Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Diltiazem protects human NT-2 neurons against excitotoxic damage in a model of simulated ischemia

Paquet-Durand, Francois LU ; Gierse, Andrea and Bicker, Gerd (2006) In Brain Research 1124. p.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... (More)
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. (c) 2006 Elsevier B.V. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MK801, neuroprotection, Ntera 2, calcium channel, excitotoxicity, stroke
in
Brain Research
volume
1124
pages
45 - 54
publisher
Elsevier
external identifiers
  • wos:000243016800007
  • scopus:33751182616
ISSN
1872-6240
DOI
10.1016/j.brainres.2006.09.077
language
English
LU publication?
yes
id
32e1b6ee-f5a1-412e-87c2-1f82cc7a7ea6 (old id 681964)
date added to LUP
2016-04-01 12:23:08
date last changed
2021-09-29 02:14:07
@article{32e1b6ee-f5a1-412e-87c2-1f82cc7a7ea6,
  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. (c) 2006 Elsevier B.V. All rights reserved.},
  author       = {Paquet-Durand, Francois and Gierse, Andrea and Bicker, Gerd},
  issn         = {1872-6240},
  language     = {eng},
  pages        = {45--54},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Diltiazem protects human NT-2 neurons against excitotoxic damage in a model of simulated ischemia},
  url          = {http://dx.doi.org/10.1016/j.brainres.2006.09.077},
  doi          = {10.1016/j.brainres.2006.09.077},
  volume       = {1124},
  year         = {2006},
}