Diltiazem Protects Human Nt-2 Neurons Against Excitotoxic Damage in a Model of Simulated Ischemia.
From: University of Veterinary Medicine Hannover, Cell Biology, Bischofsholer Damm 15/102, D-30173 Hannover, Germany. francois.paquet-durand@med.lu.se
Brain research
- Publish Date: Dec 2006
- ISSN: 0006-8993
- Volume: 1124
- Issue: 1
- Pages: 45-54
- Medium: Print
- Language: English
- Citation (JAMA): Paquet-Durand François, Gierse Andrea, Bicker Gerd, et al. Diltiazem Protects Human Nt-2 Neurons Against Excitotoxic Damage in a Model of Simulated Ischemia.. Brain Res. Dec 2006;1124:45-54
Abstract
In vitro models are often used to investigate pathophysiological mechanisms of brain cell injury as they occur for instance during cerebral ischemia. To analyze the efficacy of potential neuroprotective compounds, cell physiological experiments were performed in a recently improved culture system of human model neurons. The postmitotic neurons were generated from the human NT-2 teratocarcinoma cell line, using a cell sphere culture method to facilitate rapid terminal differentiation. We simulated ischemic conditions in cultures of purified NT-2 neurons and found that low doses of the antihypertensive drug diltiazem protected against excitotoxic neuronal damage in vitro. Experiments with primary cortical mouse neuron cultures demonstrated a similar response to simulated ischemia and confirmed the neuroprotective effect of diltiazem. Calcium imaging experiments showed that diltiazem reduced both NMDA- and glutamate-induced calcium influxes in NT-2 neurons suggesting that its neuroprotective effect is based on the inhibition of voltage-gated calcium channels. These results indicate that diltiazem is an effective blocker of glutamate-induced excitotoxicity. Moreover, we suggest that cell cultures of human model neurons can provide an important initial test system for drug development in stroke therapy.
Mesh Headings (Keywords): Animals, Animals, Newborn, Calcium, Cell Differentiation, Cell Hypoxia, Cell Survival, Cells, Cultured, Diltiazem, Drug Interactions, Glutamic Acid, Humans, Ischemia, Mice, N-Methylaspartate, Neurons, Neuroprotective Agents, Neurotoxins, Teratocarcinoma, Time Factors
Check for Full Text / PubMed Unique Identifier (PMID): 17070504
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.