Introduction: Fatty acids can provide neuroprotection from cerebral ischemia. Palmitic methyl ester (PAME) is a 16-C fatty acid with vasodilatory properties while, stearic acid methyl ester (SAME), an 18-C fatty acid, is
simultaneously released from the autonomic ganglion and currently has no known function and has not been well explored. Since many neuro and/or vasoactive modulators have intrinsic neuroprotective properties, we investigated the possible neuroprotective effects of exogenous PAME/SAME in global (6mins of asphyxial cardiac arrest, ACA) and focal (middle cerebral artery occlusion with 2mins of reperfusion, MCAO) cerebral ischemia models. Since PAME (a potent vasodilator) is simultaneously released with SAME, we hypothesized that PAME/SAME can confer neuroprotection in rat models of focal/global cerebral ischemia.
Methods: Adult male Sprague-Dawley rats (250-350g) were fasted overnight before surgery and subsequently intubated and anesthesized. ACA and MCAO models were used to mimic ischemic conditions. For global ischemia, ACA (6mins) was performed 30mins after PAME/SAME treatment (0.02mg/kg, IV). Histopathology of hippocampal CA1 neurons was assessed 7 days after ACA. For focal ischemia, PAME or SAME was administered following reperfusion after 2hrs of MCAO. 2,3,5-triphenyltetrazolium staining of the brain was performed 24hrs after MCAO and the infarct volume was quantified.
Results: PAME (1143+/-39.3 normal neurons) or SAME (1188+/-57.8 normal neurons) pretreatment 30mins before ACA (6min) conferred neuroprotection in the CA1 region of the hippocampus 7 days after ACA as compared to no drug treatment (ACA only) or vehicle (0.005% ethanol). Additionally, SAME (15.97+/2.76%) and PAME (8.63+/-2.03%)-treated groups conferred reduction in percentage of brain infarct volume after MCAO as compared to controls.
Conclusions: PAME and SAME provide robust neuroprotection in both paradigms of ischemia. With proper timing and dosage, administration of PAME/SAME may one day prove to be an effective therapy against cerebral ischemia for at-risk patients.
Patient Care: We show that PAME and SAME confer neuroprotection in the setting of cerebral ischemia. PAME and SAME provide hippocampal neuroprotection and reduce brain infarction volume (regional neuroprotection). Mechanistic insight of PAME and SAME may prove valuable in the near future to protect against the detrimental effects of ischemic stroke in the clinical setting.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the role of stearic acids in neuroprotection, and 2) identify that PAMEand SAME can provide neuroprotection against focal and global cerebral ischemia.