Abstract
Background and Purpose: Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed. Methods: Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n=5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 nig/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted. Results: Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean±SEM baseline, 1.86±0.25 pmol/ml perfusate; during ischemia, 8.14±0.89 pmol/ml; p<0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98±0.15 pmol/ml; ischemia, 24.4±5.93 pmol/ml; p<0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34±16 normal-appearing neurons, middle, 52.2±22.9 neurons; lateral, 56.6±21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6±6.5 neurons; middle, 131.4±4.9 neurons; lateral, 130±7.5 neurons; p<0.01 different from nontreated). Conclusions: Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.
| Original language | English |
|---|---|
| Pages (from-to) | 1595-1601 |
| Number of pages | 7 |
| Journal | Stroke |
| Volume | 23 |
| Issue number | 11 |
| State | Published - Nov 1 1992 |
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Keywords
- Cerebral ischemia
- Rats
- Ritanserin
- Serotonin
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Neuroscience(all)
Cite this
Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats. / Globus, Mordecai Y T; Wester, Per; Busto, Raul; Dalton Dietrich, W.
In: Stroke, Vol. 23, No. 11, 01.11.1992, p. 1595-1601.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats
AU - Globus, Mordecai Y T
AU - Wester, Per
AU - Busto, Raul
AU - Dalton Dietrich, W.
PY - 1992/11/1
Y1 - 1992/11/1
N2 - Background and Purpose: Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed. Methods: Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n=5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 nig/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted. Results: Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean±SEM baseline, 1.86±0.25 pmol/ml perfusate; during ischemia, 8.14±0.89 pmol/ml; p<0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98±0.15 pmol/ml; ischemia, 24.4±5.93 pmol/ml; p<0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34±16 normal-appearing neurons, middle, 52.2±22.9 neurons; lateral, 56.6±21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6±6.5 neurons; middle, 131.4±4.9 neurons; lateral, 130±7.5 neurons; p<0.01 different from nontreated). Conclusions: Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.
AB - Background and Purpose: Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed. Methods: Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n=5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 nig/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted. Results: Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean±SEM baseline, 1.86±0.25 pmol/ml perfusate; during ischemia, 8.14±0.89 pmol/ml; p<0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98±0.15 pmol/ml; ischemia, 24.4±5.93 pmol/ml; p<0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34±16 normal-appearing neurons, middle, 52.2±22.9 neurons; lateral, 56.6±21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6±6.5 neurons; middle, 131.4±4.9 neurons; lateral, 130±7.5 neurons; p<0.01 different from nontreated). Conclusions: Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.
KW - Cerebral ischemia
KW - Rats
KW - Ritanserin
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=0026470907&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026470907&partnerID=8YFLogxK
M3 - Article
C2 - 1279842
AN - SCOPUS:0026470907
VL - 23
SP - 1595
EP - 1601
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 11
ER -