Treatment with an AMPA Antagonist 12 Hours following Severe Normothermic Forebrain Ischemia Prevents CA1 Neuronal Injury

Journal of Cerebral Blood Flow and Metabolism - Tập 13 Số 6 - Trang 933-939 - 1993
Hui Li1, Alastair M. Buchan1
1Neurology-Neuroscience, University of Ottawa, Ottawa Civic Hospital, Ottawa, Ontario, Canada

Tóm tắt

The neuroprotective effects of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo( f)quinoxaline (NBQX), GYKI 52466, and MK-801 were tested following severe forebrain ischemia. Wistar rats were subjected to 10 min of normothermic ischemia and reperfused for 7 days. Necrotic hippocampal CA1 neurons were counted and expressed as a percentage (mean ± SD). In Experiment 1, saline-treated rats sustained 81 ± 20% damage to dorsal CA1. Rats given NBQX 30 mg/kg i.p. x 3 lost 21 ± 27% (p < 0.01). Neither MK-801 1 mg i.p. x 3 alone, nor in combination with the cytoprotective dose of NBQX protected CA1, with 83 ± 18 and 54 ± 34% damage, respectively (NS). Giving NBQX 90 mg/kg i.v. did not protect cells (94 ± 5%) and resulted in nephrotoxicity. In Experiment 2, rats were given saline or three doses of NBQX 30 mg/kg i.p. immediately at reperfusion (RP) or after a 6-, 12-, or 24-h delay. Saline-treated rats suffered 79 ± 16% injury. NBQX given immediately resulted in 17 ± 17% injury, and even if treatment was delayed by either 6 or 12 h, there was marked protection with only 27 ± 32 and 25 ± 17% injury, respectively (all p < 0.01). Delaying the initiation of treatment to 24 h was not successful, resulting in 50 ± 28% injury (NS). In Experiment 3, saline-treated rats lost 81 ± 19% of CA1 cells, while those given GYKI 52466 10 mg/kg i.p. x 5 starting immediately following RP lost 80 ± 14%. Blocking α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors with NBQX postischemia is highly efficacious, indicating that delayed degeneration of CA1 cells is AMPA rather than N-methyl-d-aspartate (NMDA) receptor-linked and is reversible for CA1 cells for at least 12 h.

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Tài liệu tham khảo

10.1126/science.2403696

10.1038/jcbfm.1988.135

10.1038/jcbfm.1992.108

10.1111/j.1471-4159.1984.tb05396.x

10.1523/JNEUROSCI.10-01-00311.1990

10.1016/0304-3940(91)90314-J

10.1523/JNEUROSCI.11-04-01049.1991

10.1097/00001756-199108000-00016

10.1126/science.1317970

Cho S, 1991, J Cereb Blood Flow Metab, 11, S101

10.1016/0006-8993(90)91424-F

10.1111/j.1600-0404.1992.tb08052.x

10.1126/science.1849316

10.1523/JNEUROSCI.07-10-03343.1987

10.1016/0006-8993(92)90924-X

10.1126/science.1709304

10.1126/science.2899909

10.1126/science.1653450

10.1113/jphysiol.1990.sp018060

10.1016/0006-8993(82)90833-2

10.1016/0006-8993(92)90516-C

10.1038/357070a0

10.1126/science.256.5060.1217

10.1126/science.1317969

10.1038/jcbfm.1992.2

10.1097/00000542-199108000-00016

Nellgard B, 1991, Soc Neurosci Abst, 17, 184

10.1126/science.2660263

10.1126/science.1835799

10.1016/0304-3940(86)90136-9

10.1097/00001756-199108000-00011

10.1016/0304-3940(91)90115-A

Paxinos G, 1986, The Rat Brain in Stereotaxic Coordinates

10.1073/pnas.89.21.10499

10.1161/01.STR.10.3.267

10.1161/01.STR.19.7.913

Pulsinelli WA, 1992, Neurology, 42, 292

10.1002/ana.410110509

10.1126/science.2154034

10.1126/science.6093256

10.1161/01.STR.23.6.861

10.1126/science.1699275

10.1016/0092-8674(91)90568-J

Suzdak PD, 1990, Soc Neurosci Abst, 16, 1182

10.1007/978-94-011-2262-7_63

Tarnawa I, 1992, Acta Physiol Hung, 79, 163

10.1126/science.1710829

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Journal of Cerebral Blood Flow and Metabolism

Tập 13 Số 6

933-939

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