Current knowledge on TDP-43 proteinopathy after single and repetitive traumatic brain injury available from in
| Single TBI (sTBI) | Repetitive TBI (rTBI) |
| Accumulation of the P-TDP-43 and U-TDP-43 cytosolic aggregates in neurons [220] | Two TBIs increase cytosolic P-TDP43 two-fold and three TBIs three-fold in neurons [220] |
| TDP-43 stress granules were not identified [237] | TDP-43 stress granules not found 24 h after the last rTBI; only detected in animals sacrificed immediately after the last repetitive trauma [237] |
| Blast TBI | |
| Cortical TDP-43 translocation to cytoplasm 1 dpi with TDP-43 fragmentation 1 and 7 dpi in the cortex [230] | Decrease in the TDP-43 expression after two TBIs and an increase in the expression of TDP-43 after three or four TBIs in the injured cortex 1 dpi, depending on the site of trauma application [239] |
| Changes in the TDP-43 expression in the injured cortex 1 dpi only at 16 psi blast overpressure over side; TDP-43 changes in other single TBI severities not detected [239] | |
| Diffuse TBI | |
| P-TDP-43 granules not found in the motor cortex [232] | TDP-43 translocation in neurons and microglia; TDP-43 fragmentation 1 dpi with phosphorylation 1 and 3 dpi in the frontal cortex [226] |
| TDP-43 translocation, fragmentation and phosphorylation changes not detected in the hippocampus 14 dpi [224] | |
| Focal TBI | |
| P-TDP-43 inclusions in the motor cortex at 3 dpi [232] | Increased TDP-43 expression in the cortical and hippocampal tissue 8 dpi [238] |
| TDP-43 fragmentation 3 and 7 dpi with decrease in total cell TDP-43 on 1, 3, 7 dpi; TDP-43 aggregates at 7 dpi in the cortical tissue with TDP-43 translocation in the astrocytes at 7 dpi [234] | P-TDP-43 inclusions in the motor cortex at 3 and 7 dpi [232] |
| TDP-43 fragmentation at 7 dpi and accumulation of cytosolic TDP-43 and its fragments two mpi in the injured cortex [39] | TDP-43 increase at 3 dpi in the cortex and 60 dpi in the hippocampus [235] |
| TDP-43 translocation to cytoplasm at 1 dpi and TDP-43 fragmentation at 3 and 7 dpi in the ipsilateral cortex [230] | |
| Increase in TDP-43 expression and its fragmentation at 12 dpi in the ipsilateral cortex [235] | |
| Lateral fluid percussion injury (LFPI) | |
| TDP-43 translocation in the cortical neurons and formation of P-TDP-43 at 7 dpi and 12 wpi in the cortex [223] | |
| TDP-43 fragmentation and phosphorylation of fragments at 1 and 7 dpi in the cortex [56] | |
| TDP-43 translocation in the cortical microglia and neurons at 3 dpi with TDP-43 fragmentation; P-TDP-43 formation at 14 dpi in the ipsilateral hippocampus [224] | |
| Human studies | |
| Phosphorylated TDP-43 aggregates in 3/62 acute and long-term TBI survivors, increased cytoplasmic TDP-43 in 86.9% |
TDP-43 proteinopathy in 80% of the 12 |
| TDP-43 immunoreactivity and cytoplasmic inclusions in a case of a single severe TBI with phosphorylated tau protein co-localized with TDP-43 [153] | Focal to widespread TDP-43 pathology found in 85% of 85 subjects with history of mild rTBI [164] |
| Nuclear phosphorylated TDP-43 fragments in patients surviving up to 3 days after TBI [56] | TDP-43 pathology with neuronal cytoplasmic inclusions detected in all |
| TDP-43 inclusions in neurons and glia in a case of CTE in a former football player [166] | |