Research Unit of Experimental Neurotraumatology
Department of Neurosurgery
Medical University Graz
Neue Stiftingtalstraße 6
Website Muammer ÜCAL
”Combating the impaired energetics and hypoxia in traumatized brain – from subcellular mechanisms to systemic approaches”
Mammalian brain is almost exclusively dependent on the oxidative metabolism to meet the requirement of extensive energy demand. Several factors after a brain injury contribute to cerebral ischemia. The resulting lack of cerebral energy reserves and oxygen deprivation contributes to the detrimental secondary brain damage, in particular apoptotic and necrotic neuronal cell death. Whilst hypoxic insult reduces oxygen supply to the tissue, oxidative stress leads to mitochondrial damage, by which utilization of available oxygen gets even more difficult, resulting in deepened dysfunctional cellular energetics. Therefore, tissue oxygenation and cellular respiration are inseparable parts of one big pillar and we employed multiple approaches at subcellular and tissue levels to understand and attenuate hypoxia- and mitochondrial damage-associated secondary injury after TBI.
Despite the great body of literature pointing towards the detrimental effects of post-traumatic nitric oxide (NO) elevations in mitochondrial dysfunction, our results showed that the role of NO metabolism per se is limited or secondary. Mitochondrial stress, further, could be alleviated by targeting the glutamate node in the tricarboxylic acid (TCA) cycle independent of NO elevations. Whilst restoration of cellular respiration is a critical aspect, it also requires delivery of enough oxygen to the brain tissue and cells in order for it to fully serve the desired purpose. Repetitive hyperbaric oxygen (HBO) therapy in our work resulted in not only a significant improvement in the lesion size, which indicated a salvation of neuronal tissue from hypoxia, but also attenuated post traumatic demyelination and enhanced remyelination via upregulation of myelin basic protein (MBP). The latter observation clearly indicates the critical importance of long-term support to the oligodendroglia in order to facilitate effective remyelination.
Host & contact for questions: Helmut KUBISTA