Delta activity as an early indicator for soman-induced brain damage: a review.
The organophosphorus (OP) compound soman is known to produce long-lasting epileptic seizure activity and associated brain damage. The present paper reviews the findings of five recent studies that tentatively established correlations between the development of soman-induced neuropathology and some subtle changes in the electrocortigraphic (ECoG) power spectrum. It is important to note that the reported experiments have been performed independently by three different teams (France, The Netherlands, USA) in various animal models (rat, guinea-pig, cynomolgus monkey) through different protocols of intoxication, pharmacological environments, and methods for ECoG spectral analysis. Despite these disparities, the five studies show that a suistained shift of ECoG power toward the lowest frequency range, i.e. the delta band, occurs within the first hours of soman-induced seizures. This early ECoG spectral change is concurrent with the first neuropathological changes in brain and is almost constantly followed, days or weeks later, by at least minimal neuropathology. Moreover the relative contribution of delta activity to the ECoG power spectrum still remains abnormally high for 1-3 days after seizure onset, i.e. within the phase of damage maturation. On the other hand, somnan-induced neuropathology was not observed in non-seizuring animals in which the delta activity was not increased above the pre-soman baseline. Similarly, no brain damage was ever shown in seizuring subjects in which the initial delta change eventually normalized after the curative administration of efficient anticonvulsant drugs such as the non-competitive antagonists of the NMDA receptor. These results, in agreement with previously published observations, strongly suggest that an increase of the relative power in the delta band might be a real-time marker of the ongoing development of soman-induced, seizure-related cerebral lesions and a reliable predictor for the final neuronal losses to come. Therefore, the monitoring of delta activity during the 24-72 h period that follows soman exposure may potentially be a useful tool to follow "on-line" the progression of brain damage and to control the neuroprotective activity of'a medication. Moreover since the method is non-invasive in man and since the above-presented results have been partly found in primates, the applicability of spectral analysis as a prognostic means in human OP poisoning ought to be seriously considered.
Carpentier
P
P
Unité de Neuropharmacologie, Centre de Recherches du Service de Santé des Armées, La Tronche, France. 100437.201@compuserve.com
Foquin
A
A
Dorandeu
F
F
Lallement
G
G
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003700:Delta Rhythm / Q000187:drug effects*; D006801:Humans; D002534:Hypoxia, Brain / Q000139:chemically induced* / Q000503:physiopathology*; D012999:Soman / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D012999:Soman