Poul Henning Jensen

Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers

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Standard

Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers. / Nørregaard, Annette; Jensen, Stine Skov; Kolenda, Jesper et al.

In: Neurotoxicity Research, Vol. 22, No. 1, 2012, p. 43-58.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Nørregaard, A, Jensen, SS, Kolenda, J, Aaberg-Jessen, C, Christensen, KG, Jensen, PH, Schrøder, H & Kristensen, BW 2012, 'Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers', Neurotoxicity Research, vol. 22, no. 1, pp. 43-58. https://doi.org/10.1007/s12640-011-9300-9

APA

Nørregaard, A., Jensen, S. S., Kolenda, J., Aaberg-Jessen, C., Christensen, K. G., Jensen, P. H., Schrøder, H., & Kristensen, B. W. (2012). Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers. Neurotoxicity Research, 22(1), 43-58. https://doi.org/10.1007/s12640-011-9300-9

CBE

Nørregaard A, Jensen SS, Kolenda J, Aaberg-Jessen C, Christensen KG, Jensen PH, Schrøder H, Kristensen BW. 2012. Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers. Neurotoxicity Research. 22(1):43-58. https://doi.org/10.1007/s12640-011-9300-9

MLA

Vancouver

Nørregaard A, Jensen SS, Kolenda J, Aaberg-Jessen C, Christensen KG, Jensen PH et al. Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers. Neurotoxicity Research. 2012;22(1):43-58. doi: 10.1007/s12640-011-9300-9

Author

Nørregaard, Annette ; Jensen, Stine Skov ; Kolenda, Jesper et al. / Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers. In: Neurotoxicity Research. 2012 ; Vol. 22, No. 1. pp. 43-58.

Bibtex

@article{37ec1ca8cbc142a183225bdc80aab97b,
title = "Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers",
abstract = "Effects of chemotherapeutics on glioma cell lines and spheroids are usually investigated without evaluating the effects of chemotherapeutics on normal brain tissue. To perform such investigations, the aim of this study was to establish a panel of markers for detection of general cell death and more specific neuronal and glial degeneration induced by chemotherapeutics in organotypic rat corticostriatal slice cultures. The slice cultures were exposed to the alkylating agents temozolomide (TMZ) and nimustine (ACNU), the tyrosine kinase inhibitor imatinib mesylate (IM) and the microtubule-destabilizing agent vincristine (VCR). Densitometric measurements of uptake of the fluorescent dye propidium iodide (PI) were used for quantifying cellular degeneration. Moreover, paraffin sections were hematoxylin eosine stained and immunostained for the neuronal marker microtubule-associated protein 2 (MAP2), the astroglial marker glial fibrillary acidic protein (GFAP), and the oligodendroglial marker p25α. The results showed that the supposed clinically relevant drug concentrations were non-toxic. However, a time dependent increase in PI uptake was observed for high drug concentrations, except for TMZ, where no toxicity was observed. Corresponding immunostaining showed loss of MAP2 and increased expression of GFAP and p25α for cultures exposed to 1,000 nM VCR. Cultures exposed to high concentrations of ACNU and IM disintegrated, leaving no tissue for histology. In conclusion, corticostriatal slice cultures and the established panel of markers represent an excellent tool for detecting toxicity induced by chemotherapeutics. Toxicity was not detected at clinical concentrations, but high concentrations with toxic effects were identified suggesting that some of the earlier identified anti-cancer effects are general cytotoxic effects and not specific anti-cancer effects.",
keywords = "Animals, Antineoplastic Agents, Biological Markers, Carrier Proteins, Cell Death, Dacarbazine, Glial Fibrillary Acidic Protein, Immunohistochemistry, Indicators and Reagents, Microtubule-Associated Proteins, Neuroglia, Neurons, Nimustine, Piperazines, Propidium, Pyrimidines, Rats, Vincristine",
author = "Annette N{\o}rregaard and Jensen, {Stine Skov} and Jesper Kolenda and Charlotte Aaberg-Jessen and Christensen, {Karina Garnier} and Jensen, {Poul Henning} and Henrik Schr{\o}der and Kristensen, {Bjarne Winther}",
year = "2012",
doi = "10.1007/s12640-011-9300-9",
language = "English",
volume = "22",
pages = "43--58",
journal = "Neurotoxicity Research",
issn = "1029-8428",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers

