Antiepileptic drugs as a possible neuroprotective strategy in brain ischemia.
Several new antiepileptic drugs (AEDs) have been introduced for clinical use recently. These new AEDs, as did the classic AEDs, target multiple cellular sites both pre- and postsynaptically. The major common goal of the pharmacological treatment using AEDs is to counteract abnormal brain excitability by either decreasing excitatory transmission or enhancing neuronal inhibition. Interestingly, an excessive release of excitatory amino acids and a reduced neuronal inhibition also occur in brain ischemia. Thus, recently, the use of AEDs as a possible neuroprotective strategy in brain ischemia is receiving increasing attention, and many AEDs have been tested in animal models of stroke, providing encouraging results. Experimental studies utilizing global or focal ischemia in rodents have provided insights into the possible neuroprotective action of the various AEDs. However, the implication of these studies in the treatment of acute stroke in humans is not always direct. In fact, various clinical studies with drugs targeting the same voltage- and ligand-gated channels modulated by most of the AEDs failed to show neuroprotection. The differential mechanisms that underlie the development of focal ischemic injury in experimental animal models versus human stroke require further investigation to open a new therapeutic perspective for neuroprotection that might be applicable in the future.
Calabresi
Paolo
P
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Italy. calabre@uniroma2.it
Cupini
Letizia M
LM
Centonze
Diego
D
Pisani
Francesco
F
Bernardi
Giorgio
G
D000208:Acute Disease; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009433:Neural Inhibition / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D000927:Anticonvulsants; D015220:Calcium Channels; D018696:Neuroprotective Agents; D015221:Potassium Channels; D018091:Receptors, AMPA; D018043:Receptors, Corticotropin; D015222:Sodium Channels; D018698:Glutamic Acid