Neuroprotective Efficacy of Taurolidine Against Depolarization Injury to CA1 Pyramidal Neurons in Rat Hippocampal Slices.
Abstract number :
3.038
Submission category :
Year :
2001
Submission ID :
1680
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
R.A. Wallis, M.D., Neurology, VA GLAHS and UCLA, Los Angeles, CA; K.L. Panizzon, J.D., Neurology, VA GLAHS and UCLA, Los Angeles, CA; R.D. Sofia, Ph.D., Carter-Wallace Inc., Cranbury, NJ
RATIONALE: Taurolidine is metabolized to taurine. Increses in taurine have been shown to decrease cell firing. Status epilepticus and excessive cellular firing has been linked to neuronal damage. Therefore, we examined the neuroprotective efficacy of taurolidine in a model of neuronal injury produced by depolarization.
METHODS: Using in vitro rat hippocampal slices, we monitored the CA1 orthodromic and antidromic population spike (PS) amplitude during depolarization injury produced by exposure to KCl 25 mM for 12 minutes. Taurolidine was given 30 minutes prior to KCl exposure and continued for 15 minutes, thereafter.
RESULTS: Taurolidine provided robust neuroprotection of CA1 PS amplitude in stimulated hippocampal slices subjected to depolarization-induced injury. At a taurolidine concentration of 30 mg/l CA1 orthodromic and antidromic PS amplitude recovered to 94.4% [plusminus] 2.9 and 94.6% [plusminus] 2.9, compared to unmedicated slices which recovered to only 10.9% [plusminus] 1.4, and 13.1% [plusminus] 0.9, respectively. Taurolidine treatment also provided protection against depolarization injury in unstimulated slices. This protection of unstimulated slices was similar to the protection observed with stimulated slices. Treatment with 30 mg/l taurolidine demonstrated a mean orthodromic and antidromic PS amplitude recovery of 95.1% [plusminus] 2.2 and 95.5% [plusminus] 1.9, respectively. Treatment with taurolidine 30 mg/l during depolarization injury also produced significant recovery of mean excitatory post-synaptic potential slope (91.7% [plusminus] 8.3) after depolarization when compared to paired, unmedicated slices which showed no recovety. Fiber volley response exhibited mild resistance to depolarization injury with a mean amplitude recovery of 31.7% [plusminus] 1.6 in paired, unmedicated slices. In contrast, treatment with taurolidine showed full recovery with a mean amplitude of 100% [plusminus] 0.
CONCLUSIONS: These studies demonstrate that taurolidine provides neuroprotection in an in vitro model of depolarization injury. In addition, these data suggest that taurine-enhancing therapies may be a useful strategy in the prevention of brain injury during status epilepticus.
Support: VA Research Service.
Disclosure: Grant - Carter-Wallace Inc., provided a research grant for another study using taurolidine, but not the present study. Materials - Carter-Wallace Inc., provided the taurolidine for this study