Study of the effect of post-ischemic mild hypothermia on infarct size, apoptosis and inflammation in the endothelin-1 rat model of focal cerebral ischemia

An-Gaelle Ceulemans, An Van Hemelrijck, Said Hachimi-Idrissi, Sophie Sarre, Yvette Michotte

Research output: Chapter in Book/Report/Conference proceedingMeeting abstract (Book)

Abstract

Stroke is an important cause of morbidity and mortality in industrialized countries and thus far, few therapeutic compounds are effective to ameliorate the outcome of stroke. Only hypothermia has proven to be a robust neuroprotectant in several experimental animal stroke models; however the optimal therapeutic window is still not known. In our laboratory, the endothelin-1 (Et-1) rat model, in which Et-1 (a potent vasoconstrictor) is infused adjacent to the middle cerebral artery, is used as a model for transient focal cerebral ischemia and in a dose-dependent manner, a core and a penumbra of an insult can be distinguished. The core of the insult is represented by the striatum and the penumbra by the cortex. To investigate the effects of post-ischemic mild hypothermia, anaesthetized rats (with sevoflurane) are kept either under normothermic (37°C) or post-ischaemic mild hypothermic (34°C for 2 h) conditions. Previous research showed that post-ischemic mild hypothermia reduces the infarct volume almost by half and this reduction was correlated to the degree of apoptosis, 24 hours after the insult. Hypothermia reduced apoptosis (by a reduction in caspase-3 stained cells on paraffin embedded slices) and infarct size in the cortex, but it had little effect on the striatum. It has been suggested that hypothermia also inhibits pro-inflammatory cytokines (like IL-1_ and TNF-_) and induces anti-inflammatory cytokines (TGF-_). Therefore, we are currently investigating the effect of hypothermia on inflammation using ELISA and immunohistochemistry for these inflammatory markers. Thus, apoptosis and inflammation are examined 24 h, 72 h and one week after the ischemic insult. Using behavioural experiments (cylinder test, neurological deficit score), the effect of hypothermia on motor impairment is also investigated. The final objective is to determine the optimal time of onset and duration of hypothermia in the Et-1 rat model for focal cerebral ischemia, that can possibly be transferred to the clinical situation.
Original languageEnglish
Title of host publicationBelgian Society of Pharmaceutical Sciences, 13th forum of pharmaceutical sciences
Pages18
Number of pages1
Publication statusPublished - Oct 2008

Publication series

NameBelgian Society of Pharmaceutical Sciences, 13th forum of pharmaceutical sciences

Keywords

  • stroke
  • hypothermia
  • inflammation
  • endothelin-1

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