Mechanisms of post-traumatic seizures: a quantum pharmacological analysis of the molecular properties of an epileptogenic focus following iron-induced membrane peroxidation.
Late post-traumatic epilepsy following severe head trauma has been well documented. While there is increasing evidence suggesting that iron-induced lipid peroxidation of neural membranes may accompany cerebral haemorrhage, the pathogenic processes of post-traumatic epileptogenesis remain unknown. Furthermore, the effective prophylactic use of standard anticonvulsant drugs is unsubstantiated. The rational design of therapeutic agents specific for the prevention and treatment of post-traumatic epilepsy hinges on understanding the molecular membrane events at the epileptogenic focus. This study employs the techniques of theoretical quantum pharmacology to provide a structural analysis of neural phospholipid membranes, investigating changes in membrane integrity at the epileptogenic focus as the molecular basis for seizure activity. Molecular mechanics calculations and molecular dynamics simulations were used to model the biochemical events of the epileptogenic focus. We predict that applications of quantum pharmacological techniques to model biochemical events may provide an understanding of proconvulsive pathogenic mechanisms in post-traumatic epilepsy.
Dakin
K A
KA
Department of Chemistry, Queen's University, Kingston, Ontario, Canada.
Weaver
D F
DF
D001224:Aspartic Acid / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D004834:Epilepsy, Post-Traumatic / Q000503:physiopathology*; D006801:Humans; D007501:Iron / Q000502:physiology*; D015227:Lipid Peroxidation / Q000502:physiology*; D008432:Mathematical Computing; D008563:Membrane Lipids / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008958:Models, Molecular; D008959:Models, Neurological; D010713:Phosphatidylcholines / Q000502:physiology; D010743:Phospholipids / Q000502:physiology; D011789:Quantum Theory; D013570:Synaptic Membranes / Q000502:physiology*
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D001224:Aspartic Acid; D007501:Iron