Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of 2-amino-3-phosphonopropionate (AP-3), a metabotropic glutamate receptor antagonist on behavioral and histological changes following global ischaemia was investigated on the Mongolian gerbil. Ischaemia was induced by bilateral carotid occlusion for 5 min. AP-3 was administered i.p. (25 or 250 mg/kg) 30 min before and 24 h after surgery. Significant neuroprotection was observed 96 h after surgery to cells in the CA1 region of the hippocampus in drug treated animals. AP-3 (250 mg/kg) significantly attenuated the increase in locomotor activity measured 72 h after surgery. These results suggest that metabotropic glutamate receptors play a role in the neurodegeneration seen following ischaemia.
...
PMID:The effect of 2-amino-3-phosphonopropionic acid (AP-3) in the gerbil model of cerebral ischaemia. 749 86

Metabotropic glutamate receptors mediate their intracellular response by coupling to G proteins and may be divided into three subfamilies: mGluR1 and mGluR5, which stimulate phosphatidylinositol hydrolysis; mGluR2 and mGluR3, which are negatively coupled to cyclic AMP formation; and mGluR4 and mGluR6, which also inhibit forskolin-stimulated cyclic AMP formation. The mGluR4 subtypes may represent L-2-amino-4-phosphonobutyrate-sensitive presynaptic autoreceptors, and two alternatively spliced variants of the mGluR4 coding for two receptors with different C termini have been identified. Using in situ hybridization, we measured the levels of mGluR1-mGluR5 mRNA in regions of the rat brain 24 h after transient global ischemia, a time point when no neuronal damage can yet be observed morphologically. In the hippocampus, the mRNA levels for mGluR1, mGluR2, and mGluR5 were decreased, mGluR3 mRNA levels were unchanged, and the mGluR4 mRNA levels were strongly increased. The strongest increase appeared to be in the mRNA encoding mGluR4b. The mGluR4 mRNA was also increased in the parietal cortex, whereas the ventral posteromedial thalamic nucleus showed a small decrease in its mRNA content. These results suggest that vulnerable neurons react to an increased extracellular glutamate concentration by differential regulation of the mRNA for pre- and postsynaptically located metabotropic glutamate receptors.
...
PMID:Changes in metabotropic glutamate receptor mRNA levels following global ischemia: increase of a putative presynaptic subtype (mGluR4) in highly vulnerable rat brain areas. 803 86

Effects of intrauterine hypoxia-ischemia (HI) on receptor-stimulated phosphoinositide (PPI) hydrolysis were studied in rat cerebellar granule cell cultures prepared from an in utero HI model. On gestation day 17, HI conditions were achieved by complete clamping of the uterine vasculature for 30 min followed by removal of the clamps to permit reperfusion. Sham operation (SH, surgery without vasculature ligation) was performed as the control. Intrauterine HI did not affect the basal level of PPI hydrolysis (in the absence of stimulants) in cells prepared from either the SH or the HI group. PPI hydrolysis stimulated by quisqualate (QA) or trans-(1S,3R)-1-amino-1,3-cyclo-pentanedicarboxylic acid (trans-ACPD) was significantly reduced in cells prepared from the HI group, whereas intrauterine HI did not affect the PPI hydrolysis induced by ionotropic glutamate receptor agonists or by norepinephrine or serotonin. At a dose range of 100-300 microM, QA-stimulated PPI hydrolysis in cells prepared from the SH group increased by 3-to 4.5-fold, while this increase was only 2- to 2.5-fold in cells prepared from the HI group. Presence of L-NG-monomethyl-arginine (L-NMMA), a nitric oxide (NO) synthase inhibitor, did not increase QA-stimulated PPI hydrolysis in cells prepared from either the SH or the HI group, indicating that stimulation of NO formation is unlikely involved in the suppressive effects of intrauterine HI on QA-induced PPI hydrolysis. The QA-stimulated PPI hydrolysis in cells prepared from the HI group, but not from the SH group, was further inhibited by L-(+)-2-amino-3-phosphono-propionic acid (L-AP3). The overall results suggest that intrauterine HI has long-lasting suppressive effects on metabotropic glutamate receptor agonist-stimulated PPI hydrolysis and these effects might be associated with alterations in expression of metabotropic glutamate receptor subtypes.
...
PMID:Intrauterine hypoxia-ischemia reduces phosphoinositide hydrolysis stimulated by metabotropic glutamate receptor agonists in cultured rat cerebellar granule cells. 880 99

