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 - Dietrich, W. Dalton
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1992/11
Y1 - 1992/11
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
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U2 - 10.1161/01.STR.23.11.1595
DO - 10.1161/01.STR.23.11.1595
M3 - Article
C2 - 1279842
AN - SCOPUS:0026470907
VL - 23
SP - 1595
EP - 1601
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 11
ER -