Time Course of Acute Neuroprotective Effects of Lidocaine Evaluated by Brain Impedanciometry in the Global Ischemia Model

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.