Biomedical subjects

James N Reynolds

Publications and source records attributed to James N Reynolds.

7 recordsLinked to original sources

PubMed2003

Temporal profile of tissue plasminogen activator (tPA) and inhibitor expression after transient focal cerebral ischemia.

Altered tPA expression may influence the fate of neurons after cerebral ischemia. We determined the changes in tPA and plasminogen activator inhibitor (PAI-1) expression in adult rat brain after transient middle cerebral artery (MCA) occlusion. Immunohistology revealed tPA staining in ipsilateral but not contralateral cortex and striatum 6 h after occlusion. This pattern was maintained at 24 h. Staining data was supported by Western blot data which showed no tPA protein in contralateral cortex at 3 h but abundant protein in ipsilateral cortex which increased further at 6 h and 24 h. In contrast there was prominent PAI-1 immunostaining and protein expression in control tissue after MCA occlusion but it diminished progressively at 3, 6 and 24 h in the lesioned cortex.

Animals↗

PubMed2003

Effects of chronic prenatal ethanol exposure on NMDA receptor number and affinity for [3H]MK-801 in the cerebral cortex of the young postnatal and adult guinea-pig.

The objective of this study was to test the hypothesis that chronic prenatal ethanol exposure (CPEE) produces changes in the number and/or affinity of N-methyl-D-aspartate (NMDA) receptors in the cerebral cortex that are developmental-age-dependent. Timed, pregnant Dunkin-Hartley-strain guinea-pigs received oral intubation of one of the following regimens, given daily as two equally divided doses 2 h apart, from gestational day (GD) 2 to GD 67 (term, ~GD 68): (i) 4 g ethanol kg(-1) maternal bodyweight; (ii) isocaloric sucrose with pair feeding; or (iii) water. Maternal blood ethanol concentration was measured on GD 57 or 58 at 1 h after the daily dose, and was 51.1 +/- 8.5 mM (235 +/- 39 mg dL(-1); n = 8). At postnatal day (PD) 11 (pre-weaning) and PD 61 (adulthood), body, brain and cerebral cortical weights of the offspring were measured. The number of NMDA receptors and their affinity for [(3)H]MK-801 were measured in a crude cerebral cortical membrane preparation using saturation isotherm analysis to determine the B(max) and K(D). Chronic prenatal ethanol exposure decreased offspring brain and cerebral cortical weights at PD 11 and PD 61. At PD 11, there was no CPEE-induced change of [(3)H]MK-801 binding characteristics in the cerebral cortex. At PD 61, both B(max) and K(D) for [(3)H]MK-801 binding to cerebral cortical NMDA receptors were decreased by CPEE compared with the isocaloric sucrose/pair-fed and water treatment groups. Loss of cerebral cortical NMDA receptors and increased affinity of the remaining receptors for [(3)H]MK-801 in the adult guinea-pig, compared with no change in the number or affinity of these receptors in the young postnatal offspring, demonstrated that the effects of CPEE on these ionotropic glutamate receptors are developmental-age-dependent.

Animals↗

PubMed2003

Chronic prenatal ethanol exposure alters ionotropic glutamate receptor subunit protein levels in the adult guinea pig cerebral cortex.

BACKGROUND: The superfamily of glutamate-gated ion channels mediates fast excitatory synaptic transmission in the central nervous system and is composed of the NMDA, AMPA, and kainate receptors. Binding studies have shown that chronic prenatal and/or neonatal ethanol exposure produces persistent effects on the numbers of some of these channels. However, whether or not this chronic ethanol exposure produces long-lasting effects on the expression of specific ionotropic receptor subunits remains an open question. METHODS: Timed pregnant Dunkin-Hartley strain guinea pigs received oral administration of one of the following regimens between gestational days 2 and 67: (1) 4 g of ethanol per kilogram of maternal body weight per day with ad libitum access to pellet food and water (ethanol group), (2) isocaloric sucrose- and pair-feeding with ad libitum access to water (sucrose group), or (3) isovolumetric water with ad libitum access to food and water (water group). The maternal blood ethanol concentration produced by the ethanol regimen was 71 +/- 12 mM. Adult offspring were killed on postnatal day 61, and cerebral cortical tissue was analyzed for ionotropic glutamate receptor subunit expression by Western immunoblotting. RESULTS: There was a statistically significant decrease in NR2B subunit protein expression and an increase in GluR2/3 subunit protein expression in the ethanol group. Expression of NR1, NR2A, NR2C, GluR1, GluR6/7, and KA2 subunit proteins was not affected. CONCLUSIONS: These results demonstrate that chronic prenatal ethanol exposure produces long-lasting effects on the subunit composition of NMDA and AMPA receptors in the cerebral cortex of the adult guinea pig.

Animals↗

PubMed2003

Chronic prenatal ethanol exposure-induced decrease of guinea pig hippocampal CA1 pyramidal cell and cerebellar Purkinje cell density.

