Administration of a Sigma Receptor Agonist Delays MCAO-Induced Neurodegeneration and White Matter Injury

Christopher C. Leonardo, Aaron A. Hall, Lisa A. Collier, Suzanne M. Green, Alison E. Willing, Keith R. Pennypacker

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Many pharmacological treatments for stroke have afforded protection in rodent models but failed to show efficacy in clinical trials. This discrepancy may be due to the lack of long-term functional studies. Previously, delayed administration of the sigma receptor agonist 1,3-di-o-tolylguanidine (DTG) reduced infarct volume after middle cerebral artery occlusion (MCAO) in rats. The present study was conducted to determine whether the protective effects of DTG lead to improvements in behavioral functioning. Rats were subjected to MCAO and administered 7.5, 1.5, or 0.75 mg/kg DTG beginning 24 h post-surgery. Histological outcomes (96 h, 2 weeks, and 5 weeks) were compared with performance on a series of behavioral tests (2 and 4 weeks). Fluoro-Jade staining and immunohistochemistry were used to assess infarct volume and immune cell recruitment. All doses significantly reduced infarct volume and perturbation of striatal white matter tracts at 96 h. These reductions were associated with decreased numbers of CD11b-positive amoeboid microglia/macrophages. Despite short-term efficacy, DTG failed to improve behavioral outcomes or reduce infarct volumes after 96 h. While DTG may prove beneficial as a short-term therapy, these data highlight the importance of long-term functional recovery when evaluating novel therapies to treat stroke.

Original languageEnglish
Pages (from-to)135-145
Number of pages11
JournalTranslational Stroke Research
Issue number2
StatePublished - 2010

Bibliographical note

Funding Information:
Acknowledgements This work was supported in part by the National Institutes of Health (grant no. 5R21NS060907) and the American Heart Association (grant no. 0715096B).


  • Behavior
  • CNS
  • Inflammation
  • Ischemia
  • Rat
  • Therapy

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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