The effects of magnesium sulfate on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats

The study was performed to evaluate whether magnesium sulfate could alter the degree of disruption of the blood-brain barrier (BBB) caused by hyperosmotic mannitol. Wistar adult female rats were infused with 25% mannitol into the left internal carotid artery. Each animal received intraperitoneally a 300 mg/kg loading dose of magnesium sulfate, dissolved in 0.9% saline, followed by a further 100 mg/kg dose. In the other group, intracarotid infusion of magnesium sulfate was performed at a dose of 150 mg/kg 10 min before mannitol administration. Evans blue (EB) dye was used as a marker of BBB disruption. The measured serum glucose and magnesium levels increased after mannitol and/or magnesium administration when compared with their initial values before treatment (P < 0.01). Water content of the left hemisphere was significantly increased by hyperosmotic mannitol (P < 0.01). The increased water content in the mannitol-perfused hemisphere was significantly decreased by magnesium treatment (P < 0.05). The content of EB dye in the mannitol-perfused hemisphere markedly increased when compared with the right hemisphere of the same brain (P < 0.01). The EB dye content in the mannitol-perfused hemisphere following both intraperitoneal and intraarterial administration of magnesium decreased when compared with mannitol alone (P < 0.01). We conclude that although magnesium sulfate administration by both intracarotid arterial and intraperitoneal routes attenuates BBB disruption caused by hyperosmolar mannitol, particularly intraperitoneal route of magnesium sulfate administration may provide a useful strategy to limit the transient osmotic opening of the BBB.     

Cyclic Nucleotide Response of the Hippocampal Formation to Septal Stimulation in Naive and Kindled Rats

Rats were kindled through nonmagnetic electrodes stereotaxically implanted into the medial septum. Concentrations of cyclic AMP and cyclic GMP were measured by radioimmunoassay in seven brain regions after microwave fixation during the development and expression of kindled seizures. Hippocampal concentrations were similar to untreated controls (cyclic GMP level in the left and right hippocampus, 0.66 +/- 0.04 and 0.68 +/- 0.07 pmol/mg of protein, respectively; cyclic AMP, 9.4 +/- 0.9 and 9.6 +/- 0.8 pmol/mg of protein, respectively), in kindled animals that were not stimulated, and in naive animals in response to septal stimulation, in spite of the presence in the latter group of bilateral hippocampal afterdischarges. Animals that failed to develop kindling and kindled animals that failed to have a seizure in response to stimulation also showed no change in cyclic nucleotide concentrations in any brain region. Kindled animals that developed a seizure following stimulation showed significant elevations in levels of both cyclic GMP and cyclic AMP in hippocampus and in several other brain regions. A single naive animal that had a seizure in response to its first stimulation also appeared to have elevated concentrations of both cyclic nucleotides in hippocampus. These data suggest that the elevation in levels of both cyclic GMP and cyclic AMP during kindled seizures is associated with seizure development rather than with the generation of afterdischarges or with the kindling engram.     

Comparative angioprotective effects of magnesium compounds

Magnesium (Mg) deficiency is implicated in the development of numerous disorders of the cardiovascular system. Moreover, the data regarding the efficacy of different magnesium compounds in the correction of impaired functions due to low magnesium intake are often fragmentary and inconsistent. The aim of this study was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate, Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days. A low Mg diet decreased the Mg concentration in the plasma and erythrocytes, which was accompanied by a reduced concentration of eNOs and increased levels of endothelin-1 level in the serum and impaired endothelium-dependent vasodilatation. These effects increased the concentration of proinflammatory molecules, such as VCAM-1, TNF-α, IL-6 and CRP, indicating the development of systemic inflammation and endothelial dysfunction. The increased total NO level, which estimated from the sum of the nitrate and nitrite concentrations in the serum, may also be considered to be a proinflammatory marker. Two weeks of Mg supplementation partially or fully normalised the ability of the vascular wall to effect adequate endothelium-dependent vasodilatation and reversed the levels of most endothelial dysfunction and inflammatory markers (except CRP) to the mean values of the control group. Mg sulphate had the smallest effect on the endothelin-1, TNF-α and VCAM-1 levels. Mg N-acetyltaurate was significantly more effective in restoring the level of eNOS compared to all other studied compounds, except for Mg oxybutyrate. Taken together, the present findings demonstrate that all Mg compounds equally alleviate endothelial dysfunction and inflammation caused by Mg deficiency. Mg sulphate tended to be the least effective compound.     

