Sigma receptor activation reduces infarct size at 24 hours after permanent middle cerebral artery occlusion in rats

Craig T. Ajmo, Dionne O.L. Vernon, Lisa Collier, Keith R. Pennypacker, Javier Cuevas

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


The only available treatment for embolic stroke is recombinant tissue plasminogen activator, which must be administered within three hours of stroke onset. We examined the effects of 1,3-di-o-tolyguanidine (DTG), a high affinity sigma receptor agonist, as a potential treatment for decreasing infarct area at delayed time points. Rats were subjected to permanent embolic middle cerebral artery occlusion (MCAO) and allowed to recover before receiving subcutaneous injections of 15 mg/kg of DTG at 24, 48, and 72 hours. At 96 hours the rats were euthanized, and brains harvested and sectioned. Infarct areas were quantified at the level of the cortical/striatal and cortical/hippocampal regions in control (MCAO-only) and DTG treated animals using a marker for neurodegeneration, Fluoro-Jade. DTG treatment significantly reduced infarct area in both cortical/striatal and cortical/hippocampal regions by >80%, relative to control rats. These findings were confirmed by immunohistochemical experiments using the neuronal marker, mouse anti-neuronal nuclei monoclonal antibody (NeuN), which showed that application of DTG significantly increased the number of viable neurons in these regions. Furthermore, DTG blocked the inflammatory response evoked by MCAO, as indicated by decreases in the number of reactive astrocytes and activated microglia/macrophages detected by immunostaining for glial fibrillary acidic protein (GFAP) and binding of isolectin IB4, respectively. Thus, our results demonstrate that the sigma receptor-selective agonist, DTG, can enhance neuronal survival when administered 24 hr after an ischemic stroke. In addition, the efficacy of sigma receptors for stroke treatment at delayed time points is likely the result of combined neuroprotective and anti-inflammatory properties of these receptors.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalCurrent Neurovascular Research
Issue number2
StatePublished - May 2006


  • Anti-inflammation
  • Fluoro-jade
  • Infarction
  • Ischemia
  • Middle cerebral artery occlusion
  • Neuroprotection
  • Sigma receptors
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Sigma receptor activation reduces infarct size at 24 hours after permanent middle cerebral artery occlusion in rats'. Together they form a unique fingerprint.

Cite this