• Tamil S Anthonymuthu, Elizabeth M Kenny, Zachary E Hier, Clark Robert S B RSB Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburg, Patrick M Kochanek, Valerian E Kagan, and Hülya Bayır.
• Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA; Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA; Children's Neuroscience Institute, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
• Exp. Neurol. 2019 Jun 1; 316: 63-73.

AbstractCardiolipin (CL) is a mitochondria-specific phospholipid that is central to maintenance and regulation of mitochondrial bioenergetic and metabolic functions. CL molecular species display great tissue variation with brain exhibiting a distinct, highly diverse CL population. We recently showed that the appearance of unique brain-type CLs in plasma could serve as a brain-specific marker of mitochondrial/tissue injury in patients after cardiac arrest. Mitochondrial dysfunction has been increasingly implicated as a critical mechanism underlying the pathogenesis of traumatic brain injury (TBI). Therefore, we hypothesized that unique, brain-specific CL species from the injured brain are released to the peripheral circulation after TBI. To test this hypothesis, we performed a high-resolution mass spectrometry based phospholipidomics analysis of post-natal day (PND)17 rat brain and plasma after controlled cortical impact. We found a time-dependent increase in plasma CLs after TBI including the aforementioned brain-specific CL species early after injury, whereas CLs were significantly decreased in the injured brain. Compositional and quantitative correlational analysis suggested a possible release of CL into the systemic circulation following TBI. The identification of brain-type CLs in systemic circulation may indicate underlying mitochondrial dysfunction/loss after TBI. They may have potential as pharmacodynamics response biomarkers for targeted therapies.Copyright © 2019 Elsevier Inc. All rights reserved.

23 keywords...

hide…