Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperIntravenous antiarrhythmic doses of lidocaine increase the survival rate of CA1 neurons and improve cognitive outcome after transient global cerebral ischemia in rats
Highlights
▶Ischemia during surgery can lead to neuronal damage and cognitive dysfunction. ▶Hippocampal CA1 pyramidal neurons are highly sensitive to injury from ischemia. ▶Lidocaine (i.v.) started before ischemia improves long-term CA1 neuronal survival. ▶ Lidocaine improves performance on the active place avoidance task after ischemia. ▶The active place avoidance cognitive task is dependent on functional CA1 neurons.
Section snippets
Experimental procedures
This study was approved by the Institutional Animal Care and Use Committee of the State University of New York Downstate Medical Center. Animals were allowed access to food and water before surgery. The minimal number of animals that assured statistical reliability were used and pain and suffering to the animals was minimized.
Assessment of hippocampal neuronal damage 7 days after global ischemia
In order to assess whether 2 mg/kg lidocaine improved recovery after global cerebral ischemia, we counted the number of intact neurons that stained for anti-NeuN in different brain regions. In sham rats, not subjected to ischemia, the mean number of intact CA1 pyramidal cells per 200 μm linear distance of the pyramidal cell layer was 36±1.3 (n=5). The number of intact CA1 pyramidal neurons per 200 μm 7 days after a 10-min period of global ischemia was 14±10.7 (n=10). Animals treated with 2
Discussion
An early study by our laboratory indicated the importance of Na influx in leading to anoxic neuronal damage and demonstrated that a selective Na channel blocker tetrodotoxin could be protective in brain slices (Boening et al., 1989). Lidocaine blocks Na channels and is used as a local anesthetic at high concentrations and an antiarrhythmic agent at low concentrations; in the current study we used an antiarrhythmic dose of lidocaine that has been shown to affect hypoxic neurons in brain slices (
Acknowledgments
The authors gratefully acknowledge the financial support of University Physicians of Brooklyn (Anesthesiology Department) and the State University of New York Downstate Medical Center.
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