Gabapentin suppresses cortical spreading depression susceptibility.
Cortical spreading depression (CSD) is an intense depolarization wave implicated in the pathophysiology of brain injury states and migraine aura. As Ca(v)2.1 channels modulate CSD susceptibility, we tested gabapentin, which inhibits Ca(v)2.1 through high-affinity binding to its alpha(2)delta subunit, on CSD susceptibility in anesthetized rats. Gabapentin, 100 or 200 mg/kg, elevated the electrical threshold for CSD and diminished recurrent CSDs evoked by topical KCl, when administered 1 hour before testing. With its favorable safety and tolerability profile, gabapentin may have a role in suppression of injury depolarizations in stroke, intracranial hemorrhage, and traumatic brain injury.
Hoffmann
Ulrike
U
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Dileköz
Ergin
E
Kudo
Chiho
C
Ayata
Cenk
C
D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000077206:Gabapentin; D018698:Glutamic Acid / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000588:Amines; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D000077206:Gabapentin; D018698:Glutamic Acid; D011189:Potassium Chloride; D005680:gamma-Aminobutyric Acid