Unilateral blood flow decrease induces bilateral and symmetric responses in the immature brain

Sonia Villapol, Philippe Bonnin, Sébastien Fau, Olivier Baud, Sylvain Renolleau, Christiane Charriaut-Marlangue

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The effects of hemodynamic changes in the developing brain have yet to be fully understood. The aim of this study was to explore the relationship between perturbations of the cerebral blood flow in the developing brain via unilateral hypoperfusion in P7 rats. As expected, nuclear caspase-3 (casp3) cleavage and DNA fragmentation were detected at 48 hours after stroke in the injured cortex. Surprisingly, casp3 was also cleaved in the contralateral cortex, although without cell death markers. Delayed (48 hours) casp3 cleavage without DNA fragmentation was also identified after unilateral common carotid artery occlusion, both in the hypoperfused cortex and the unaffected cortex, producing mirror images. Upstream calpain activation, caspase-2 cleavage, and mitochondrial cytochrome c release initiated casp3 cleavage, but did not produce preconditioning. The neuronal marker NeuN co-localized with cleaved casp3 in cortical layers II-III and VI and with gaba-amino butyric acid in layer III. Indeed, collateral supply was provided from the opposite side during carotid artery occlusion but not after reperfusion, and the number of cleaved casp3-positive cells significantly negatively correlated with the common carotid artery immediate reperfusion percentage. In summary, unilateral hypoperfusion, while insufficient to induce cell death, may active bilateral and symmetric casp3 in the P7 rat brain. Additionally, the opposite healthy hemisphere is altered due to the injury and thus should not be used as an internal control.

Original languageEnglish (US)
Pages (from-to)2111-20
Number of pages10
JournalAmerican Journal of Pathology
Volume175
Issue number5
DOIs
StatePublished - Nov 2009

Keywords

  • Animals
  • Animals, Newborn
  • Brain
  • Brain Ischemia
  • Caspase 3
  • Cerebrovascular Circulation
  • DNA Fragmentation
  • Female
  • Hemodynamics
  • Laser-Doppler Flowmetry
  • Male
  • Rats
  • Regional Blood Flow
  • Journal Article
  • Research Support, Non-U.S. Gov't

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