Cyclooxygenase-2 in epilepsy.
Epilepsy is one of the more prevalent neurologic disorders in the world, affecting approximately 50 million people of different ages and backgrounds. Epileptic seizures propagating through both lobes of the forebrain can have permanent debilitating effects on a patient's cognitive and somatosensory brain functions. Epilepsy, defined by the sporadic occurrence of spontaneous recurrent seizures (SRS), is often accompanied by inflammation of the brain. Pronounced increases in the expression of key inflammatory mediators (e.g., interleukin -1β [IL-1β], tumor necrosis factor alpha [TNFα], cyclooxygenase-2 [COX-2], and C-X-C motif chemokine 10 [CXCL10]) after seizures may cause secondary damage in the brain and increase the likelihood of repetitive seizures. The COX-2 enzyme is induced rapidly during seizures. The increased level of COX-2 in specific areas of the epileptic brain can help to identify regions of seizure-induced brain inflammation. A good deal of effort has been expended to determine whether COX-2 inhibition might be neuroprotective and represent an adjunct therapeutic strategy along with antiepileptic drugs used to treat epilepsy. However, the effectiveness of COX-2 inhibitors on epilepsy animal models appears to depend on the timing of administration. With all of the effort placed on making use of COX-2 inhibitors as therapeutic agents for the treatment of epilepsy, inflammation, and neurodegenerative diseases there has yet to be a selective and potent COX-2 inhibitor that has shown a clear therapeutic outcome with acceptable side effects.
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, U.S.A.
Asheebo
A
Rojas
Jianxiong
J
Jiang
Thota
T
Ganesh
Myung-Soon
MS
Yang
Nadia
N
Lelutiu
Paoula
P
Gueorguieva
Raymond
R
Dingledine
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D019636:Neurodegenerative Diseases / Q000201:enzymology; D012640:Seizures / Q000188:drug therapy / Q000201:enzymology
D000927:Anticonvulsants; D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2
Anticonvulsant; Blood-brain barrier; Cognitive deficit; EP1; EP2; Neurodegeneration; Prostaglandin; Seizure