Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia.

Abstract

We previously showed that palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Solutol HS15, a clinically approved excipient because it possesses similar fatty acid compositions as PAME/SAME. Asphyxial cardiac arrest (ACA, 6 min) was performed 30 min after PAME/SAME treatment (0.02 mg/kg, IV). Solutol HS15 (2 ml/kg, IP) was injected chronically for 14 days (once daily). Histopathology of hippocampal CA1 neurons was assessed 7 days after ACA. For focal ischemia experiments, PAME, SAME, or Solutol HS15 was administered following reperfusion after 2 h of middle cerebral artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium staining of the brain was performed 24 h after MCAO and the infarct volume was quantified. Following ACA, the number of surviving hippocampal neurons was enhanced by PAME-treated (68%), SAME-treated (69%), and Solutol-treated HS15 (68%) rats as compared to ACA only-treated groups. Infarct volume was decreased by PAME (83%), SAME (68%), and Solutol HS15 (78%) as compared to saline (vehicle) in MCAO-treated animals. PAME, SAME, and Solutol HS15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS15 is already administered as a solublizing agent to patients. With proper timing and dosage, administration of Solutol HS15 and PAME/SAME can be an effective therapy against cerebral ischemia.

• Authors: Hung Wen Lin, Isabel Saul, Victoria L Gresia, Jake T Neumann, Kunjan R Dave, Miguel A Perez-Pinzon
• Journal: Translational stroke research (Transl Stroke Res) Vol. 5 Issue 1 Pg. 109-17 (Feb 2014) ISSN: 1868-601X [Electronic] United States
• PMID: 24323706 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Palmitates
• Stearic Acids
• Vasodilator Agents
• Polyethylene Glycols
• Solutol HS 15
• methyl palmitate

Topics

• Animals
• Brain Ischemia (drug therapy)
• Disease Models, Animal
• Infarction, Middle Cerebral Artery (drug therapy)
• Male
• Neuroprotective Agents (therapeutic use)
• Palmitates (therapeutic use)
• Polyethylene Glycols (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Stearic Acids (therapeutic use)
• Vasodilator Agents (therapeutic use)