**3.4 Traumatic brain injury (TBI)**

Reducing excessive fission that occurs post-TBI is a potential target of neuroprotection to prevent neuronal impairments and death. In rodent models, TBI causes an increase in translocation of Drp1 to the mitochondria, increasing rates of fission. Consequently, this led to neuronal apoptosis, decreased neurogenesis, impaired cognition, and memory defects. When administered with Mdivi-1, a pharmacological inhibitor of Drp1, these negative effects were attenuated, confirming the role of increased Drp1 activity [95, 96]. Interestingly, Pietro's research group suggest that many molecular responses after severe TBI are opposite from that of mild TBI. Rodents with severe TBI presented with activation of fission as shown by overexpression of Drp1 and FIS1, a protein that binds to Drp1 for anchoring to the mitochondrial outer membrane. Furthermore, expressions of Mfn1 and Mfn2 were downregulated, and there were no changes in Opa1 gene and protein expressions, demonstrating an inhibition of fusion as a result of severe TBI. Additionally, the increase of dysfunctional mitochondria led to a subsequent overexpression of PINK1 and PARK2, triggering mitophagy. Conversely, mild TBI demonstrated activation of fusion with inhibition of fission; together, this did not change PINK1 or PARK2 gene expressions, thus showing no difference in mitophagy [97].
