**10. Conclusions**

Neuroprotective approaches are the focus for TBI management, particularly methods to classify and target specific mechanisms involved in the complex secondary-injury cascade. The literature shows that neuroprotective approaches historically have been dominated by a neurocentric view, making alteration of neuronal-based injury mechanisms the primary or exclusive focus of neuroprotective strategies. The data in the literature, therefore, stress the relevance of more broadly viewing injury as comprising endothelial, microglia, astroglia, oligodendroglia, and precursor cells. Recent neuroprotection methods describe this multifaceted structure and interplay, highlighting therapeutic approaches that stimulate the recovery and optimal functioning of non-neuronal cells and inhibit the underlying mechanism of neuronal cell death. Several encouraging, recently developed treatments include neuroprotective, neurorestorative, and anti-inflammatory agents (for example PEA formulations or biologics). In addition, researchers have reported the need for developing new neurothechnologies and the neuromarkers of brain injuries to enable a correct diagnosis and, as a result, appropriate selection of methods for neuropsychological rehabilitation including neurotherapy. However, due to the difficulty and heterogeneity of brain injuries, post-TBI neural therapies are still facing several challenges.

**Author Contributions:** All authors have read and agreed to the published version of the manuscript. R.C. and D.I. were involved in the design and intellectual concept of the study; M.C. performed the literature search. S.C. designed the study and critically revised the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** The writers would like to thank Maria Antonietta Medici for brilliant methodical assistance during this research, Francesco Soraci for office support and assistance, and also Valentina Malvagni for editorial assistance with the text.

**Conflicts of Interest:** Salvatore Cuzzocrea is a co-inventor on patent WO2013121449 A8 (Epitech Group Srl), which deals with methods and compositions for the modulation of amidases capable of hydrolyzing *N*-acylethanolamines that are employable in the treatment of inflammatory diseases. This invention is wholly unrelated to the present study. Moreover, Salvatore Cuzzocrea is also, with the Epitech Group, a co-inventor on the following patents: EP 2 821 083; MI2014 A001495; 102015000067344, that are unrelated to the study. The remaining authors report no conflict of interest.
