Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats.

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 mg/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.

• Authors: M Y Globus, P Wester, R Busto, W D Dietrich
• Journal: Stroke (Stroke) Vol. 23 Issue 11 Pg. 1595-601 (Nov 1992) ISSN: 0039-2499 [Print] United States
• PMID: 1279842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Serotonin
• Hydroxyindoleacetic Acid

Topics

• Animals
• Brain Ischemia (metabolism, pathology)
• Cell Survival (physiology)
• Corpus Striatum (metabolism, pathology)
• Dialysis (methods)
• Extracellular Space (metabolism)
• Hippocampus (metabolism, pathology)
• Hydroxyindoleacetic Acid (metabolism)
• Male
• Neurons (pathology, physiology)
• Rats
• Rats, Wistar
• Serotonin (metabolism)