Caspase-dependent cell death involved in brain damage after acute subdural hematoma in rats

B. Alessandri, T. Nishioka, A. Heimann, R. M. Bullock, O. Kempski

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Traumatic brain injury is associated with acute subdural hematoma (ASDH) that worsens outcome. Although early removal of blood can reduce mortality, patients still die or remain disabled after surgery and additional treatments are needed. The blood mass and extravasated blood induce pathomechanisms such as high intracranial pressure (ICP), ischemia, apoptosis and inflammation which lead to acute as well as delayed cell death. Only little is known about the basis of delayed cell death in this type of injury. Thus, the purpose of the study was to investigate to which extent caspase-dependent intracellular processes are involved in the lesion development after ASDH in rats. A volume of 300 μL blood was infused into the subdural space under monitoring of ICP and tissue oxygen concentration. To asses delayed cell death mechanisms, DNA fragmentation was measured 1, 2, 4 and 7 days after ASDH by TUNEL staining, and the effect of the pan-caspase inhibitor zVADfmk on lesion volume was assessed 7 days post-ASDH. A peak of TUNEL-positive cells was found in the injured cortex at day 2 after blood infusion (53.4 ± 11.6 cells/mm2). zVADfmk (160 ng), applied by intracerebroventricular injection before ASDH, reduced lesion volume significantly by more than 50% (vehicle: 23.79 ± 7.62 mm3; zVADfmk: 9.06 ± 4.08). The data show for the first time that apoptotic processes are evident following ASDH and that caspase-dependent mechanisms play a crucial role in the lesion development caused by the blood effect on brain tissue.

Original languageEnglish (US)
Pages (from-to)196-202
Number of pages7
JournalBrain Research
Volume1111
Issue number1
DOIs
StatePublished - Sep 21 2006

Keywords

  • Apoptotic cell death
  • Brain
  • Caspase inhibitor
  • Neuroprotection
  • Subdural hemorrhage

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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    Alessandri, B., Nishioka, T., Heimann, A., Bullock, R. M., & Kempski, O. (2006). Caspase-dependent cell death involved in brain damage after acute subdural hematoma in rats. Brain Research, 1111(1), 196-202. https://doi.org/10.1016/j.brainres.2006.06.105