Anticonvulsant effects of the 3-hydroxyanthranilic acid dioxygenase inhibitor NCR-631

Summary. The kynurenine pathway intermediate 3-hydroxyanthranilic acid (3-HANA) is converted by 3-HANA 3,4-dioxygenase (3-HAO) to the pro-convulsive excitotoxin quinolinic acid. In the present study, the anticonvulsant effect of the 3-HAO inhibitor NCR-631 was investigated in models of chemically- and sound-induced seizures. Administration of NCR-631 i.c.v. at a dose of 300 nmol in Sprague-Dawley rats was found to prolong the latency of occurrence of pentylenetetrazole (PTZ)-induced seizures. Also systemic pre-treatment with NCR-631 s.c. in N.M.R.I. mice subjected to PTZ-induced seizures provided an increase in the latency until onset of seizures, concomitant with a reduction in the severity of the seizures. However, the anticonvulsant effect of NCR-631 was short lasting (15–30 min), and only observed at a dose of 250 mg/kg. A similar dose- and time-dependent anticonvulsant effect of NCR-631 was found in seizure-prone DBA/2J mice following sound-induced convulsions. Hence, the findings show that NCR-631 has anticonvulsant properties against generalized tonic-clonic seizures of different origin, suggesting that it may constitute a useful tool to study the role of kynurenines in various convulsive states. Received August 31, 1999 Accepted September 20, 1999     

Effect of magnesium sulfate in oxidized lipid bilayers properties by using molecular dynamics

Magnesium sulfate (MgSO₄) has been used as a protector agent for many diseases related to oxidative stress. The effect of MgSO₄ on the oxidized lipid bilayer has not yet been studied using molecular dynamics calculations. In this work, the effects of oxidation were evaluated by using a POPC membrane model at different concentrations of its aldehyde (-CHO) and hydroperoxide (-OOH) derivatives with and without MgSO₄. Several quantitative and qualitative properties were evaluated, such as membrane thickness, area per lipid, area compressibility modulus, snapshots after simulation finish, density distributions, time evolutions of oxidized group positions, and radial distributions of oxidized group concerning Mg. Results indicate that in the absence of MgSO₄ the mobility of oxidized groups, particularly –CHO, toward the surface interface is high. At a low oxidation level of the bilayer there is an increase in the compressibility modulus as compared to the unoxidized bilayer. MgSO₄, at a low oxidation level, tends to lessen the oxidation effects by lowering the dispersion in the distribution of oxidized species toward the membrane surface and the water region. However, MgSO₄ does not change the trends of decreasing membrane thickness and area compressibility modulus and increasing area per lipid upon oxidation. In this regard, MgSO₄ diminishes the electrostatic long-distance attractive interactions between the oxidized groups and the charged headgroups of the interface, owing to the Mg⁺² and SO₄^-2 screening effects and an electrostatic stabilization of the headgroups, preventing the pore formation, which is well-known to occur in oxidized membranes.     

Somatostatin release in the hippocampus in the kindling model of epilepsy: a microdialysis study

Somatostatin biosynthesis in the hippocampus is activated during and following kindling epileptogenesis. The aim of this study was to investigate whether this phenomenon is associated with enhanced somatostatin release in vivo. Experiments have been run in awake, freely moving rats, implanted with a bipolar electrode in the right amygdala (for kindling stimulation), and with a recording electrode and a microdialysis probe in the left hippocampus. Basal somatostatin-like immunoreactivity (-LI) release was significantly greater in kindled than naive rats. In naive rats, a 2-min perfusion with 100 mM K(+) did not affect behavior and EEG recordings and nonsignificantly increased somatostatin-LI release; a 10-min K(+) perfusion evoked numerous wet dog shakes, electrical seizures (class 0; latency congruent with 8 min, duration congruent with 8 min), and somatostatin-LI release ( congruent with 350% of basal); and a single kindling after-discharge (4 +/- 3-s duration in the hippocampus) also evoked somatostatin-LI release ( congruent with 200% of basal). In kindled rats, a 2-min 100 mM K(+) perfusion evoked hippocampal discharges in three of seven animals (latency congruent with 2 min, mean duration congruent with 1.5 min) and increased somatostatin-LI release ( congruent with 250% of basal); a 10-min K(+) perfusion evoked behavioral seizures (class 1 to 5, latency congruent with 4 min, mean duration congruent with 12 min) with numerous wet dog shakes and robust somatostatin-LI release ( congruent with 350% of basal); and a kindling stimulation evoked generalized seizures (class 4 or 5, 77 +/- 15-s duration in the hippocampus) with remarkable somatostatin-LI release ( congruent with 300% of basal). These data demonstrate that hippocampal somatostatin release is increased in the kindling model in vivo.     

