Article

Metabotropic glutamate receptor antagonists and agonists: potential neuroprotectors in diffuse brain injury.

Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China.
Journal of Clinical Neuroscience (impact factor: 1.25). 01/2007; 13(10):1023-7. DOI:10.1016/j.jocn.2005.11.042 pp.1023-7
Source: PubMed

ABSTRACT Our previous study has suggested that metabotropic glutamate receptors (mGluRs) were significantly involved in the secondary processes after diffuse brain injury (DBI) and that mGluRs antagonists or agonists may be used for the treatment of DBI. In the present study, the neuroprotective effects of antagonists or agonists of mGluRs on DBI were further investigated. Sprague-Dawly rats were randomized into the following six groups: (i) normal control; (ii) sham-operated control; (iii) DBI; (iv) DBI treated with normal saline (NS); (v) DBI treated with alpha-methyl-4-carboxy-phenylglycine (MCPG); and (vi) DBI treated with (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV). Animals were injected intracerebroventricularly (icv) with 10 microL MCPG (100mmol/L), DCG-IV (10nmol/L) or the equivalent volume of normal saline 1 h after injury. The neurological severity score (NSS), brain water content and the number of damaged neurons were determined 6, 12, 24, 72 and 168 h after injury. In rats with DBI, it was found that the NSS was improved and the water content in the frontal cortex and the number of damaged neurons in the parietal cortex were significantly reduced following icv injection of either MCPG or DCG-IV. This suggests that icv injection of the mGluR group I antagonist MCPG or the mGluR group II agonist DCG-IV may exert neuroprotective effects in the early stage after DBI.

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    Article: Glutamate receptor-mediated taurine release from the hippocampus during oxidative stress.
    Brian Tucker, James E Olson
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    ABSTRACT: Hippocampal slices swell and release taurine during oxidative stress. The influence of cellular signalling pathways on this process is unclear. Glutamate signalling can facilitate volume regulation in other CNS preparations. Therefore, we hypothesize activation of taurine release by oxidative stress results from tissue swelling and is coupled to activation of glutamate receptors. Rat hippocampi were incubated at room temperature for 2 hr in artificial cerebrospinal fluid (aCSF) equilibrated with 95% O2 plus 5% CO2. For some slices, 1 mM taurine was added to the aCSF to maintain normal tissue taurine content. Slices then were perfused with aCSF at 35 degrees C and baseline data recorded before 2 mM H2O2 was added. For some studies, mannitol or inhibitors of glutamate receptors or the volume-regulated anion channel (VRAC) were added before and during H2O2 treatment. The intensity of light transmitted through the slice (the intrinsic optical signal, IOS) was determined at 1-min intervals. Samples of perfusate were collected at 2-min intervals and amino acid contents determined by HPLC. Data were analyzed by repeated measures ANOVA and post hoc Dunnett's test with significance indicated for p<0.05. IOS of slices prepared without taurine treatment increased significantly by 3.3+/-1.3% (mean+/-SEM) during oxidative stress. Little taurine was detected in the perfusate of these slices and the rate of taurine efflux did not change during H2O2 exposure. The alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate antagonist, 25 microM CNQX, but not the N-methyl-D-aspartate (NMDA) receptor antagonist, 10 microM MK-801, inhibited the increase in IOS during H2O2 treatment. Taurine-treated slices exposed to H2O2 showed no change in IOS; however, taurine efflux increased by 335+/-178%. When these slices were perfused with hypertonic aCSF (350 mOsm) or exposed to the VRAC inhibitor, 20 microM DCPIB, no increase in the taurine efflux rate was observed during H2O2 exposure. Taurine-treated slices perfused with 10 microM MK-801 during H2O2 exposure showed a 4.6+/-1.9% increase in IOS but no increase in the taurine efflux rate. Taurine efflux via VRAC is critical for volume regulation of hippocampal slices exposed to oxidative stress. This increased taurine efflux does not result from direct activation of the taurine release pathway by H2O2. NMDA receptor activation plays an important role in taurine release during oxidative stress.
    Journal of Biomedical Science 01/2010; 17 Suppl 1:S10. · 2.01 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

10 microL MCPG
 
agonists
 
brain water content
 
diffuse brain injury
 
following six groups
 
frontal cortex
 
MCPG
 
metabotropic glutamate receptors
 
mGluR group
 
mGluR group II agonist DCG-IV
 
mGluRs antagonists
 
neurological severity score
 
neurons
 
neuroprotective effects
 
normal saline
 
normal saline 1 h
 
NS
 
parietal cortex
 
secondary processes
 
water content