Spinal cord ischemia-induced elevation of amino acids: Extracellular measurement with microdialysis

Rk, Simpson; Cs, Robertson; Jc, Goodman

doi:10.1007/bf00973755

Cited by 92 publications

(28 citation statements)

References 30 publications

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“…Several studies have shown a rapid elevation of the extracellular concentration of glutamate and aspartate in traumatic 38,39 and ischemic 40 spinal cord lesions consistent with the hypothesis that these lesions are associated with a release of these excitatory amino acids at the lesion site. In the weight-drop model, Demediuk et al (1989) observed increased extracellular glutamate and aspartate as early as 5 min after SCI and found that the release of these amino acids was delayed, time-dependent and related to the severity of injury.…”

Section: Discussionsupporting

confidence: 58%

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

Tator

1999

Spinal Cord

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Objectives: To determine whether MK801, an NMDA receptor antagonist, blocks glutamate excitotoxicity directly or via other mechanisms such as improving blood supply at the injury site in a rat model of spinal cord injury (SCI). In the present study, the e ects of pre-and posttreatment with MK801 on axonal function, spinal cord blood¯ow (SCBF) and cord water content were studied after acute SCI in rats. Methods: Somatosensory evoked potentials (SSEPs) and cerebellar evoked potentials (CEPs) were used to quantify electrophysiological function, and the hydrogen clearance technique and wet-dry weight measurements were used to measure SCBF and cord water content, respectively. Twenty rats received a 21 g clip compression injury of the cord at T1, and were then randomly and blindly allocated to either MK801 or saline groups. Each rat received an intravenous infusion of drug or saline four times during the experiment (16 min/infusion) with the ®rst infusion (MK801 3 mg/kg) beginning 8 min pre-injury, and the other infusions (MK801 1.5 mg/kg) at 1 h intervals after injury. Control experiments on uninjured rats were performed in 10 rats using the same procedure as above except the clip compression injury of the cord was omitted. Results: In the MK801 groups with or without SCI, the amplitude of the evoked potential peaks, especially the SSEPs, was signi®cantly lower than in the saline group. There were no di erences in SCBF or cord water content between the MK801 and saline groups. Conclusion: Pre-and posttreatment with MK801 inhibits evoked potentials, but does not improve SCBF or cord edema after acute compression SCI in rats. For the ®rst time it has been shown that MK801 produced a blockade of glutamate excitatory transmission in a erent pathways after SCI. Further work is required to determine whether this inhibition is reversible and related to neuroprotection and functional recovery after SCI.

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Section: Discussionsupporting

confidence: 58%

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

Tator

1999

Spinal Cord

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“…This evidence includes: 1. The significant increase in EAA levels during the first ten minutes after ischaemia [93,94]; 2. The distribution of ischaemic damage coincides with the distribution of EAA receptors in several brain areas [95]; 3.…”

Section: Glutamate Neurotoxicitymentioning

confidence: 99%

Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA

Robin

Kalloniatis

1992

Doc Ophthalmol

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Conditions causing a reduction of oxygen availability (anoxia), such as stroke or diabetes, result in drastic changes in ion movements, levels of neurotransmitters and metabolites and subsequent neural death. Currently, there is no clinically available treatment for anoxia induced neural cell death resulting in drastic and permanent central nervous system dysfunction. However, there have been some exciting developments in experimentally induced anoxic conditions where several classes of drugs appear to significantly reduce neural cell death. This report aims to provide the foundations for understanding both the basic mechanisms involved in retinal ischaemic damage and experimental treatments used to prevent such damage. We discuss the normal release, actions and uptake of the fast retinal neurotransmitters, glutamate and GABA, in the vertebrate retina. Immunocytochemistry is used to demonstrate that both glutamate and GABA are found in the macaque retina. Following this is a discussion on how ischaemia may enhance neurotransmitter release or disrupt its uptake, thus causing an increase in extracellular concentration of these neurotransmitters and subsequent neuronal damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because excess glutamate is the likely cause of retinal ischaemic damage. Finally, the mechanisms behind four possible modes of treatment of neurotransmitter toxicity and their advantages and disadvantages are discussed. Hopefully, further research in this area will lead to the development of a rational therapy for retinal, as well as cerebral ischaemia.

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“…GSH was measured by the method of Tietze (30) by using a COBAS-BIO centrifugal analyzer (Roche Diagnostics). Plasma amino acid levels were measured as previously described (31 coat color. These chimeras were mated, and genotype analysis of agouti offspring with the 3' DNA probe revealed the presence of the 6.5-kb band diagnostic of the mutant allele.…”

mentioning

confidence: 99%

Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice.

Lieberman

Wiseman

Shi

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

335

244

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ABSTRACTy-Glutamyl transpeptidase (GGT) is an ectoenzyme that catalyzes the first step in the cleavage of glutathione (GSH) and plays an essential role in the metabolism of GSH and GSH conjugates of carcinogens, toxins, and eicosanoids. To learn more about the role of GGT in metabolism in vivo, we used embryonic stem cell technology to generate GGT-deficient (GGTml/GGTml) mice. GGTdeficient mice appear normal at birth but grow slowly and by 6 weeks are about half the weight of wild-type mice. They are sexually immature, develop cataracts, and have coats with a gray cast. Most die between 10 and 18 weeks. Plasma and urine GSH levels in the GGTml/GGTml mice are elevated 6-fold and 2500-fold, respectively, compared with wild-type mice. Tissue GSH levels are markedly reduced in eye, liver, and pancreas.Plasma cyst(e)ine levels in GGTm'/GGTml mice are reduced to '20% of wild-type mice. Oral administration of Nacetylcysteine to GGTml/GGTml mice results in normal growth rates and partially restores the normal agouti coat color. These findings demonstrate the importance of GGT and the y-glutamyl cycle in cysteine and GSH homeostasis.

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Spinal cord ischemia-induced elevation of amino acids: Extracellular measurement with microdialysis

Cited by 92 publications

References 30 publications

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA

Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice.

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