title: Time course of acute neuroprotective effects of lidocaine evaluated by brain impedanciometry in the global ischemia model.
abstract: Voltage-activated sodium channels play a primary role during ischemic brain edema and thus are a pharmacological target for therapy. Lidocaine, a sodium channel blocker, was tested in male Sprague-Dawley rats anesthetized with thiobarbital (60 mg·kg(-1) i.p.) and perfused i.v. with Ringer's solution (n = 9) or lidocaine (0.75 mg·kg(-1), n = 9, or 1.5 mg·kg(-1), n = 6). Two tungsten microelectrodes were implanted in the cerebral cortex to register changes in tissue impedance in response to the voltage fall of a square wave electric pulse (100 μA, 10 ms), before and after infusion of lidocaine or Ringer's solution and during global cerebral ischemia due to a respiratory arrest induced by D-tubocurarine. Lidocaine infusion under normoxic conditions did not change voltage values (Mann-Whitney U = 51; p > 0.05). In animals infused with Ringer's solution, the voltage fall induced by global cerebral ischemia was fast for ∼8 min at -8.0 ± 2.3%·min(-1) followed by a slow decay at -0.96 ± 0.17%·min(-1). The time constant of voltage decay (λ) was 215.6 s (F = 547.4; p = 0.00000). Voltage values of lidocaine-infused animals were significantly higher than those of rats infused with Ringer's solution (U = 100; p = 0.000089). The decay rates were -4.97 ± 1.36%·min(-1) (fast phase) and -1.04 ± 0.3%·min(-1) (slow phase) with λ = 672.5 s (+211.9%; p = 0.000000). These results suggest that lidocaine significantly reduced cerebral impedance, hence exerting a strong early anti-edema effect probably by blocking voltage-activated sodium channels.
authors: Laboratorio de Neurofisiología, Departamento de Ciencias Fisiológicas, Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela.
authors: R
authors: R
authors: Wix-Ramos
authors: A
authors: A
authors: Eblen-Zajjur
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D017097:Electric Impedance; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D008012:Lidocaine