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Extracellular brain cortical levels of noradrenaline in ischemia : - Effects of desipramine and postischemic administration of idazoxan

Gustafson, I. ; Westerberg, E. J. and Wieloch, T. LU (1991) In Experimental Brain Research 86(3). p.555-561
Abstract

Using microdialysis, extracellular noradrenaline (NA) levels in the rat cerebral cortex were studied under isoflurane/N2O anaesthesia before, during and for 6 hours following 10 min of forebrain ischemia in a 2-vessel occlusion model. A microdialysis probe was introduced into the parietal cortex and dorsal hippocampus in anaesthetized rats and continuously perfused with Krebs-Ringerbicarbonate buffer with or without the NA uptake inhibitor desipramine (DMI, 5 μM). Twenty min fractions were collected and the extracellular NA levels were measured in the dialysates using HPLC with electrochemical detection. The basal NA concentration in the dialysate was 10.5±1.8 (mean±SEM) pg/20 min fraction and increased to 39.3±4.8 pg/20 min... (More)

Using microdialysis, extracellular noradrenaline (NA) levels in the rat cerebral cortex were studied under isoflurane/N2O anaesthesia before, during and for 6 hours following 10 min of forebrain ischemia in a 2-vessel occlusion model. A microdialysis probe was introduced into the parietal cortex and dorsal hippocampus in anaesthetized rats and continuously perfused with Krebs-Ringerbicarbonate buffer with or without the NA uptake inhibitor desipramine (DMI, 5 μM). Twenty min fractions were collected and the extracellular NA levels were measured in the dialysates using HPLC with electrochemical detection. The basal NA concentration in the dialysate was 10.5±1.8 (mean±SEM) pg/20 min fraction and increased to 39.3±4.8 pg/20 min fraction after local administration of DMI. During ischemia, NA increased to 38 times the basal level without DMI, and 6 times with DMI included during two hours' perfusion prior to ischemia. After recirculation NA levels returned to, or even transiently decreased below, preischemic values. With DMI present in the dialysis buffer, administration of idazoxan immediately following ischemia delayed the return to preischemic NA levels in the recirculation phase. In the absence of DMI, no effect of idazoxan on postischemic levels of NA was found. Local administration of DMI increases basal extracellular NA levels and reduces the ischemia-induced NA release. The latter effect may be a due to inhibition of the NA uptake system working in a reversed mode, or as a result of decreased synthesis of NA due to activation of presynaptic α2-receptors by the increased synaptic NA levels. Postischemic treatment with the α2-adrenoceptor antagonist idazoxan in combination with DMI prolongs the period of elevated extracellular NA levels, which may be of importance for the protective properties of idazoxan against ischemic cell injury.

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type
Contribution to journal
publication status
published
subject
keywords
Cerebral ischemia, Desipramine, Idazoxan, Microdialysis, Noradrenaline, Rat
in
Experimental Brain Research
volume
86
issue
3
pages
555 - 561
publisher
Springer
external identifiers
  • pmid:1684752
  • scopus:0025873711
ISSN
0014-4819
DOI
10.1007/BF00230528
language
English
LU publication?
yes
id
140a17f2-7670-42a5-9f53-b274c4355fa4
date added to LUP
2019-06-13 16:34:25
date last changed
2021-01-03 06:32:41
@article{140a17f2-7670-42a5-9f53-b274c4355fa4,
  abstract     = {<p>Using microdialysis, extracellular noradrenaline (NA) levels in the rat cerebral cortex were studied under isoflurane/N<sub>2</sub>O anaesthesia before, during and for 6 hours following 10 min of forebrain ischemia in a 2-vessel occlusion model. A microdialysis probe was introduced into the parietal cortex and dorsal hippocampus in anaesthetized rats and continuously perfused with Krebs-Ringerbicarbonate buffer with or without the NA uptake inhibitor desipramine (DMI, 5 μM). Twenty min fractions were collected and the extracellular NA levels were measured in the dialysates using HPLC with electrochemical detection. The basal NA concentration in the dialysate was 10.5±1.8 (mean±SEM) pg/20 min fraction and increased to 39.3±4.8 pg/20 min fraction after local administration of DMI. During ischemia, NA increased to 38 times the basal level without DMI, and 6 times with DMI included during two hours' perfusion prior to ischemia. After recirculation NA levels returned to, or even transiently decreased below, preischemic values. With DMI present in the dialysis buffer, administration of idazoxan immediately following ischemia delayed the return to preischemic NA levels in the recirculation phase. In the absence of DMI, no effect of idazoxan on postischemic levels of NA was found. Local administration of DMI increases basal extracellular NA levels and reduces the ischemia-induced NA release. The latter effect may be a due to inhibition of the NA uptake system working in a reversed mode, or as a result of decreased synthesis of NA due to activation of presynaptic α<sub>2</sub>-receptors by the increased synaptic NA levels. Postischemic treatment with the α<sub>2</sub>-adrenoceptor antagonist idazoxan in combination with DMI prolongs the period of elevated extracellular NA levels, which may be of importance for the protective properties of idazoxan against ischemic cell injury.</p>},
  author       = {Gustafson, I. and Westerberg, E. J. and Wieloch, T.},
  issn         = {0014-4819},
  language     = {eng},
  number       = {3},
  pages        = {555--561},
  publisher    = {Springer},
  series       = {Experimental Brain Research},
  title        = {Extracellular brain cortical levels of noradrenaline in ischemia : - Effects of desipramine and postischemic administration of idazoxan},
  url          = {http://dx.doi.org/10.1007/BF00230528},
  doi          = {10.1007/BF00230528},
  volume       = {86},
  year         = {1991},
}