The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats

Background

Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring.

Methods

Forty timed-pregnant Wistar rats were divided into four groups: A) Kind⁺/Seiz⁺, pregnant kindled (induced two weeks prior to pregnancy) rats that received repeated intraperitoneal (i.p.) pentylenetetrazol, PTZ injections on gestational days (GD) 14-19; B) Kind^-/Seiz⁺, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C) Kind⁺/Seiz^-, pregnant kindled rats that did not receive any PTZ injections; and D) Kind^-/Seiz^-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry.

Results

Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind⁺/Seiz⁺ (p = 0.001) and Kind^-/Seiz⁺ (p = 0.001) groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind⁺/Seiz⁺ (p = 0.007) and Kind^-/Seiz⁺ (p = 0.007) group’s newborns on both PD1 and 14.

Conclusion

Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.     

Structural effects of modified ribonucleotides and magnesium in transfer RNAs

Modified nucleotides are ubiquitous and important to tRNA structure and function. To understand their effect on tRNA conformation, we performed a series of molecular dynamics simulations on yeast tRNA^Phe and tRNA_init, Escherichia coli tRNA_init and HIV tRNA^Lys. Simulations were performed with the wild type modified nucleotides, using the recently developed CHARMM compatible force field parameter set for modified nucleotides (J. Comput. Chem. 2016, 37, 896), or with the corresponding unmodified nucleotides, and in the presence or absence of Mg²⁺. Results showed a stabilizing effect associated with the presence of the modifications and Mg²⁺ for some important positions, such as modified guanosine in position 37 and dihydrouridines in 16/17 including both structural properties and base interactions. Some other modifications were also found to make subtle contributions to the structural properties of local domains. While we were not able to investigate the effect of adenosine 37 in tRNA_init and limitations were observed in the conformation of E. coli tRNA_init, the presence of the modified nucleotides and of Mg²⁺ better maintained the structural features and base interactions of the tRNA systems than in their absence indicating the utility of incorporating the modified nucleotides in simulations of tRNA and other RNAs.     

Anticonvulsant effects of dextrorphan in rats: possible involvement in dextromethorphan-induced seizure protection

The major metabolite of the non-opioid anticonvulsant/antitussive dextromethorphan is dextrorphan. In the present study, the effects of dextrorphan were determined in an experimental model of seizure activity (maximal electroshock convulsions) (MES). Subcutaneous administration of dextrorphan produced dose-related blockade of tonic hindlimb extension (THE) and a decrease in the duration of tonic forelimb extension (TFE). The anticonvulsant effect of dextrorphan was linear and maximally efficacious. Compared to the prototypical anticonvulsant drug diphenylhydantoin, dextrorphan was 2.5 times more potent (ED50's = 30 mumol/kg and 12 mumol/kg, respectively). Pretreatment with naloxone failed to antagonize dextrorphan-induced blockade of THE. Moreover, pretreatment with dextrophan failed to significantly enhance the anticonvulsant potency of diphenylhydantoin. It is likely that the anticonvulsant effects of dextrorphan are related to its actions at the phencyclidine/N-methyl-D-aspartate receptor complex, whereas the anticonvulsant effects of dextromethorphan have been attributed to binding to a specific dextromethorphan site in the brain. Therefore, we suggest that while metabolism to dextrorphan could possibly contribute to the anticonvulsant effects of dextromethorphan, it is probably through an unrelated receptor mechanism.     

Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol

Ligands targeting central histamine H₃ receptors (H₃Rs) for epilepsy might be a promising therapeutic approach. Therefore, the previously described and structurally strongly related imidazole-based derivatives belonging to carbamate class with high H₃R in vitro affinity, in-vivo antagonist potency, and H₃R selectivity profile were investigated on their anticonvulsant activity in maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in Wistar rats. The effects of systemic injection of H₃R ligands 1–13 on MES-induced and PTZ-kindled seizures were screened and evaluated against the reference antiepileptic drug (AED) Phenytoin (PHT) and the standard histamine H₃R inverse agonist/antagonist Thioperamide (THP) to determine their potential as new antiepileptic drugs. Following administration of the H₃R ligands 1–13 (5, 10 and 15 mg/kg, ip) there was a significant dose dependent reduction in MES-induced seizure duration. The protective action observed for the pentenyl carbamate derivative 4, the most protective H₃R ligand among 1–13, was significantly higher (P <0.05) than that of standard H₃R antagonist THP, and was reversed when rats were pretreated with the selective H₃R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H₁R antagonist Pyrilamine (PYR) (10 mg/kg). In addition, subeffective dose of H₃R ligand 4 (5 mg/kg, ip) significantly potentiated the protective action in rats pretreated with PHT (5 mg/kg, ip), a dose without appreciable protective effect when given alone. In contrast, pretreatment with H₃R ligand 4 (10 mg/kg ip) failed to modify PTZ-kindled convulsion, whereas the reference drug PHT was found to fully protect PTZ-induced seizure. These results indicate that some of the investigated imidazole-based H₃R ligands 1–13 may be of future therapeutic value in epilepsy.     

Anticonvulsant effects of the wasp Polybia ignobilis venom on chemically induced seizures and action on GABA and glutamate receptors

Venoms of spiders and wasps are well recognized to present high affinity to the central nervous tissue of many mammalian species. Here we describe the effects of direct exposure of rat (Rattus norvegicus) brains to the crude and denatured venom of the Brazilian social wasp Polybia ignobilis. Lower doses of crude venom injected via intracerebroventricular (i.c.v.) inhibited the exploratory activity of animals, while higher doses provoked severe generalized tonic-clonic seizures, with hind limb extension. The status epilepticus lasted for few minutes leading the animals to respiratory depression and death. In contrast, the denatured venom was anticonvulsant against acute seizures induced by the i.c.v. injection of bicuculline, picrotoxin and kainic acid, but it was ineffective against seizures caused by systemic pentylenetetrazole. Moreover, the [3H]-glutamate binding in membranes from rat brain cortex was inhibited by the denatured venom in lower concentrations than the [3H]-GABA binding. The denatured venom contains free GABA and glutamate (34 and 802 pg/microg of venom, respectively), but they are not the major binding inhibitors. These interactions of venom components with GABA and glutamate receptors could be responsible for the anticonvulsant effects introducing the venom from P. ignobilis as a potential pharmacological source of anticonvulsant drugs.     

Characterisation of magnesium nutrition and interaction of magnesium and potassium in rice

Magnesium (Mg) is known as one of the essential nutrients for higher plants; yet, the preliminary physiological responses of field crops to its deficiency or excess, particularly to its interaction with potassium (K), remain largely unknown. In this study, we observed that Mg deficiency in rice (Oryza sativa) [less than 1.1 mg g^?1 dry weight (DW) in the shoot] resulted in significant reduction in shoot biomass, decrease in total chlorophyll concentration and net photosynthetic rate and reduction in activities of both nitrate reductase [NR; enzyme classification (EC) 1.6.6.1] and glutamine synthetase (EC 6.3.1.2) in the leaves. However, the Mg‐deficient plant contained higher starch in the leaves, and partitioned larger biomass into roots. Excess of Mg (more than 3.0 mg g^?1 DW in the shoot), together with low K supply, suppressed NR activity and decreased concentration of soluble sugar in the leaves. There were great antagonistic and moderately synergistic effects between K and Mg, but the effects of K were much more significant than those of Mg on their uptake and translocation, NR activity and net photosynthetic rate in the leaves. The optimum weight ratio of K to Mg ranged between 22 and 25 in the leaves at tillering stage. Mg deficiency was not compensated for by moderate supply of K but was aggravated by excess supply of K, suggesting specific roles of Mg in both dry matter production and partition of carbon assimilates in rice.     

Effects of magnesium sulfate on energy metabolites and glutamate in the cortex during focal cerebral ischemia and reperfusion in the gerbil monitored by a dual-probe microdialysis technique

