PMID- 15099683
OWN - NLM
STAT- MEDLINE
DCOM- 20040802
LR  - 20131121
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 125
IP  - 3
DP  - 2004
TI  - Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size 
      after transient focal cerebral ischemia in rats.
PG  - 691-701
AB  - Lidocaine is a local anesthetic and antiarrhythmic agent. Although clinical and 
      experimental studies have shown that an antiarrhythmic dose of lidocaine can 
      protect the brain from ischemic damage, the underlying mechanisms are unknown. In 
      the present study, we examined whether lidocaine inhibits neuronal apoptosis in 
      the penumbra in a rat model of transient focal cerebral ischemia. Male Wistar 
      rats underwent a 90-min temporary occlusion of middle cerebral artery. Lidocaine 
      was given as an i.v. bolus (1.5 mg/kg) followed by an i.v. infusion (2 mg/kg/h) 
      for 180 min, starting 30 min before ischemia. Rats were killed and brain samples 
      were collected at 4 and 24 h after ischemia. Apoptotic changes were evaluated by 
      immunohistochemistry for cytochrome c release and caspase-3 activation and 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) for 
      DNA fragmentation. Cytochrome c release and caspase-3 activation were detected at 
      4 and 24 h after ischemia and DNA fragmentation was detected at 24 h. 
      Double-labeling with NeuN, a neuronal marker, demonstrated that cytochrome c, 
      caspase-3, and TUNEL were confined to neurons. Lidocaine reduced cytochrome c 
      release and caspase-3 activation in the penumbra at 4 h and diminished DNA 
      fragmentation in the penumbra at 24 h. Lidocaine treatment improved early 
      electrophysiological recovery and reduced the size of the cortical infarct at 24 
      h, but had no significant effect on cerebral blood flow in either the penumbra or 
      core during ischemia. These findings suggest that lidocaine attenuates apoptosis 
      in the penumbra after transient focal cerebral ischemia. The infarct-reducing 
      effects of lidocaine may be due, in part, to the inhibition of apoptotic cell 
      death in the penumbra.
FAU - Lei, B
AU  - Lei B
AD  - Department of Anesthesiology, State University of New York Downstate Medical 
      Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
FAU - Popp, S
AU  - Popp S
FAU - Capuano-Waters, C
AU  - Capuano-Waters C
FAU - Cottrell, J E
AU  - Cottrell JE
FAU - Kass, I S
AU  - Kass IS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 9007-43-6 (Cytochromes c)
RN  - 98PI200987 (Lidocaine)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/physiology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cerebral Infarction/*drug therapy/pathology/physiopathology
MH  - Cerebrovascular Circulation/drug effects/physiology
MH  - Cytochromes c/metabolism
MH  - DNA Fragmentation/drug effects/physiology
MH  - Disease Models, Animal
MH  - In Situ Nick-End Labeling
MH  - Infarction, Middle Cerebral Artery/drug therapy/pathology/physiopathology
MH  - Ischemic Attack, Transient/*drug therapy/pathology/physiopathology
MH  - Lidocaine/*pharmacology/therapeutic use
MH  - Male
MH  - Nerve Degeneration/*drug therapy/pathology/physiopathology
MH  - Rats
MH  - Rats, Wistar
MH  - Reaction Time/drug effects/physiology
MH  - Recovery of Function/drug effects/physiology
MH  - Treatment Outcome
EDAT- 2004/04/22 05:00
MHDA- 2004/08/03 05:00
CRDT- 2004/04/22 05:00
PHST- 2004/02/24 00:00 [accepted]
PHST- 2004/04/22 05:00 [pubmed]
PHST- 2004/08/03 05:00 [medline]
PHST- 2004/04/22 05:00 [entrez]
AID - S030645220400140X [pii]
AID - 10.1016/j.neuroscience.2004.02.034 [doi]
PST - ppublish
SO  - Neuroscience. 2004;125(3):691-701. doi: 10.1016/j.neuroscience.2004.02.034.