Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous work in our laboratory demonstrated that ischemic-hypoxic brain injury in postnatal day 7 rats causes a substantial increase in phosphoinositide (PPI) turnover stimulated by the glutamate analogue quisqualic acid (QUIS) in the hippocampus and striatum. To examine this phenomenon in more detail, we performed similar experiments after producing injury by unilateral intracerebral injections of the glutamate analogue N-methyl-D-aspartate (NMDA). The 7-day-old rodent brain is hypersensitive to NMDA neurotoxicity and NMDA injection causes histopathology that closely resembles that produced by ischemia-hypoxia. NMDA, 17 nmol in 0.5 microliter, was injected into the right posterior striatum of 7-day-old rat pups and they were killed 3 days later. Hippocampal or striatal tissue slices were prepared from ipsilateral and contralateral hemispheres from vehicle-injected control and from noninjected control rat pups. Slices were then incubated with myo-[3H]inositol plus glutamate agonists or antagonists in the presence of lithium ions and [3H]inositol monophosphate ([3H]IP1) accumulation was measured. The glutamate agonists, QUIS, L-glutamic acid, and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, stimulated greater [3H]IP1 release in tissue ipsilateral to the NMDA injection compared with that in the contralateral side and in control pups. The glutamate antagonists, D,L-2-amino-7-phosphonoheptanoic acid, 3-[(+)-2-carboxypiperazin-4-yl]-propyl-1-phosphoric acid, kynurenic acid, and 6,7-dinitroquinoxaline-2,3-dione did not inhibit QUIS-stimulated [3H]IP1 release. The enhanced PPI turnover in the lesioned tissue was specific to glutamate receptors because carbachol (CARB) failed to elicit preferential enhanced stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:N-methyl-D-aspartate-mediated injury enhances quisqualic acid-stimulated phosphoinositide turnover in perinatal rats. 132 76

The protective effect of the anticonvulsant MK-801 and the antitussive dextromethorphan, which are both N-methyl-D-aspartate receptor antagonists, and kynurenic acid, a broad-spectrum excitotoxin antagonist, was tested in cultured rat retinal cells in an hypoxic environment. The protective effect of these antagonists also was tested in cultured retinal cells and in intact adult rat retinas exposed to the exogenous excitotoxins L-glutamic acid and N-methyl-D-aspartic acid. MK-801 and kynurenic acid protected retinal neurons from hypoxic damage and from the toxicity of exogenous L-glutamic acid and N-methyl-D-aspartic acid. Dextromethorphan, a less potent antagonist, did not protect the retinal neurons from hypoxic damage or the toxicity of exogenous L-glutamic acid, but did attenuate N-methyl-D-aspartate toxicity. These results provide evidence that the synaptic release of excitatory transmitters, most likely glutamate and aspartate, mediate the death of hypoxic retinal neurons. Compounds related to MK-801 may have possible therapeutic applications in the management of retinal ischemia.
 ...
PMID:MK-801 protects retinal neurons from hypoxia and the toxicity of glutamate and aspartate. 135 58

Changes in content of selected neuroactive amino acids [glutamic acid, aspartic acid, glycine, gamma-aminobutyric acid (GABA) and taurine] and acetylcholine (ACh) in the rat hippocampus following transient forebrain ischemia were investigated using male Wistar rats. Rats were allowed to survive for 1 or 5 days following 10 or 20 min of 4-vessel occlusion, and killed by a focused microwave irradiation. A significant reduction in all neuroactive amino acids examined except GABA was noted in the hippocampus on the fifth day. One day after the 4-vessel occlusion for 10 min, no significant effect on the content of neuroactive amino acids in all brain areas was observed. gamma-Aminobutyric acid content in the hippocampus was only significantly reduced on the fifth day after the occlusion for 20 min. Similarly, a significant decrease in ACh content in the hippocampus was observed on the fifth day after the occlusion for 20 min. Considering the data that a significant loss of neuronal cells in the hippocampus (delayed neuronal death) was detected only 5 days after the 4-vessel occlusion, it can be said that the alterations in the hippocampus of neuroactive amino acids such as glutamic acid, aspartic acid, glycine and taurine are more sensitive than those in GABA and ACh against cerebral ischemia. A possible correlation of these changes of neuroactive amino acids in the occurrence of delayed neuronal death in the hippocampus is also suggested.
 ...
PMID:Changes in content of neuroactive amino acids and acetylcholine in the rat hippocampus following transient forebrain ischemia. 136 66

