians have begun offering the procedure. To obtain privileges to perform CVS, some states such as California have enacted legislation requiring the performance of a certain number of CVS procedures in pregnancies in which the patient has already chosen first-trimester abortion. This practice is not universally feasible for legal, logistic, or financial reasons. We describe our approach to training in a busy reproductive genetics service. The physician initially trains by performing amniocentesis to optimize skills in ultrasound-directed needle guidance and placement. During this initial period, he or she also assists in performing transabdominal CVS procedures. The initial transcervical CVS cases should be performed in those situations requiring minimal catheter manipulation, or in those individuals undergoing CVS in the setting of spontaneous abortion. Cases of increasing difficulty should only be performed as skill and familiarity increase. For a physician already skilled and experienced in ultrasound-guided invasive procedures, sequential periods of observation at a busy center allows him or her to become familiar with the common pitfalls in performing transcervical CVS, and thus avoid them. Using this approach, we have performed over 5,000 CVS procedures and trained 6 reproductive genetics fellows in transcervical CVS.

Cervix Uteri↗

PubMedDate not supplied

Fetal liver function tests: umbilical cord gamma-glutamyltransferase as a marker for fetal abnormality.

The objective was to assess the association of fetal liver function tests in various (noninfectious) abnormal fetal conditions. Liver function tests and complete blood counts were evaluated in 72 consecutive fetal blood specimens obtained by cordocentesis. The indications for cordocentesis included: fetal malformation (24), red blood cell alloimmunization (23), possible fetal infection (17), oligohydramnios (5), and immunologic thrombocytopenic purpura (3). Statistical analysis included analysis of variance and linear regression analysis. Liver function tests including total protein, albumin, total bilirubin, alanine and aspartate aminotransferase were all within the range of previously published normal values. However, fetal gamma-glutamyltransferase levels (mean +/- SEM) were 157.1 +/- 15.1 IU/l (norm: 24.4 +/- 1.2 IU/l; p < 0.001). There were no statistically significant differences in the gamma-glutamyltransferase levels between the various groups of fetal abnormalities. Mean fetal gamma-glutamyltransferase levels in 8 normal fetuses were 106.2 +/- 17.5 IU/l. In conclusion, fetal gamma-glutamyltransferase levels are significantly elevated in several abnormal fetal conditions.

Blood Cell Count↗

PubMedDate not supplied

Indomethacin and fetal ductus arteriosus: complete closure after cessation of prolonged therapeutic course.

Indomethacin is a very effective tocolytic agent. However, concern about its possible constrictive effect on fetal ductus arteriosus has limited the use of this medication in pregnancy. A 29-year-old woman was treated with indomethacin at 27 weeks of gestation for preterm labor and polyhydramnios. She received a dose of 75 mg/day for 5 weeks. At 35 weeks of gestation, she had a cesarean delivery due to fetal distress, and a hydropic baby was delivered. The infant died shortly after. Nonimmune hydrops fetalis and closed ductus arteriosus were the only pathological findings at autopsy. In utero, irreversible, complete closure of the ductus arteriosus is very rare. In the case presented, prolonged use of indomethacin during pregnancy was associated with complete closure of the ductus arteriosus that developed most probably after discontinuation of therapy. This case emphasizes the need for frequent fetal echocardiography examinations during as well as after maternal indomethacin treatment.

Adult↗

PubMedDate not supplied

Fetal rat brain injury: effect of transient maternal hypoxemia.

OBJECTIVE: To determine whether transient acute maternal hypoxemia during the end of pregnancy may cause neuronal damage in fetal rat brains. STUDY DESIGN: Nine pregnant rats (4 study and 5 controls) at 16-17 gestational days were studied. The study rats were placed in a chamber and breathed a gas mixture of 11.8% oxygen, 4.95% CO2, and nitrogen for either 1 or 2 h, while the control animals breathed room air. Tail venous blood was collected and gases were evaluated at the beginning and conclusion of the exposure periods. After 72 h of recovery, at 19-20 days' gestation, the fetal cardiovascular systems were perfused with saline and formalin. The brains were embedded in paraffin, sectioned in coronal plane, and stained with hematoxylin and eosin Histologic assessment of sections was performed by a neuropathologist blinded to the protocol. Statistical analysis of the data was performed using analysis of variance and the chi-square test. RESULTS: Exposure to the gas mixture resulted in decreased maternal pO2 from 39.9 +/- 7.6 mm Hg in the control group to 28.8 +/- 2.0 mm Hg in the 2-hour hypoxia group (p < 0.05). No significant changes in maternal pH or pCO2 status have been noted. A total of 34 fetal rat brains served as controls and 26 brains as the hypoxia study group There was a significant increase in isolated neuronal damage, including necrosis and shrinkage of cells, with karyorrhexis (fragmentation and breakage of the nucleus) in the hippocampus, basal ganglia, thalamus, and hypothalamus in the hypoxemia rats as compared with controls. CONCLUSION: Transient maternal hypoxemia may cause neuronal necrosis in vulnerable regions of the fetal rat brain, including the hippocampus, basal ganglia, thalamus, and hypothalamus.

Animals↗

PubMedDate not supplied

Magnesium sulfate treatment decreases N-methyl-D-aspartate receptor binding in the rat brain: an autoradiographic study.

OBJECTIVE: We determined the effect of peripherally administered magnesium sulfate on N-methyl-D-aspartate (NMDA) receptor binding capacity in various regions of the rat brain. METHODS: Three separate experiments were performed. 1) Six rats were injected intraperitoneally with 270 mg/kg of magnesium sulfate, followed by 27 mg/kg every 20 minutes for 4 hours; controls (n = 6) received saline. 2) Six rats received intraperitoneal injections of magnesium sulfate (270 mg/kg) every 4 hours for 24 hours, while six received saline. 3) Six rats received intraperitoneal magnesium sulfate (270 mg/kg) every 12 hours for a total of 2 weeks, and six received saline. Rats were subsequently perfused and sacrificed, and their brains were dissected, rinsed, and frozen. Cryostat sections were taken, labeled by in vitro [3H]-CGP 39653, assayed autoradiographically, and mounted on Ultrofilm for 4 weeks. Optical density measurements of binding on each section were performed using an image analyzing system. Eleven brain regions were sampled: 1, 2) frontal and occipital cortex; 3-7) hippocampus--CA-1, CA-3, stratum radiatum, stratum oriens, dentate gyrus; 8) thalamus; 9) hypothalamus; 10) caudate nucleus; and 11) cerebellum. RESULTS: The NMDA receptor binding density in the hippocampus was significantly higher than in all other brain regions in all three experiments. In experiment 1, there was no significant effect on NMDA receptor binding. However, prolonged systemic administration of magnesium sulfate for 24 hours resulted in significantly reduced [3H]-CGP binding in all brain regions sampled. After chronic magnesium sulfate administration (2 weeks), the [3H]-CGP binding was still reduced in the cortex and some regions of the hippocampus; however, there was no significant change in other regions. CONCLUSIONS: Peripheral treatment with magnesium sulfate results in a significant reduction in the NMDA receptor binding capacity in the rat brain. These results support the hypothesis that magnesium central activity is mediated, at least in part, via the NMDA receptor.

Animals↗