Effects of exogenous creatine on population spike amplitude and on postanoxic hyperexcitability in brain slices.
In in vitro rat hippocampal slices, a short period of transient anoxia caused a lasting increase in the amplitude of the compound action potential (population spike, PS) that was evoked in CA1 by stimulation of the Schaffer collaterals. No such increase was seen over a comparable period of time in slices that were not subjected to anoxia. The appearance of such an increase was dependent on the duration of anoxia. Anoxia of 1 min duration did not cause any increase, anoxia lasting 2 min caused a nonsignificant increase, while 3 min of anoxia caused a lasting and statistically significant increase in PS amplitude. Addition of creatine, a compound that is known to afford protection against severe neuronal damage from longer periods of anoxia, prevented PS potentiation at a concentration of 10 mM, but not at a concentration of 1 mM. In addition, while 1 mM creatine by itself did not show any effect on PS amplitude of control slices, 10 mM creatine decreased PS amplitude also in such control slices, that had not been exposed to anoxia. These data demonstrate that this postanoxic hyperexcitability is caused by mechanisms that are little sensitive to the protection that in other contexts is provided by creatine. We suggest that understanding the mechanisms of postanoxic hyperexcitability may help understand the pathophysiology of the epileptic seizures that sometimes occur at the time of an ischemic stroke.
Parodi
Monica
M
Department of Neurosciences, Ophthalmology and Genetics, University of Genova, Via De Toni 5, 16132, Genoa, Italy.
Rebaudo
Renata
R
Perasso
Luisa
L
Gandolfo
Carlo
C
Cupello
Aroldo
A
Balestrino
Maurizio
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D003401:Creatine / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D003401:Creatine