Excitotoxicity has been proposed to contribute to neuronal loss in a broad spectrum of neurodegenerative conditions such as ischemia, hypoglycaemic coma or cerebral trauma. Excitotoxic neuronal injury appears to be mediated mainly by the over-activation of glutamate receptors, especially N-methyl-D-aspartate receptors, with subsequent excessive Ca2+ influx. Concurrent with the activation of glutamate-gated ion channels, metabotropic glutamate receptors (mGluR), which are G-protein coupled receptors, are also expected to be activated. Excessive stimulation of phospholipase C-coupled mGluR, mGluR1 and mGluRS, has been suggested to have neurotoxic consequences. However, the contribution of mGluR activation on excitotoxicity is still unclear and controversial. Here we report that, following ischemic and excitotoxic brain injuries, inactivation of mGluR1 does not prevent excitotoxic neuronal damage. Given the evidence that agonists at this group of mGluR promoted neuronal death in cerebrocortical cultures after oxygen-glucose deprivation or after N-methyl-D-aspartate exposure, our findings suggest that mGluR-mediated excitotoxicity is unlikely associated with mGluR1 but rather with other PLC-coupled mGluR.
...
PMID:Evidence against a permissive role of the metabotropic glutamate receptor 1 in acute excitotoxicity. 917 62

1. Glutamate is the neurotransmitter released by bipolar cells at their synapses with amacrine cells. The amacrine cells express ionotropic (NMDA, AMPA and kainate) and metabotropic (mGluR1, mGluR2, mGluR4 and mGluR7) glutamate receptors and may take up glutamate from the synaptic cleft. 2. Activation of the ionotropic glutamate receptors increases the intracellular free calcium concentration ([Ca2+]i), owing to Ca2+ entry through the receptor-associated channels as well as through voltage-gated Ca2+ channels. The [Ca2+]i response to glutamate may be amplified by Ca2+-induced Ca2+ release from intracellular sources. 3. Activation of NMDA and non-NMDA glutamate receptors stimulates the release of GABA and acetylcholine from amacrine cells. GABA is released by a Ca2+-dependent mechanism and by reversal of the neurotransmitter transporter. 4. Excessive activation of glutamate receptors during ischemia leads to amacrine cell death. An increase in [Ca2+]i due to Ca2+ influx through NMDA and AMPA/kainate receptor channels is related to cell death in studies in vitro. In other studies, it was shown that nitric oxide may also take part in the process of cell damage during ischemia.
...
PMID:Glutamate in life and death of retinal amacrine cells. 951 76

This study investigated whether the metabotropic glutamate receptor ligand (S)-4C3HPG can reduce brain damage after focal ischemia in rats. Application of 1 micromol of (S)-4C3HPG (intracerebroventricularly) 5 min after occlusion of the middle cerebral artery significantly reduced the infarct size by 72.3% of the saline control.
...
PMID:(S)-4C3HPG reduces infarct size after focal cerebral ischemia. 988 89

The expression of group I metabotropic glutamate receptors (mGluR1 and mGluR5) and inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) mRNA was studied by in situ hybridization in the developing rat hippocampus after in utero hypoxia-ischemia. In utero hypoxia-ischemia was induced by clamping the uterine blood vessels of near-term fetuses for 10 min. Fetuses were delivered surgically, resuscitated and raised by foster mothers until postnatal day 7 and 14. Results indicated a temporal delay in the expression of mGluR1 mRNA in the dentate gyrus of the ischemic animals. The mGluR1 mRNA level was significantly lower in the ischemic animals at postnatal day 7, but reached a similar level as that of controls at postnatal day 14. In utero hypoxia-ischemia did not change the temporal-spatial expression pattern of either mGluR5 or IP3R1 mRNA in the hippocampus. Between postnatal day 7 and 14, mGluR5 mRNA showed a high and relatively constant expression, whereas IP3R1 mRNA levels were increased in all regions examined. The differences in the expressions of group I mGluRs indicate that these receptors may have different functions during hippocampal development and may play different roles in excitotoxicity.
...
PMID:Changes in mRNA levels for group I metabotropic glutamate receptors following in utero hypoxia-ischemia. 997 57

