TY - JOUR
T1 - Neuroprotective synergism of 2-amino-3-phosphonoproprionate (d,l-AP3) and MK-801 against ibotenate induced brain injury
AU - McDonald, John W.
AU - Johnston, Michael V.
PY - 1992/10/12
Y1 - 1992/10/12
N2 - The neuroprotective characteristics of the functional antagonist of metabotropic stimulated phosphoinositide hydrolysis, 2-amino-3-phosphonoproprionate (d,l-AP3), were examined alone and in combination with the non-competitive N-methyl-d-aspartate (NMDA) antagonist, MK-801, against ibotenate induced brain injury. Postnatal day (PND) 7 rats received unilateral stereotaxic intrastriatal injections of 10 nmol ibotenate and treated with either d,l-AP3 (600 nmol i.c.), MK-801 (1 mg/kg i.p.) or both. The severity of brain injury was assessed on PND 12 by comparison of the weights of injected and contralateral cerebral hemispheres. Ibotenate induced injury was partially reduced by treatment with MK-801 (34.0±4.4% protection, P<0.05 vs. PBS treated, independent t-test) but not d,l-AP3. However, combined treatment with both MK-801 and d,l-AP3 produced marked synergistic neuroprotection (83.5±7.6% protection, P<0.001 vs. PBS treated, independent t-test). The data suggest that metabotropic stimulated phosphoinositide hydrolysis contributes to excitotoxic neuronal injury in the presence of concurrent ionotropic receptor activation.
AB - The neuroprotective characteristics of the functional antagonist of metabotropic stimulated phosphoinositide hydrolysis, 2-amino-3-phosphonoproprionate (d,l-AP3), were examined alone and in combination with the non-competitive N-methyl-d-aspartate (NMDA) antagonist, MK-801, against ibotenate induced brain injury. Postnatal day (PND) 7 rats received unilateral stereotaxic intrastriatal injections of 10 nmol ibotenate and treated with either d,l-AP3 (600 nmol i.c.), MK-801 (1 mg/kg i.p.) or both. The severity of brain injury was assessed on PND 12 by comparison of the weights of injected and contralateral cerebral hemispheres. Ibotenate induced injury was partially reduced by treatment with MK-801 (34.0±4.4% protection, P<0.05 vs. PBS treated, independent t-test) but not d,l-AP3. However, combined treatment with both MK-801 and d,l-AP3 produced marked synergistic neuroprotection (83.5±7.6% protection, P<0.001 vs. PBS treated, independent t-test). The data suggest that metabotropic stimulated phosphoinositide hydrolysis contributes to excitotoxic neuronal injury in the presence of concurrent ionotropic receptor activation.
KW - 2-Amino-3-phosphonoproprionate
KW - Excitatory amino acid
KW - Excitotoxicity
KW - Ibotenate
KW - Metabotropic receptor
KW - Phosphoinositol
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=0026456603&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026456603&partnerID=8YFLogxK
U2 - 10.1016/0304-3940(92)90025-3
DO - 10.1016/0304-3940(92)90025-3
M3 - Article
C2 - 1361225
AN - SCOPUS:0026456603
SN - 0304-3940
VL - 145
SP - 213
EP - 216
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -