Chronic T cell infiltration is associated with inflammation and blood-brain barrier impairment during post-traumatic epileptogenesis
Abstract number :
1.008
Submission category :
1. Translational Research: 1A. Mechanisms / 1A1. Epileptogenesis of acquired epilepsies
Year :
2017
Submission ID :
349362
Source :
www.aesnet.org
Presentation date :
12/2/2017 5:02:24 PM
Published date :
Nov 20, 2017, 11:02 AM
Authors :
Xavier Ekolle Ndode-Ekane, A.I.V Institute, University of Eastern Finland; Liz Matthiesen, A.I.V Institute, University of Eastern Finland; Ivette Bañuelos Cabrera, A.I.V Institute, University of Eastern Finland; Cátia Palminha, A.I.V Institute, University
Rationale: Post-traumatic epilepsy occurs in about 11% of traumatic brain injury (TBI) patients. A major consequence of TBI is the infiltration of T cells into the brain. T cells play a role in epileptogenesis. Our objective is to identify the temporal profile of T cell infiltration into the cortex after TBI in rats and to determine whether it associates with the ongoing epileptogenic processes. Methods: TBI was induced in rats using the lateral fluid-percussion injury model. Post-TBI somatomotor deficits was assessed with neuroscore. Rats were killed at different time points and the brains processed for immunohistochemistry identification of T cells, microglial and macrophage activation and BBB impairment using anti-bodies against rat CD3, CD68 and IgG respectively. Results: In the perilesional cortex, the number of T cells was 444 folds above control values at 1 d post-injury (41 349 ± 7148 vs. 93 ± 29, p < 0.001). Their number doubled by 2 d (82 449 ± 15 502, p < 0.001). By 4 d post-TBI, there was a progressive drop, being 426 folds (39 626 ±18 001, p < 0.001), 46 folds at 7 d (4313 ± 1023, p < 0.001), 15 folds at 30 d (1416 ± 123, p < 0.001) and 21 folds at 90 (2036 ± 104, p < 0.001) as compared to controls. The high the number of T cells in the cortex, the poorer the recovery from the acute functional impairment (R = -0.538, P < 0.05). At the chronic phase, infiltrating T cells were localized to areas of activated microglial/ macrophage and blood-brain barrier (BBB) impairment. A multiple regression analysis showed that 48% of T cell infiltration can be accounted for by inflammation and BBB impairment (R = 0.695, F = 6.54, p < 0.05). Conclusions: This data demonstrates that T cell infiltration is most severe during the acute phase post-TBI and is associated with poor functional outcome. Furthermore, chronic T cell infiltration is associated with microglial activation and BBB impairment, suggesting that T cells may be involved in post-traumatic epileptogenesis. Funding: Funding from Academy of Finland
Translational Research