Heptanoate is neuroprotective in vitro but triheptanoin post-treatment did not protect against middle cerebral artery occlusion in rats. (14th September 2018)

• Record Type: Journal Article
• Authors: Tan, Kah Ni; Hood, Rebecca; Warren, Kirby; Pepperall, Debbie; Carrasco-Pozo, Catalina; Manzanero, Silvia; Borges, Karin; Spratt, Neil J.
• Is Part Of: Neuroscience letters. Volume 683(2018)
• Page Start: 207
• Page End: 214
• Publication Date: 2018-09-14
• Subjects: BHB β-hydryoxybutyrate -- CBF cerebral blood flow -- LCT long-chain triglyceride -- MCAo middle cerebral artery occlusion -- NMDA N-methyl-D-aspartate -- OCR oxygen consumption rate -- OGD oxygen glucose deprivation -- TCA tricarboxylic acid; Heptanoate -- Ischemic stroke -- MCAo -- Mitochondrial function -- Neuroprotection -- Triheptanoin; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.07.045
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Heptanoate pre-treatment is neuroprotective against oxygen glucose deprivation and NMDA in vitro . Heptanoate enhanced basal respiration, ATP turnover and proton leak in cultured astrocytes. Continuous infusion of triheptanoin (i.v.) initiated 1 h after stroke onset in rats did not alter stroke volume. Abstract: Triheptanoin, the medium-chain triglyceride of heptanoate, has been shown to be anticonvulsant and neuroprotective in several neurological disorders. In the gastrointestinal tract, triheptanoin is cleaved to heptanoate, which is then taken up by the blood and most tissues, including liver, heart and brain. Here we evaluated the neuroprotective effects of heptanoate and its effects on mitochondrial oxygen consumption in vitro . We also investigated the neuroprotective effects of triheptanoin compared to long-chain triglycerides when administered after stroke onset in rats. Heptanoate pre-treatment protected cultured neurons against cell death induced by oxygen glucose deprivation and N -methyl- D -aspartate. Incubation of cultured astrocytes with heptanoate for 2 h increased mitochondrial proton leak and also enhanced basal respiration and ATP turnover, suggesting that heptanoate protects against oxidative stress and is used as fuel. However, continuous 72 h infusion of triheptanoin initiated 1 h after middle cerebral artery occlusion in rats did not alter stroke volume at 3 days or neurological deficit at 1 and 3 days relative to long-chain triglyceride control treatment.