The protective effect of vinconate, a vinca alkaloid derivative, on ischemia-induced neuronal damage was investigated using a model of rat forebrain ischemia caused by occlusion of four vessels. Hippocampal cell loss was observed histologically and neurochemically 5 days after 10 min of ischemia. Treatment with vinconate (50 and 200 mg/kg i.p.) before cerebral ischemia significantly suppressed neuronal cell loss in the hippocampal CA1 region and the decrease in the content of neuroactive amino acids in the hippocampus. The release of neuroactive amino acids in the hippocampus was significantly increased by cerebral ischemia. Pretreatment with vinconate (50 and 200 mg/kg i.p.) significantly attenuated the increased release of glutamic acid and aspartic acid, but not the release of gamma-aminobutyric acid (GABA), taurine and glycine. This suppressive effect of vinconate was antagonized by scopolamine (10(-5) M). The addition of vinconate (10(-11)-10(-4) M) had no effect on the binding of [3H]MK-801. These results indicate that pretreatment with vinconate attenuates the ischemia-induced release of excitatory amino acids into the extracellular space of the hippocampus via the stimulation of presynaptic muscarinic acetylcholine receptors. The present results also suggest that this suppressive effect of vinconate on the release of excitatory amino acids (glutamic acid and aspartic acid) may play a crucial role in the protective action of this agent against ischemia-induced neuronal damage in the hippocampus.
 ...
PMID:Protective effect of vinconate on ischemia-induced neuronal damage in the rat hippocampus. 146 4

A massive striatal dopamine release (241-fold increase) was observed in a previous study during acute cerebral ischemia in rats. In this study, extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and lactic acid were simultaneously determined using in vivo brain dialysis in the striatum of spontaneously hypertensive rats during cerebral ischemia and after recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM) of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia. Although ischemia-induced release of GLU and GABA was demonstrated in this study, the degree of increase was smaller than that of dopamine. These findings may be relevant to the pathophysiology of cerebral ischemia in the striatum.
 ...
PMID:Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia in spontaneously hypertensive rats. 197 32

The region surrounding a focal cerebral infarct shows selective rather than generalized neuronal damage. The "ischemic penumbra" has been defined electrophysiologically as that region which shows a loss of electrical activity while retaining some metabolic viability (Astrup et al., Stroke, 1981:6:723-5). How factors that contribute to ischemic damage may cause such selective damage to subpopulations of neurones will be discussed. Particular attention will be directed to the cortical pyramidal cells, thought to be a major component of cerebral electrical activity. The N-methyl-D-aspartate (NMDA) class of glutamic acid receptors appears to have a role in certain aspects of ischemic damage, mediated through excitotoxins and calcium ions. The regulation of this receptor complex appears to be unaffected by ischemia, and thus it may provide a target for possible therapeutic interventions. Selective neuronal loss tends to be associated with neurotransmitter imbalance; therefore, treatments designed to correct this imbalance by affecting the activity of those cells less sensitive to ischemia may provide an alternative approach to establish normal cerebral function.
 ...
PMID:Can we reverse ischemic penumbra? Some mechanisms in the pathophysiology of energy-compromised brain tissue. 198 5

L-Glutamate and related excitatory amino acids (EAA) are firmly established as major excitatory synaptic transmitter substances in the vertebrate central nervous system. Questions which have been addressed include: How many receptors are there for the EAAs?; What ion channels and/or 'second-messenger' systems are regulated by these receptors?; What are the roles of EAAs in higher neural functions?; Are they involved in neurological disorders? EAA receptors appear not only to mediate normal synaptic transmission along excitatory pathways but also to participate in the modification of synaptic connections during development. However, overaction of receptors can also mediate neuronal degeneration and even cell death. NMDA receptor antagonists markedly attenuate neuronal necrosis. Therefore, it appears that ischemia- and hypoglycemia-associated brain damage results not from a lack of energy substrates but rather via the mediation of NMDA receptors and 'excitotoxic' mechanisms. The action of ketamine anesthesia is closely associated with a block of the NMDA receptor. Ketamine binds to a site within the lumen of the NMDA-activated channel and can become trapped there when the channel closes. Current evidence indicated that NMDA receptor antagonists will be of value for the treatment of delayed neuronal death. NMDA receptor will lead to understanding the mechanisms underlying learning and memory, the control of neuronal excitability and neuronal death.
 ...
PMID:[Synaptic mechanisms of excitatory amino acids and NMDA receptor mediated brain excitability]. 217 10

