Abstract
The present study was undertaken to investigate the effects of the α2 adrenergic agonist, clonidine, on the near complete cerebral ischemia (NCFI) evoked release of glutamate and aspartate from normo- and hyperglycemic rodent brain tissue using microdialysis tissue techniques. Hemodynamic variables, blood lactate, and glucose levels were monitored throughout the 40 min NCFI occlusion period. After 48 h, rats were killed and the extent of neuronal injury was determined in the cortex, striatum, and hippocampus. Hemodynamic variables recorded during ischemia improved with clonidine treatment in both normo- and hyperglycemic groups. Glutamate and aspartate levels were greatly increased over control values during normo- and hyperglycemic NCFI treatment. Clonidine pretreatment suppressed the release of both glutamate and aspartate during NCFI in normo- and hyperglycemic rodents when compared with NCFI-treated normo- and hyperglycemic rats without the drug. Significant neuroprotection of cells in the cortex, striatum, and hippocampus was also observed in drug-treated animals 48 h postischemia. The combined effects of diminished glutamate release after NCFI and reduced neuronal injury in both normo- and hyperglycemic states suggests that clonidine treatment during NCFI is neuroprotective. The neuroprotective effect of clonidine during ischemia may be ascribed to both a sensitization of central sympathetic activity and a reduced release of glutamate thereby reducing NMDA receptor activation and neuronal damage.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 526-534 |
| Number of pages | 9 |
| Journal | Experimental Brain Research |
| Volume | 167 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 2005 |
| Externally published | Yes |
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Keywords
- α2 agonists
- Glutamate
- Hyperglycemia
- Near complete forebrain ischemia
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
The effect of clonidine on cell survival, glutamate, and aspartate release in normo- and hyperglycemic rats after near complete forebrain ischemia. / Jellish, W. Scott; Murdoch, John; Kindel, Gisela; Zhang, Xin; White, Fletcher.
In: Experimental Brain Research, Vol. 167, No. 4, 12.2005, p. 526-534.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The effect of clonidine on cell survival, glutamate, and aspartate release in normo- and hyperglycemic rats after near complete forebrain ischemia
AU - Jellish, W. Scott
AU - Murdoch, John
AU - Kindel, Gisela
AU - Zhang, Xin
AU - White, Fletcher
PY - 2005/12
Y1 - 2005/12
N2 - The present study was undertaken to investigate the effects of the α2 adrenergic agonist, clonidine, on the near complete cerebral ischemia (NCFI) evoked release of glutamate and aspartate from normo- and hyperglycemic rodent brain tissue using microdialysis tissue techniques. Hemodynamic variables, blood lactate, and glucose levels were monitored throughout the 40 min NCFI occlusion period. After 48 h, rats were killed and the extent of neuronal injury was determined in the cortex, striatum, and hippocampus. Hemodynamic variables recorded during ischemia improved with clonidine treatment in both normo- and hyperglycemic groups. Glutamate and aspartate levels were greatly increased over control values during normo- and hyperglycemic NCFI treatment. Clonidine pretreatment suppressed the release of both glutamate and aspartate during NCFI in normo- and hyperglycemic rodents when compared with NCFI-treated normo- and hyperglycemic rats without the drug. Significant neuroprotection of cells in the cortex, striatum, and hippocampus was also observed in drug-treated animals 48 h postischemia. The combined effects of diminished glutamate release after NCFI and reduced neuronal injury in both normo- and hyperglycemic states suggests that clonidine treatment during NCFI is neuroprotective. The neuroprotective effect of clonidine during ischemia may be ascribed to both a sensitization of central sympathetic activity and a reduced release of glutamate thereby reducing NMDA receptor activation and neuronal damage.
AB - The present study was undertaken to investigate the effects of the α2 adrenergic agonist, clonidine, on the near complete cerebral ischemia (NCFI) evoked release of glutamate and aspartate from normo- and hyperglycemic rodent brain tissue using microdialysis tissue techniques. Hemodynamic variables, blood lactate, and glucose levels were monitored throughout the 40 min NCFI occlusion period. After 48 h, rats were killed and the extent of neuronal injury was determined in the cortex, striatum, and hippocampus. Hemodynamic variables recorded during ischemia improved with clonidine treatment in both normo- and hyperglycemic groups. Glutamate and aspartate levels were greatly increased over control values during normo- and hyperglycemic NCFI treatment. Clonidine pretreatment suppressed the release of both glutamate and aspartate during NCFI in normo- and hyperglycemic rodents when compared with NCFI-treated normo- and hyperglycemic rats without the drug. Significant neuroprotection of cells in the cortex, striatum, and hippocampus was also observed in drug-treated animals 48 h postischemia. The combined effects of diminished glutamate release after NCFI and reduced neuronal injury in both normo- and hyperglycemic states suggests that clonidine treatment during NCFI is neuroprotective. The neuroprotective effect of clonidine during ischemia may be ascribed to both a sensitization of central sympathetic activity and a reduced release of glutamate thereby reducing NMDA receptor activation and neuronal damage.
KW - α2 agonists
KW - Glutamate
KW - Hyperglycemia
KW - Near complete forebrain ischemia
UR - http://www.scopus.com/inward/record.url?scp=28244477368&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28244477368&partnerID=8YFLogxK
U2 - 10.1007/s00221-005-0064-4
DO - 10.1007/s00221-005-0064-4
M3 - Article
VL - 167
SP - 526
EP - 534
JO - Experimental Brain Research
JF - Experimental Brain Research
SN - 0014-4819
IS - 4
ER -