PT  - JOURNAL ARTICLE
AU  - Li Yang
AU  - Kaushik Shah
AU  - Hezhen Wang
AU  - Vardan T. Karamyan
AU  - Thomas J. Abbruscato
TI  - Characterization of Neuroprotective Effects of Biphalin, an Opioid Receptor Agonist, in a Model of Focal Brain Ischemia
AID  - 10.1124/jpet.111.184127
DP  - 2011 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 499--508
VI  - 339
IP  - 2
4099  - http://jpet.aspetjournals.org/content/339/2/499.short
4100  - http://jpet.aspetjournals.org/content/339/2/499.full
SO  - J Pharmacol Exp Ther2011 Nov 01; 339
AB  - Approximately 795,000 people experience a new or recurrent stroke in the United States annually. The purpose of this study was to assess the protective effect of a nonselective opioid receptor agonist, biphalin, in brain edema and infarct damage by using both in vitro and in vivo models of stroke. In an in vivo model of ischemia, biphalin significantly decreased edema (66.6 and 58.3%) and infarct (52.2 and 56.4%) ratios in mouse transient (60-min occlusion/24-h reperfusion) and permanent (6 h) middle cerebral artery occlusion models, respectively. Biphalin administration also showed decreased neurodegeneration in hippocampal, cortical, and striatal brain tissue after ischemia, evidenced by reduced Fluoro-Jade C staining. In addition, biphalin improved neurological function after stroke injury evidenced by neurological score and locomotor activity evaluation. Biphalin significantly decreased penumbral expression of Na+, K+, 2Cl− cotransporter (NKCC) and the translocation of the conventional isoforms of protein kinase C (PKC). It also reversed the activation of PKC-induced cell volume increase during ischemia in primary neuronal cell cultures exposed to 1 h of oxygen glucose deprivation. These data suggest that opioid receptor activation provides neuroprotection during stroke, and a possible explanation of this mechanism could be the inhibition of NKCC function via the regulation of PKC-dependent cell signaling.