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Differential cerebral gene expression during cardiopulmonary bypass in the rat: evidence for apoptosis?

Publication ,  Journal Article
Sato, Y; Laskowitz, DT; Bennett, ER; Newman, MF; Warner, DS; Grocott, HP
Published in: Anesth Analg
June 2002

UNLABELLED: Cardiopulmonary bypass (CPB) is associated with a spectrum of cerebral injuries. The molecular changes in the brain that might contribute to these injuries are not clearly known. We sought to determine whether the expression of apoptotic genes is increased after CPB in the rat. Rats (n = 7) were subjected to 90 min of normothermic CPB. A group of sham-operated rats (n = 7) served as non-CPB controls. After a 3-h post-CPB period of recovery, their brains were removed, homogenized, and processed for messenger RNA (mRNA) extraction. By using a ribonuclease protection assay, the ratios of both pro- and antiapoptotic mRNA (bcl-x, bcl-2, bax, caspase 2, and caspase 3) to the housekeeping glyceraldehyde phosphate dehydrogenase (GAPDH) gene were determined. Additionally, Western immunoblotting was performed to detect the presence of activated caspase 3, a protein central in the apoptotic process. Compared with the non-CPB controls, the CPB group had significantly increased levels of apoptotic/GAPDH mRNA ratios (bcl-x, 0.414 +/- 0.152 CPB versus 0.251 +/- 0.051 non-CPB, P = 0.048; caspase 2, 0.030 +/- 0.014 CPB versus 0.018 +/- 0.005 non-CPB, P = 0.048; bax, 0.106 +/- 0.035 CPB versus 0.066 +/- 0.009 non-CPB, P = 0.009; bcl-2, 0.011 +/- 0.006 CPB versus 0.006 +/- 0.002 non-CPB, P = 0.035). However, no activated caspase 3 protein was detected in either group. Elucidating the molecular biological sequelae of CPB may aid in the understanding of the pathophysiology of cardiac surgery-associated cerebral injury and, in doing so, may be useful in identifying potential therapeutic targets for pharmacologic neuroprotection. IMPLICATIONS: Cardiopulmonary bypass (CPB) appears to induce transcription of pro- and antiapoptotic genes in the rat brain, but caspase-mediated apoptosis itself does not appear to be activated. Elucidating the molecular biological sequelae of CPB may aid in the understanding of the pathophysiology of cardiac surgery-associated cerebral injury and, in doing so, may be useful in identifying potential therapeutic targets for pharmacologic neuroprotection.

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Published In

Anesth Analg

DOI

ISSN

0003-2999

Publication Date

June 2002

Volume

94

Issue

6

Start / End Page

1389 / 1394

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Temperature
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Nuclease Protection Assays
  • Nerve Tissue Proteins
  • Male
  • Gene Expression Regulation
  • Cardiopulmonary Bypass
 

Citation

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Sato, Y., Laskowitz, D. T., Bennett, E. R., Newman, M. F., Warner, D. S., & Grocott, H. P. (2002). Differential cerebral gene expression during cardiopulmonary bypass in the rat: evidence for apoptosis? Anesth Analg, 94(6), 1389–1394. https://doi.org/10.1097/00000539-200206000-00003
Sato, Yukie, Daniel T. Laskowitz, Ellen R. Bennett, Mark F. Newman, David S. Warner, and Hilary P. Grocott. “Differential cerebral gene expression during cardiopulmonary bypass in the rat: evidence for apoptosis?Anesth Analg 94, no. 6 (June 2002): 1389–94. https://doi.org/10.1097/00000539-200206000-00003.
Sato Y, Laskowitz DT, Bennett ER, Newman MF, Warner DS, Grocott HP. Differential cerebral gene expression during cardiopulmonary bypass in the rat: evidence for apoptosis? Anesth Analg. 2002 Jun;94(6):1389–94.
Sato, Yukie, et al. “Differential cerebral gene expression during cardiopulmonary bypass in the rat: evidence for apoptosis?Anesth Analg, vol. 94, no. 6, June 2002, pp. 1389–94. Pubmed, doi:10.1097/00000539-200206000-00003.
Sato Y, Laskowitz DT, Bennett ER, Newman MF, Warner DS, Grocott HP. Differential cerebral gene expression during cardiopulmonary bypass in the rat: evidence for apoptosis? Anesth Analg. 2002 Jun;94(6):1389–1394.

Published In

Anesth Analg

DOI

ISSN

0003-2999

Publication Date

June 2002

Volume

94

Issue

6

Start / End Page

1389 / 1394

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Temperature
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Nuclease Protection Assays
  • Nerve Tissue Proteins
  • Male
  • Gene Expression Regulation
  • Cardiopulmonary Bypass