Previous studies have demonstrated that magnesium sulfate has cytoprotective properties for treating experimental rat brain injuries. The aim of this study is to evaluate changes in energy-related metabolites and glutamate in the cortex of gerbils subjected to focal cerebral ischemia with the pretreatment of magnesium sulfate. The focal cerebral ischemia was produced by the occlusion of the right common carotid artery and the right middle cerebral artery for 60 mins. A significant decrease in infarct size was found in the magnesium sulfate treated group when compared to the controls. Two microdialysis probes were inserted bilaterally into the cortex to monitor extracellular glucose, lactate, pyruvate and glutamate during cerebral ischemia and reperfusion periods. The present study showed a dynamic decrease of glucose (10% of the baseline), pyruvate (15% of the baseline), and an increase of lactate (200% of the baseline) and glutamate (1400% of the baseline) on the ipsilateral side during ischemia in the control group. Magnesium sulfate significantly preserved glucose (up to 50% of the baseline) and pyruvate (70% of the baseline) levels in the ipsilateral side during ischemia. There was significant attenuation in the elevation of glutamate and lactate (500% and 150% of the baseline, respectively) when treatments of magnesium sulfate were administered. No significant influence on these neurochemicals in the contralateral side was observed in either group. These results suggest that both the preservation of cellular energy metabolism, and the attenuation of glutamate release during cerebral ischemia and after restoration of reperfusion may contribute to the neuroprotective effects of magnesium sulfate.     

Analysis of connexin expression during seizures induced by 4-aminopyridine in the rat hippocampus

Background

In epilepsy, seizures are generated by abnormal synchronous activity in neurons. In the rat hippocampus (HIP), epileptiform activity has been found to be associated with gap junctions (GJs). GJs are formed by the combination of two hemichannels, each composed of six connexins. At low doses, the convulsive drug 4-aminopyridine (4-AP) produces epileptiform activity without affecting glutamate levels; therefore, GJs could participate in its effect. Based on this argument, in this study, the expression of Cx 32, Cx 36 and Cx 43 protein and mRNA in the HIP of rats treated with 4-AP was evaluated. The evaluation of connexins was carried out by chemifluorescent immunoassay, semiquantitative RT-PCR and immunofluorescence to detect the amount and distribution of connexins and of cellular markers in the HIP and dentate gyrus (DG) of animals treated with NaCl and 4-AP in the right entorhinal cortex. In these animals, convulsive behavior and EEG signals were analyzed.

Results

The animals treated with 4-AP showed convulsive behavior and epileptiform activity 60 min after the administration. A significant increase in the protein expression of Cx 32, Cx 36 and Cx 43 was found in the HIP contralateral and ipsilateral to the site of 4-AP administration. A trend toward an increase in the mRNA of Cx 32 and Cx 43 was also found. An increase in the cellular density of Cx 32 and Cx 43 was found in the right HIP and DG, and an increase in the cellular density of oligodendrocytes in the DG and a decrease in the number of cells marked with NeuN were observed in the left HIP.

Conclusions

Cx 32 and Cx 43 associated with oligodendrocytes and astrocytes had an important role in the first stages of seizures induced by 4-AP, whereas Cx36 localized to neurons could be associated with later stages. Additionally, these results contribute to our understanding of the role of connexins in acute seizures and allow us to direct our efforts to other new anticonvulsant strategies for seizure treatment.     

Effect of magnesium deficiency on the metabolism of glycosamino-glycans in rats

Magnesium deficiency in rats has significant effect on the concentration of different glycosaminoglycans in the tissues, the nature of the change being different in different tissues. Total glycosaminoglycans, chondroitin-4-sulphate + chondroitin-6-sulphate and dermatan sulphate increased in the aorta while hyaluronic acid, heparan sulphate and heparin decreased. In the liver, total glycosaminoglycans, hyaluronic acid, chondroitin-4-sulphate + 6-sulphate and heparin decreased while total glycosamino-glycans and all the glycosaminoglycan fractions increased in the heart. In the kidney, total glycosaminoglycans showed no significant alteration, hyaluronic acid and heparin decreased while chondroitin-4-sulphate + 6-sulphate increased. Activity of biosynthetic enzymesviz. glucosamine-o-phosphate isomerase and UDPG-dehydrogenase showed decrease in the liver. The concentration of 3’-phosphoadenosine 5’-phosphosulphate, activity of sulphate activating system and sulphotransferase were also similarly altered in the liver in magnesium deficiency.     

Osmotic and specific effects of magnesium sulphate on the mineral content ofZea mays

Summary The effects which the osmotic pressures 2.0, 3.5 and 5.0 atm., obtained by the addition of either magnesium sulphate or PEG-4000 to the standard nutrient solution, have on the development and mineral content ofZea mays var. INIA 8302 are assessed. The osmotic effect causes a greater absorption of cations, potassium being the element most readily absorbed. The specific effect of magnesium sulphate causes a decrease in the total of anions and in the water content of the plant and partly offsets the decrease which the osmotic effect produces in the fresh weight.     

