Metabotropic glutamate receptor antagonists and agonists: potential neuroprotectors in diffuse brain injury.
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.
Fei
Zhou
Z
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China. feizhou@fmmu.edu.cn
Zhang
Xiang
X
Bai
Hong-Min
HM
Jiang
Xiao-Fan
XF
Wang
Xi-Ling
XL
D000818:Animals; D001834:Body Water / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003521:Cyclopropanes / Q000494:pharmacology / Q000627:therapeutic use; D020833:Diffuse Axonal Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D007276:Injections, Intraventricular; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C104077:metabotropic glutamate receptor type 1; C474696:methyl-(4-carboxyphenyl)glycine; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005998:Glycine