Vasospasm and p53-induced apoptosis in an experimental model of subarachnoid hemorrhage

Stroke. 2006 Jul;37(7):1868-74. doi: 10.1161/01.STR.0000226995.27230.96. Epub 2006 Jun 1.

Abstract

Background and purpose: Despite intensive research efforts, the etiology of vasospasm (sustained constriction of the cerebral vessels) remains unknown. In this study, we investigated the role of p53-induced apoptosis in the vasculature at 24 and 72 hours. To completely examine the apoptotic cascades, key proteins of the caspase-dependent, -independent and mitochondrial pathways were examined.

Methods: In this study, adult rats were divided into 3 groups: sham (n=21), nontreatment (subarachnoid hemorrhage [SAH]+dimethyl sulfoxide; n=42), and treatment (SAH+pifithrin-alpha) (n=42) groups. Each animal in the SAH group underwent a surgical procedure to induce SAH, and the basilar artery was harvested at 24 and 72 hours for analysis.

Results: We found severe vasospasm at the 24-hour time point, which persisted to 72 hours. Furthermore, we found that the markers of the apoptotic cascades rose significantly at the 24-hour time point but had dissipated by 72 hours. However, the neurological outcome and mortality scores improved at the 72-hour time point.

Conclusions: Apoptosis, and in particular p53, may play an important role in the etiology of vasospasm with relation to SAH, and in this model, vasospasm persisted to 72 hours, despite the fact that apoptosis does not.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / genetics
  • Basilar Artery / pathology
  • Benzothiazoles
  • Blood-Brain Barrier
  • Blotting, Western
  • Body Water
  • Brain / pathology
  • Brain Chemistry
  • Cerebrovascular Circulation
  • Male
  • Models, Animal
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Permeability
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Single-Blind Method
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / drug therapy
  • Subarachnoid Hemorrhage / pathology*
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use
  • Toluene / analogs & derivatives
  • Toluene / pharmacology
  • Toluene / therapeutic use
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / physiology*
  • Vasospasm, Intracranial / etiology
  • Vasospasm, Intracranial / pathology*

Substances

  • Apoptosis Regulatory Proteins
  • Benzothiazoles
  • Nerve Tissue Proteins
  • Thiazoles
  • Tumor Suppressor Protein p53
  • Toluene
  • pifithrin