Journal
BIOMEDICINES
Volume 10, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines10112721
Keywords
epilepsy; traumatic brain injury; magnetic resonance imaging; cognitive dysfunction; hippocampus
Categories
Funding
- European Union [602102]
- Academy of Finland [272249, 273909, 2285733-9, 275453, 284544, 312686, 316258, 298007]
- National Institute of Neurological Disorders and Stroke (NINDS) Center without Walls of the National Institutes of Health (NIH) [U54NS100064]
- Sigrid Juselius Foundation
- Alfred Kordelin Foundation [200276]
- Academy of Finland (AKA) [284544, 312686, 273909, 273909, 284544, 312686] Funding Source: Academy of Finland (AKA)
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A multiparametric MRI analysis along the septotemporal hippocampal axis can predict the development of post-traumatic epilepsy and cognitive impairment, and aid in the selection of subjects for preclinical trials of cognition-improving interventions.
It is necessary to develop reliable biomarkers for epileptogenesis and cognitive impairment after traumatic brain injury when searching for novel antiepileptogenic and cognition-enhancing treatments. We hypothesized that a multiparametric magnetic resonance imaging (MRI) analysis along the septotemporal hippocampal axis could predict the development of post-traumatic epilepsy and cognitive impairment. We performed quantitative T-2 and T-2* MRIs at 2, 7 and 21 days, and diffusion tensor imaging at 7 and 21 days after lateral fluid-percussion injury in male rats. Morris water maze tests conducted between 35-39 days post-injury were used to diagnose cognitive impairment. One-month-long continuous video-electroencephalography monitoring during the 6th post-injury month was used to diagnose epilepsy. Single-parameter and regularized multiple linear regression models were able to differentiate between sham-operated and brain-injured rats. In the ipsilateral hippocampus, differentiation between the groups was achieved at most septotemporal locations (cross-validated area under the receiver operating characteristic curve (AUC) 1.0, 95% confidence interval 1.0-1.0). In the contralateral hippocampus, the highest differentiation was evident in the septal pole (AUC 0.92, 95% confidence interval 0.82-0.97). Logistic regression analysis of parameters imaged at 3.4 mm from the contralateral hippocampus's temporal end differentiated between the cognitively impaired rats and normal rats (AUC 0.72, 95% confidence interval 0.55-0.84). Neither single nor multiparametric approaches could identify the rats that would develop post-traumatic epilepsy. Multiparametric MRI analysis of the hippocampus can be used to identify cognitive impairment after an experimental traumatic brain injury. This information can be used to select subjects for preclinical trials of cognition-improving interventions.
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