The brain is a key target of ethanol teratogenicity, in which ethanol can produce neurodegeneration in selected areas, including the hippocampus and cerebellum. The research objective was to test the hypothesis that chronic prenatal ethanol exposure, via maternal ethanol administration, produces differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells. Timed pregnant guinea pigs received chronic oral administration of ethanol, isocaloric-sucrose/pair-feeding, or water throughout gestation (term, about gestational day (GD) 68), and the offspring were studied at GD 62 (near-term fetus), postnatal day (PD) 1 (neonate), PD 5, and PD 12 (early postnatal life). Ethanol treatment, compared with isocaloric-sucrose/pair-feeding and water treatments, decreased brain, hippocampal, and cerebellar weights at GD 62, PD 1, PD 5, and PD 12. Hippocampal CA1 pyramidal cell linear density and cerebellar Purkinje cell linear density were unaffected at GD 62. Ethanol treatment produced 25, 30, and 30% decreases in linear density of hippocampal CA1 pyramidal cells at PD 1, PD 5, and PD 12, respectively, and a 30% decrease in linear density of cerebellar Purkinje cells at PD 12 only. At PD 5, Purkinje cell profile linear density remained unaffected; however, ethanol treatment appeared to increase linear density of apoptotic Purkinje cell nuclei, as determined by a modified TUNEL method. The data demonstrate that chronic prenatal ethanol exposure produces apparent differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells in the developing guinea pig.

Administration, Oral↗

PubMed2002

Neuroprotection against ischemic brain injury conferred by a novel nitrate ester.

Nitrates exhibit a selectivity of action in different tissue types not fully recognized: in particular, the neuromodulatory and cardiovascular properties can be dissociated. A novel nitrate showed relatively weak systemic effects, but in the middle cerebral artery occlusion rat model of focal ischemia, reduced the cerebral infarct by 60-70% when administered 4 h after the onset of ischemia.

Animals↗

PubMed2002

Inhibition of lipid peroxidation in synaptosomes and liposomes by nitrates and nitrites.

NO is produced endogenously from arginine by the action of NO synthase, and exogenously by nitrovasodilators, including organic nitrates and nitrites. NO has been proposed as a cytotoxic and cytoprotective agent. There is strong evidence that NO acts as an apparent antioxidant in inhibiting lipid peroxidation, via chain termination, and interestingly lipid nitrates and nitrites have been proposed to be products of this chain termination. Both pro- and antioxidant mechanisms may be drawn for nitrates and nitrites; therefore, their effects on lipid peroxidation were measured in two systems, using tocopherol, thiol, and an NO donor for comparison: (1) rat cerebrocortical synaptosomes with Fe(II)-induced lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS), and (2) phospholipid liposomes with an azo-initiator induction system, quantified by a fluorescent probe of peroxide formation. In contrast to the classical nitrate nitroglycerin, novel nitrates which release NO on reaction with thiols and two novel nitrates which spontaneously generate NO in aqueous solution inhibited lipid peroxidation. i-Amyl nitrite inhibited lipid peroxidation, and its properties were further studied with ESR spectroscopy. The data show that classical nitrites and novel nitrates are not prooxidants, but inhibit lipid peroxidation.

Amyl Nitrite↗

PubMedDate not supplied

Brain growth spurt-prenatal ethanol exposure and the guinea pig hippocampal glutamate signaling system.

This study tested the hypothesis that prenatal ethanol exposure (PEE) during the brain growth spurt (BGS) in the guinea pig suppresses the glutamate-NMDA receptor-nitric oxide synthase (NOS) signaling system in the developing hippocampus. Pregnant guinea pigs [term, about gestational day (GD) 68] received daily oral administration of 2 g ethanol/kg maternal body weight/day on GD 43 and/or GD 44 and then 4 g ethanol/kg maternal body weight/day from GD 45 to GD 62, isocaloric-sucrose/pair-feeding or water. Offspring were studied at GD 63 (near-term fetus) and postnatal day (PD) 10 (young postnatal life). Maternal blood ethanol concentration during ethanol treatment, pregnancy outcome variables, no change in spontaneous locomotor activity, and decreased brain and cerebral cortical weight data were reported previously [Neurotoxicol. Teratol. 23 (2001) 355]. This BGS-PEE regimen did not affect hippocampal stimulated glutamate release in young postnatal offspring, NMDA receptors as assessed by [3H]MK-801 binding, or NOS activity in near-term fetal offspring. Furthermore, BGS-PEE did not affect the number of hippocampal CA1 and CA3 pyramidal cells and dentate gyrus granule cells in defined locations of these three regions in the hippocampal formation. These findings are in contrast to the effects of chronic prenatal exposure to this ethanol regimen throughout gestation, including suppression of the hippocampal glutamate-NMDA receptor-NOS signaling system, decreased number of hippocampal CA1 pyramidal cells, increased spontaneous locomotor activity, and impaired performance in the Morris water maze.

Animals↗