Differential Changes in the Content of Amino Acid Neurotransmitters in Discrete Regions of the Rat Brain Prior to the Onset and During the Course of Homocysteine-Induced Seizures

Changes in amino acid concentrations were investigated in selected regions of rat brain prior to the onset and during the course of epileptiform seizures induced by L-homocysteine. The concentration of gamma-aminobutyric acid (GABA) decreased preictally in substantia nigra (-18%), caudate putamen (-26%), and inferior colliculus (-46%). After seizure onset, the GABA content was further reduced in substantia nigra (-31%) and additionally in hippocampus (-18%). Preictal taurine levels were elevated in globus pallidus (+26%) and caudate putamen (+13%) but returned to normal after seizure onset. However, in hippocampus, taurine decreased both preictally (-22%) and after seizure onset (-56%). Glycine was reduced preictally only in globus pallidus (-13%). After seizure onset the direction of its concentration change varied in the brain regions studied. Glutamate levels decreased preictally in hippocampus (-10%) and hypothalamus (-46%) but increased in globus pallidus (+14%). Normal levels were detectable after seizure onset in hypothalamus and globus pallidus but a further reduction in hippocampus (-59%) and significant reductions in substantia nigra (-15%) and caudate putamen (-17%) were detected. Aspartate was elevated in hippocampus, both preictally (+49%) and after seizure onset (+21%) while at the same phases in globus pallidus a consistent reduction (-30%) was observed. The glutamine content increased preictally in globus pallidus (+41%) and hypothalamus (+36%), and in all brain areas during the ictal phase of seizure, the hippocampus exhibiting a dramatic increase (approximately 300%). The contents of serine and alanine were altered in most regions studied only after seizure onset, with the exception of the hippocampus, where a decrease (-41%) of serine was observed preictally.     

Induction of c-fos mRNA Expression by Afterdischarge in the Hippocampus of Naive and Kindled Rats

Periodic induction of focal electrical seizure [afterdischarge (AD)] is an absolute prerequisite for the development of kindling, an animal model of complex partial epilepsy. Once established, it is a permanent condition. The mechanism(s) that translate ADs, which last tens of seconds, into life-long alterations in the CNS is unclear. Cellular immediate-early genes have been implicated in the conversion of short-term stimuli to long-term alterations in cellular phenotypes by regulating target gene expression. We have investigated the contribution of one such early gene, c-fos, to this process. The relationship between ADs and expression of c-fos gene in the rat hippocampus, a key structure in kindling development, was studied by analysis of mRNA levels. The low constitutive expression of c-fos mRNA in the hippocampus was not altered by kindling. There was an "all-or-none" relationship between induction of c-fos and the duration of AD. The threshold for induction was approximately 30 s of AD. Above-threshold ADs induced c-fos in both naive and kindled animals to the same extent and with identical temporal profiles. Although the expression of c-fos is unchanged with kindling, c-fos may nonetheless contribute to many long-term changes of kindling, both adaptive and epileptogenic.     

Mitigation of adverse effects of heat stress on Vicia faba by exogenous application of magnesium

The effects of magnesium (Mg) supplementation on the growth performance, oxidative damage, DNA damage, and photosynthetic pigment synthesis, as well as on the activity level of carbonic anhydrase (CA), ribulose-1,5-bisphosphate carboxylase (Rubisco), and antioxidant enzymes were studied in Vicia faba L. plants exposed to heat stress (HS) and non-heat-stress (non-HS) conditions. Seeds were grown in pots containing a 1:1 mixture of sand and peat, with Mg treatments. The treatments consisted of (i) 0 Mg and non-HS (ambient temperature; control); (ii) 50 mM Mg; (iii) HS (38 °C); and (iv) 50 mM Mg and HS (38 °C). HS was imposed by placing potted plants in an incubator at 38 °C for 48 h. Growth attributes, total chlorophyll (Total Chl), and CA, and Rubisco activity decreased in plants subjected to HS, whereas accumulation of organic solutes [proline (Pro) and glycine betaine (GB)]; superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activity; DNA damage; electrolyte leakage (EL); and malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) content all increased. Application of Mg, however, significantly enhanced further proline (Pro), glycinebetaine (GB), SOD, POD, and CAT activity, and decreased DNA damage, EL, and MDA and H₂O₂ concentrations. These results suggest that adequate supply of Mg is not only essential for plant growth and development, but also improves plant tolerance to HS by suppressing cellular damage induced by reactive oxygen species through the enhancement of the accumulation of Pro and GB, and the actions of antioxidant enzymes.