Time course of changes in lipid peroxidation, pre- and postsynaptic cholinergic indices, NMDA receptor binding and neuronal death in the gerbil hippocampus following transient ischemia.

Abstract

Brief (5 min) bilateral carotid occlusion in the gerbil produces forebrain ischemia resulting, as previously reported, in almost complete neuronal loss in the CA1 region of the hippocampus; this neuronal destruction occurs between the 4th and 7th day post-ischemia. Various hippocampal biochemical indices were measured from just after such ischemia to 21 days of recirculation, and the temporal pattern of changes compared with that of cell loss. The level of thiobarbiturate reacting substances (TBARS), a measure of lipid peroxidation, was greatly elevated at 30 min after ischemia, rapidly returned to normal levels (by 60 min), but was again elevated on days 4-14. The beginning of this second period of elevation correlated closely with the onset of neuronal loss and the very abrupt and large (to about 32%) decrease in specific N-methyl-D-aspartate (NMDA) binding sites, measured with radioactive CPP. The number of muscarinic binding sites, measured with radioactive quinuclidinyl benzilate, showed an even greater decrease (to 13%) at 21 days post-ischemia, but the decrease was delayed (starting at day 7) and much more gradual than the loss in NMDA binding. In neither case was there any change in binding affinity at any time studied. Acetylcholine (ACh) concentrations were initially greatly decreased (to about 15% at 5 min), transiently increased (to about 130% at 30 min), and then decreased again (to about 15% at 60 min), after which gradual recovery occurred and was completed by day 14. Since no inhibition of choline acetyltransferase activity was observed at any time, the reversible depression in ACh must depend upon some factor other than loss of this key synthetic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: K Haba, N Ogawa, K Mizukawa, A Mori
• Journal: Brain research (Brain Res) Vol. 540 Issue 1-2 Pg. 116-22 (Feb 01 1991) ISSN: 0006-8993 [Print] Netherlands
• PMID: 1829014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Receptors, N-Methyl-D-Aspartate
• Quinuclidinyl Benzilate
• 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
• Acetylcholinesterase

Topics

• Acetylcholinesterase (analysis)
• Animals
• Gerbillinae
• Hippocampus (pathology, physiology, physiopathology)
• Ischemic Attack, Transient (pathology, physiopathology)
• Kinetics
• Lipid Peroxidation
• Neurons (pathology, physiology)
• Piperazines (metabolism)
• Pyramidal Tracts (pathology, physiopathology)
• Quinuclidinyl Benzilate (metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Reference Values
• Synapses (physiology)
• Time Factors