Excessive release of glutamate during ischemia leads to sustained neuronal damage. In this study we investigated the influence of metabotropic glutamate receptor (mGluR) activation on neuronal recovery from a hypoxic/hypoglycemic event in hippocampal slices from rats. The slices were transiently exposed to an oxygen- and glucose-free environment in an interface chamber and the synaptically evoked population spike in the CA1 region was taken as a measure of neuronal viability. Under control conditions the population spike amplitude recovered to 41.4% of baseline value within 1 h after hypoxia/hypoglycemia. The specific mGluR group I agonist 3,5-dihydroxyphenylglycine (DHPG, 10 microM) increased the recovery rate to 88.3% of baseline value when applied from 20 min before until 10 min after the event. Similar recovery rates were obtained when DHPG was present only 10 or 20 min before hypoxia/hypoglycemia (89.3% and 79.3% of baseline value, respectively). However, when applied later, DHPG had no protective effect. Co-application of the protein kinase C (PKC) inhibitors staurosporine (100 nM) or chelerythrine (30 microM) prevented the protective effect of DHPG. Our data suggest that group I mGluR agonists are only protective when present prior to the onset of the hypoxic/hypoglycemic event and that the activation of PKC is a critical step of the protective mechanism.
...
PMID:Protective effect of group I metabotropic glutamate receptor activation against hypoxic/hypoglycemic injury in rat hippocampal slices: timing and involvement of protein kinase C. 1021 61

Changes in interneuron distribution and excitatory connectivity have been investigated in animals which had survived 12-14 months after complete forebrain ischemia, induced by four-vessel occlusion. Anterograde tracing with Phaseolus vulgaris leucoagglutinin revealed massive Schaffer collateral input even to those regions of the CA1 subfield where hardly any surviving pyramidal cells were found. Boutons of these Schaffer collaterals formed conventional synaptic contacts on dendritic spines and shafts, many of which likely belong to interneurons. Mossy fibres survived the ischemic challenge, however, large mossy terminals showed altered morphology, namely, the number of filopodiae on these terminals decreased significantly. The entorhinal input to the hippocampus did not show any morphological alterations. The distribution of interneurons was investigated by neurochemical markers known to label functionally distinct GABAergic cell populations. In the hilus, spiny interneurons showed a profound decrease in number. This phenomenon was not as obvious in CA3, but the spiny metabotropic glutamate receptor 1alpha-positive non-pyramidal cells, some of which contain calretinin or substance P receptor, disappeared from stratum lucidum of this area. In the CA1 region, somatostatin immunoreactivity disappeared from stratum oriens/lacunosum-moleculare-associated cells, while in metabotropic glutamate receptor 1alpha-stained sections these cells seemed unaffected in number. Other interneurons did not show an obvious decrease in number. In stratum radiatum of the CA1 subfield, some interneuron types had altered morphology: the substance P receptor-positive dendrites lost their characteristic radial orientation, and the metabotropic glutamate receptor 1alpha-expressing cells became extremely spiny. The loss of inhibitory interneurons at the first two stages of the trisynaptic loop coupled with a well-preserved excitatory connectivity among the subfields suggests that hyperexcitability in the surviving dentate gyrus and CA3 may persist even a year after the ischemic impact. The dorsal CA1 region is lost; nevertheless hyperactivity, if it occurs, may have a route to leave the hippocampus via the longitudinally extensive axon collaterals of CA3 pyramidal cells, which may activate the subiculum and entorhinal cortex with a relay in the surviving ventral hippocampal CA1 region.
...
PMID:Changes in excitatory and inhibitory circuits of the rat hippocampus 12-14 months after complete forebrain ischemia. 1039 28

Glutamate is the major excitatory neurotransmitter in the brain and plays a unique role in a variety of central nervous system (CNS) functions. The discovery of the metabotropic receptors (mGluRs), a family of G-protein coupled receptors than can be activated by glutamate, has led to an impressive number of studies in recent years aimed at understanding their biochemical, physiological and pharmacological characteristics. The eight mGluRs now known are divided into three groups according to their sequence homology, signal transduction mechanisms, and agonist selectivity. Group I mGluRs include mGluR1 and mGluR5, which are linked to the activation of phospholipase C; Groups II and III include all others and are negatively coupled to adenylyl cyclases. The availability in recent years of agents selective for Group I mGluRs has made possible the study of the physiological roles of these receptors in the CNS. In addition to mediating glutamatergic neurotransmission, Group I mGluRs can modulate other neurotransmitter receptors, including GABA and the ionotropic glutamate receptors. Group I mGluRs are involved in many CNS functions and may participate in a variety of disorders such as pain, epilepsy, ischemia, and chronic neurodegenerative diseases. This class of receptor may provide important pharmacological therapeutic targets and elucidating its functions will be relevant to develop new treatments for neurological and psychiatric disorders in which glutamatergic neurotransmission is abnormally regulated. In this review anatomical, physiological and pharmacological results are presented with a special emphasis on the role of Group I mGluRs in functional and pathological processes.
...
PMID:Group I metabotropic glutamate receptors: implications for brain diseases. 1041 61


1 2 3 4 5 Next >>

---