Blood mitochondrial enzymatic assay as a predictor of long-term outcome in severe traumatic brain injury.
Recent studies have observed the central role of mitochondrial dysfunction in severe traumatic brain injury (sTBI). One hundred and seven sTBI patients (18-65years old, presenting within 8hours of injury) were randomised for a placebo controlled phase II trial of progesterone with or without hypothermia. We serially analysed blood mitochondrial enzymes (Complex I [C1], Complex IV [C4] and pyruvate dehydrogenase complex [PDH]) using a dipstick assay at admission and 7days later for 37 patients, irrespective of assigned group. Favorable Glasgow Outcome Scale (GOS) at 1year was associated with admission C1 levels above 0.19μg, admission C4 levels above 0.19μg and day 7 C1 levels above 0.17μg, all per 25μl of blood. Unfavorable GOS at 1year was associated with admission serum PDH levels above 0.23μg/25μl of blood. Survivors at 1year had significantly higher admission serum C1 levels above 0.19μg/25μl and day 7 C1 levels above 0.17μg/25μl. To our knowledge this is the first clinical trial associating blood mitochondrial enzymes with long-term outcome in sTBI. Serial monitoring and optimisation of blood C1, C4 and PDH levels could aid in prognostication and potentially guide in using mitochondrial targeted therapies. Blood mitochondrial enzymatic assay might suggest global reduction-oxidation status.
Department of Neurosurgery, Room 715, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: sumitneuro@gmail.com.
Sumit
S
Sinha
Department of Neurosurgery, Room 715, All India Institute of Medical Sciences, New Delhi 110029, India.
Amol
A
Raheja
Department of Neurosurgery, Room 715, All India Institute of Medical Sciences, New Delhi 110029, India.
Neha
N
Samson
Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India.
Sanjeev
S
Bhoi
Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
Arul
A
Selvi
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Pushpa
P
Sharma
Department of Neurosurgery, Room 715, All India Institute of Medical Sciences, New Delhi 110029, India.
Bhawani Shankar
BS
Sharma
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000628:therapy; D042967:Electron Transport Complex I / Q000097:blood*; D003576:Electron Transport Complex IV / Q000097:blood*; D057075:Enzyme Assays; D005260:Female; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods; D008297:Male; D008875:Middle Aged; D011374:Progesterone / Q000627:therapeutic use; D011768:Pyruvate Dehydrogenase Complex / Q000097:blood*
D015415:Biomarkers; D011768:Pyruvate Dehydrogenase Complex; D011374:Progesterone; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I
Blood mitochondrial enzymes; Complex I; Complex IV; Predictors of outcome; Pyruvate dehydrogenase complex; Severe traumatic brain injury