Brain Res. 2004 Aug 6;1016(2):139-44. Related Articles, Links
Lipoic acid pretreatment attenuates ferric chloride-induced seizures in the
rat.
Meyerhoff JL, Lee JK, Rittase BW, Tsang AY, Yourick DL.
Division of Neuroscience, Walter Reed Army Institute of Research, 503 Robert
Grant Ave., Silver Spring, MD 20910-7500, USA.
[email hidden]
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.
PMID: 15246849 [PubMed - in process]
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