AU - Nørregaard, Annette

AU - Jensen, Stine Skov

AU - Kolenda, Jesper

AU - Aaberg-Jessen, Charlotte

AU - Christensen, Karina Garnier

AU - Jensen, Poul Henning

AU - Schrøder, Henrik

AU - Kristensen, Bjarne Winther

PY - 2012

Y1 - 2012

N2 - Effects of chemotherapeutics on glioma cell lines and spheroids are usually investigated without evaluating the effects of chemotherapeutics on normal brain tissue. To perform such investigations, the aim of this study was to establish a panel of markers for detection of general cell death and more specific neuronal and glial degeneration induced by chemotherapeutics in organotypic rat corticostriatal slice cultures. The slice cultures were exposed to the alkylating agents temozolomide (TMZ) and nimustine (ACNU), the tyrosine kinase inhibitor imatinib mesylate (IM) and the microtubule-destabilizing agent vincristine (VCR). Densitometric measurements of uptake of the fluorescent dye propidium iodide (PI) were used for quantifying cellular degeneration. Moreover, paraffin sections were hematoxylin eosine stained and immunostained for the neuronal marker microtubule-associated protein 2 (MAP2), the astroglial marker glial fibrillary acidic protein (GFAP), and the oligodendroglial marker p25α. The results showed that the supposed clinically relevant drug concentrations were non-toxic. However, a time dependent increase in PI uptake was observed for high drug concentrations, except for TMZ, where no toxicity was observed. Corresponding immunostaining showed loss of MAP2 and increased expression of GFAP and p25α for cultures exposed to 1,000 nM VCR. Cultures exposed to high concentrations of ACNU and IM disintegrated, leaving no tissue for histology. In conclusion, corticostriatal slice cultures and the established panel of markers represent an excellent tool for detecting toxicity induced by chemotherapeutics. Toxicity was not detected at clinical concentrations, but high concentrations with toxic effects were identified suggesting that some of the earlier identified anti-cancer effects are general cytotoxic effects and not specific anti-cancer effects.

AB - Effects of chemotherapeutics on glioma cell lines and spheroids are usually investigated without evaluating the effects of chemotherapeutics on normal brain tissue. To perform such investigations, the aim of this study was to establish a panel of markers for detection of general cell death and more specific neuronal and glial degeneration induced by chemotherapeutics in organotypic rat corticostriatal slice cultures. The slice cultures were exposed to the alkylating agents temozolomide (TMZ) and nimustine (ACNU), the tyrosine kinase inhibitor imatinib mesylate (IM) and the microtubule-destabilizing agent vincristine (VCR). Densitometric measurements of uptake of the fluorescent dye propidium iodide (PI) were used for quantifying cellular degeneration. Moreover, paraffin sections were hematoxylin eosine stained and immunostained for the neuronal marker microtubule-associated protein 2 (MAP2), the astroglial marker glial fibrillary acidic protein (GFAP), and the oligodendroglial marker p25α. The results showed that the supposed clinically relevant drug concentrations were non-toxic. However, a time dependent increase in PI uptake was observed for high drug concentrations, except for TMZ, where no toxicity was observed. Corresponding immunostaining showed loss of MAP2 and increased expression of GFAP and p25α for cultures exposed to 1,000 nM VCR. Cultures exposed to high concentrations of ACNU and IM disintegrated, leaving no tissue for histology. In conclusion, corticostriatal slice cultures and the established panel of markers represent an excellent tool for detecting toxicity induced by chemotherapeutics. Toxicity was not detected at clinical concentrations, but high concentrations with toxic effects were identified suggesting that some of the earlier identified anti-cancer effects are general cytotoxic effects and not specific anti-cancer effects.

KW - Animals

KW - Antineoplastic Agents

KW - Biological Markers

KW - Carrier Proteins

KW - Cell Death

KW - Dacarbazine

KW - Glial Fibrillary Acidic Protein

KW - Immunohistochemistry

KW - Indicators and Reagents

KW - Microtubule-Associated Proteins

KW - Neuroglia

KW - Neurons

KW - Nimustine

KW - Piperazines

KW - Propidium

KW - Pyrimidines

KW - Rats

KW - Vincristine

U2 - 10.1007/s12640-011-9300-9

DO - 10.1007/s12640-011-9300-9

M3 - Journal article

C2 - 22203610

VL - 22

SP - 43

EP - 58

JO - Neurotoxicity Research

JF - Neurotoxicity Research

SN - 1029-8428

IS - 1

ER -