T-cell infiltration into the perilesional cortex is long-lasting and associates with poor somatomotor recovery after experimental traumatic brain injury
Affiliations: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland
Correspondence:
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Corresponding author: Xavier Ekolle Ndode-Ekane, PhD, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland. Tel.: +358442707689; Fax: +358 17 16 3030; E-mail: xavier.ekollendode-ekane@uef.fi.
Abstract: Background:T-lymphocyte (T-cell) invasion into the brain parenchyma is a major consequence of traumatic brain injury (TBI). However, the role of T-cells in the post-TBI functional outcome and secondary inflammatory processes is unknown. We explored the dynamics of T-cell infiltration into the cortex after TBI to establish whether the infiltration relates to post-injury functional impairment/recovery and progression of the secondary injury. Method:TBI was induced in rats by lateral fluid-percussion injury, and the acute functional impairment was assessed using the neuroscore. Animals were killed between 1–90 d post-TBI for immunohistochemical analysis of T-cell infiltration (CD3), chronic macrophage/microglial reaction (CD68), blood-brain barrier (BBB) dysfunction (IgG), and endophenotype of the cortical injury. Furthermore, the occurrence of spontaneous seizures and spike-and-wave discharges were assessed using video-electroencephalography. Results:The number of T-cells peaked at 2-d post-TBI, and then dramatically decreased by 7-d post-TBI (5% of 2-d value). Unexpectedly, chronic T-cell infiltration at 1 or 3 months post-TBI did not correlate with the severity of chronic inflammation (p > 0.05) or BBB dysfunction (p > 0.05). Multiple regression analysis indicated that inflammation and BBB dysfunction is associated with 48% of the perilesional T-cell infiltration even at the chronic time-point (r = 0.695, F = 6.54, p < 0.05). The magnitude of T-cell infiltration did not predict the pathologic endophenotype of cortical injury, but the higher the number of T-cells in the cortex, the poorer the recovery index based on the neuroscore (r = – 0.538, p < 0.05). T-cell infiltration was not associated with the number or duration of age-related spike-and-wave discharges (SWD). Nevertheless, the higher the number of SWD, the poorer the recovery index (r = – 0.767, p < 0.5). Conclusions:These findings suggest that acute infiltration of T-cells into the brain parenchyma after TBI is a contributing factor to poor post-injury recovery.
