Blood-Brain Barrier Disruption, HSP70 Expression and Apoptosis Due to 3-Nitropropionic Acid, a Mitochondrial Toxin

S. Sato, G. T. Gobbel, Y. Li, T. Kondo, K. Murakami, M. Sato, K. Hasegawa, J. Ch Copin, J. Honkaniemi, Frank R Sharp, P. H. Chan

Research output: Contribution to journalArticle

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Abstract

3-Nitropropionic acid (3-NP), a mitochondrial toxin, induces apoptosis in the striatum. We wanted to determine it there was a relationship between mitochondrial dysfunction, disruption of the blood-brain barrier (BBB), and apoptosis. BBB disruption following intrastriatal injection of 3-NP was assessed by Evans blue leakage, brain water content, and by the expression of the 70 kDa heat shock protein (HSP70) and mRNA. Apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated uridine 5′- triphosphate-biotin nick end labeling (TUNEL) and gel electrophoresis to detect internucleosomal DNA fragmentation. Microscopic evidence of Evans blue leakage due to 3-NP was present only 3 hr after injection. Both internucleosomal DNA fragmentation and TUNEL-labeling did not appear until 24 hr after injection. HSP70 (protein and mRNA) was also elevated by 24 hr. There was a quantitative increase in Evans blue leakage and brain water content due to 3-NP by 3 days after injection. Our results suggest that BBB disruption is an early event followed by increased HSP70 expression and apoptosis. We speculate that 3-NP damages endothelial cells, leading to vasogenic edema and apoptosis.

Original languageEnglish (US)
Pages (from-to)237-239
Number of pages3
JournalActa Neurochirurgica, Supplement
Volume1997
Issue number70
StatePublished - 1997
Externally publishedYes

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Keywords

  • 3-nitropropionic acid
  • Apoptosis
  • Blood-brain barrier
  • HSP70 expression

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Neurology

Cite this

Sato, S., Gobbel, G. T., Li, Y., Kondo, T., Murakami, K., Sato, M., Hasegawa, K., Copin, J. C., Honkaniemi, J., Sharp, F. R., & Chan, P. H. (1997). Blood-Brain Barrier Disruption, HSP70 Expression and Apoptosis Due to 3-Nitropropionic Acid, a Mitochondrial Toxin. Acta Neurochirurgica, Supplement, 1997(70), 237-239.