title: Intravenous antiarrhythmic doses of lidocaine increase the survival rate of CA1 neurons and improve cognitive outcome after transient global cerebral ischemia in rats.
abstract: Brain ischemia is often a consequence of cardiac or neurologic surgery. Prophylactic pharmacological neuroprotection would be beneficial for patients undergoing surgery to reduce brain damage due to ischemia. We examined the effects of two antiarrhythmic doses of lidocaine (2 or 4 mg/kg) on rats in a model of transient global cerebral ischemia. The occlusion of both common carotid arteries combined with hypotension for 10 min induced neuronal loss in the CA1 region of the hippocampus (18±12 vs. 31±4 neurons/200 μm linear distance of the cell body layer, X±SD; P<0.01). Lidocaine (4 mg/kg) 30 min before, during and 60 min after ischemia increased dorsal hippocampal CA1 neuronal survival 4 weeks after global cerebral ischemia (30±9 vs. 18±12 neurons/200 μm; P<0.01). There was no significant cell loss after 10 min of ischemia in the CA3 region, the dentate region or the amygdalae; these regions were less sensitive than the CA1 region to ischemic damage. Lidocaine not only increased hippocampal CA1 neuronal survival, but also preserved cognitive function associated with the CA1 region. Using an active place avoidance task, there were fewer entrances into an avoidance zone, defined by relevant distal room-bound cues, in the lidocaine groups. The untreated ischemic group had an average, over the nine sessions, of 21±12 (X±SD) entrances into the avoidance zone per session; the 4 mg/kg lidocaine group had 7±8 entrances (P<0.05 vs. untreated ischemic) and the non-ischemic control group 7±5 entrances (P<0.01 vs. untreated ischemic). Thus, a clinical antiarrhythmic dose of lidocaine increased the number of surviving CA1 pyramidal neurons and preserved cognitive function; this indicates that lidocaine is a good candidate for clinical brain protection.
authors.affiliation: Program in Neural and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Popp
authors.forename: B
authors.initials: B
authors.lastname: Lei
authors.forename: E
authors.initials: E
authors.lastname: Kelemen
authors.forename: A A
authors.initials: AA
authors.lastname: Fenton
authors.forename: J E
authors.initials: JE
authors.lastname: Cottrell
authors.forename: I S
authors.initials: IS
authors.lastname: Kass
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology; D003071:Cognition / Q000187:drug effects*; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008012:Lidocaine / Q000008:administration & dosage*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D008012:Lidocaine