Pyruvate Dehydrogenase complex, metabolic enzymes, and energy derangement in traumatic brain injury

Traumatic brain injury (TBI) is a highly heterogeneous pathology ranging, in terms of outcome, from full recovery to death and characterized by variable changes of neurological functions, and of a plethora of biochemical/metabolic/molecular processes of cerebral cells. Following TBI, glucose dysmetabolism has been demonstrated in numerous laboratory and clinical studies. The pyruvate dehydrogenase complex (PDHC) is the multi-enzymatic system representing a crossroad allowing the prosecution of glucose catabolism, through the oxidative reactions within mitochondria. By converting pyruvate into acetyl-CoA, PDHC ensures the tricarboxylic acid cycle (TCA) priming, by fueling TCA with the substrate (acetyl-CoA) of the first cycle reaction. Notwithstanding PDHC has been recognized to be crucial in different pathologies, few data have been produced in models of TBI, with no studies on potential drugs targeting PDHC. In this chapter, we summarize the available data showing that PDHC plays a fundamental role in cerebral metabolism of TBI-injured brains.