**Author details**

and volume, HBOT improved both white and gray microstructures pointing to regeneration of nerve fibers. These micro structural changes correlate with the significant improvement in the memory, executive functions, information processing speed and global cognitive scores.

36 Hyperbaric Oxygen Treatment in Research and Clinical Practice - Mechanisms of Action in Focus

HBOT has been used as a primary or adjunctive therapy over the last 50 years, both in experimental and clinical studies. However, despite the decades of extensive research the entire spectrum of HBOT action is still not completely understood, although many mechanisms of its action have been proposed. Therefore, in this systematic review we elaborate the cellular and molecular mechanisms of HBOT actions. Based on the presented data it may be concluded that improved tissue oxygenation and cellular metabolism, anti-inflammation, anti-apoptosis, as well as intensifying of neuroplastic responses, promoting of synaptogenesis, neurogenesis and angiogenesis may constitute the multiple and complementary mechanisms underlying HBOT-induced neuroprotection. In addition, reduction of lipid peroxidation and up-regulation of antioxidant enzymes are among the mechanisms involved in the action of HBO. In that way, HBOT diminishes imbalance between oxidants and anti-oxidants that occurs after brain injury, and contributes to the maintenance of pro−/antioxidant homeostasis. Furthermore, HBOT effectively attenuates reactive astrogliosis and microgliosis, prevents tissue-damaging effects of neutrophils and suppresses formation of glial scar. Accordingly, by alleviating gliamediated inflammatory response and limiting production of inflammatory mediators HBOT fosters formation of more permissive environment for tissue repair, allowing the recovery of impaired brain functions. Overall, although results clearly suggest the validity of HBO therapy for the treatment of TBI, the underlying mechanism still needs to be studied in depth.

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant III 41014. The authors would like to thank the Center

The authors declare that there is no conflict of interests regarding the publication of this paper.

SP performed surgery and wrote the paper; SD was responsible for tissue preparation, immunohistochemistry and immunofluorescence; DK carried out the enzyme and lipid peroxidation

for Hyperbaric Medicine, Belgrade, Serbia for their continuous support.

**3. Conclusions**

**Acknowledgements**

**Conflict of interest**

**Authors' contribution**

Sanja Pekovic1 \*, Sanja Dacic<sup>2</sup> , Danijela Krstic<sup>3</sup> , Rada Jeremic4 , Marina Djelic4 and Predrag Brkic4

\*Address all correspondence to: spekovic@ibiss.bg.ac.rs

1 Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia

2 Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia

3 Institute of Medical Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

4 Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
