Lipoic acid pretreatment attenuates ferric chloride-induced seizures in the rat.
Traumatic brain injury (TBI) is often complicated by the occurrence of seizures, which adversely affect clinical outcome. The risk of seizures increases to the extent that the injury is associated with sub-arachnoid hemorrhage and hematoma. A likely mechanism of seizure development post-TBI is decompartmentalization of iron from extravasated hemoglobin (Hb). It is well known that iron can catalyze formation of reactive oxygen species (ROS). Based on this proposed mechanism, a descriptive model of TBI-induced seizures, using intracortical injection of iron salts, was developed by Willmore. We have added modifications to enhance the quantifiability of seizure activity and have used the model to examine the therapeutic efficacy of lipoic acids (ROS-scavenging antioxidants). Male SD rats were pretreated with alpha-lipoic acid (ALA) and dihydrolipoic acid (DHLA) or appropriate vehicles. Under anesthesia, unilateral intracortical infusions of ferric chloride were performed stereotaxically. EEG was recorded via extradural electrodes. EEG was sampled for 10 s of every 60-s interval over a 24-h period following injection of ferric chloride. We measured the number of seconds of epileptiform discharges or seizure activity in every 10-s EEG sample during the 24 h. The EEGs of rats pretreated with ALA and DHLA exhibited 55% less seizure activity than vehicle-treated ferric chloride-injected animals, suggesting that lipoic acids may be of use in preventing or attenuating TBI-induced seizures.
Meyerhoff
James L
JL
Division of Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910-7500, USA. james.meyerhoff@na.amedd.army.mil
Lee
Jae K
JK
Rittase
Bradley W
BW
Tsang
Anne Y
AY
Yourick
Debra L
DL
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002712:Chlorides; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D005290:Ferric Compounds; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000975:Antioxidants; D002712:Chlorides; D005290:Ferric Compounds; D008063:Thioctic Acid; C015144:dihydrolipoic acid; C024555:ferric chloride