The concentration of 18 alpha-amino acids (AAs) in plasma and renal cortical cell water were measured 3 or 24 hr after 1 hr of unilateral renal artery clamping or 24 or 48 hr after 15 mg/kg body weight HgCl2 injection sc as a test of epithelial integrity. Cellular glycine (Gly), hydroxyproline (Hpr), ornithine (Orn), phenylalanine (Phe), serine (Ser), and tryptophan (Trp) concentrations were depressed 24 hr after HgCl2 (p less than 0.05), but the remaining 12 AAs were not distinguishable from control despite the presence of severe renal failure. ARginine (Arg), glutamic acid (Glu), and valine (Val) also were decreased (P less than 0.05) 24 hr later, but concentrations of half of all measured AAs were still normal. Cellular alanine (Ala), Arg, Glu, Gly, Phe, and Ser concentrations were decreased 3 hr after ischemia, p less than 0.05, but 12 AAs were unchanged and only Arg, Phe, Ser, and threonine (Thr) were reduced 24 hr after ischemia was reversed. Concentrations of even the most affected AAs remained notably higher than in plasma in both forms of acute renal failure (ARF). Total loss of AAs from a small proportion of tubular cells would be hidden by essentially normal concentrations in the rest, and such losses may well have occurred. Unless cellular AAs in ARF are almost completely bound, however, the well-maintained cell:plasma AA concentration ratios indicate that cellular energetics were adequate for AA uptake and that epithelial permeability to AAs in the vast majority of cells was not greatly disturbed. Such findings suggest that most of the epithelium, although seriously damaged, had remained viable.
 ...
PMID:Renal epithelial amino acid concentrations in mercury-induced and postischemic acute renal failure. 221 14

We have previously reported that chronic administration of valproate in developing mice decreased brain aspartic and glutamic acid levels and increased the brain taurine content. The direction of the valproate-induced changes in the cerebral levels of these neurotransmitter amino acids - excitatory in the case of aspartate and glutamate, inhibitory in the case of taurine - appeared relevant to the mechanism of its anticonvulsant action. Since the neuropathology of hypoxia-ischemia also appears to be mediated by release of glutamate/aspartate at the synapse, the valproate-induced reduction of the levels of these neuroexcitatory/neurotoxic amino acids suggested that valproate might increase the tolerance of young mice to anoxia. A doubling of the length of survival of the intact animal in an atmosphere of pure nitrogen gas and a three-fold increase in the duration of respiratory activity (gasping) of the isolated head after chronic administration of valproate support the speculation.
 ...
PMID:Valproate doubles the anoxic survival time of normal developing mice: possible relevance to valproate-induced decreases in cerebral levels of glutamate and aspartate, and increases in taurine. 250 8

The neuroprotective effects of riluzole, a novel antiglutamate, has been demonstrated in a model of ischemia induced in female Mongolian gerbils by transient bilateral carotid occlusion. Riluzole was administered at a dose of 4 mg/kg, i.p., just before, 4 hr after, and for the 14 d following the transient bilateral carotid occlusion (10 min). The functional sequelae of ischemic damage were assessed using a memory test (passive avoidance) and the extent of neuronal damage by histological examination and quantitative autoradiography of muscarinic cholinergic receptors in the hippocampus. The performance of the ischemic gerbils in the memory test was about half that of control animals. This memory deficit was completely reversed in animals treated with riluzole. This protective effect of riluzole was confirmed by histological and autoradiographic studies. The neuronal degeneration of CA1 pyramidal cells in the hippocampus observed in the ischemic group was not seen in the riluzole-treated animals, which resembled the control group. This neuronal degeneration in the CA1 area was confirmed by a quantitative measurement of muscarinic receptors: The binding was decreased by a third in the lacunosum moleculare, the stratum oriens, and the stratum radiatum. By contrast in riluzole-treated gerbils, this decrease was reversed by 50%. Finally, a clear-cut correlation was found between the deficit in the memory test and the decrease in muscarinic receptor binding in the CA1 fields. These results are compatible with the idea that glutamic acid may be involved in the neuronal degeneration of the hippocampus following ischemia, and could be foreseeable.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils. 258 51


1 2 3 4 5 6 7 8 9 Next >>