Indexed on: 19 Jul '18Published on: 19 Jul '18Published in: Journal of neurotrauma
Diagnosis of ongoing epileptogenesis and associated hyperexcitability after brain injury is a major challenge. As increased neuronal activity in the brain triggers a blood oxygenation level-dependent (BOLD) response in functional magnetic resonance imaging (fMRI), we hypothesized that fMRI could be used to identify the brain area(s) with hyperexcitability during post-injury epileptogenesis. We applied fMRI to detect the onset and spread of BOLD activation after pentylenetetrazol (PTZ)-induced seizures (PTZ, 30 mg/kg, i.p.) in 16 adult male rats at 2 months after lateral fluid-percussion (FPI)-induced traumatic brain injury (TBI). In sham-operated controls, the onset of the PTZ-induced BOLD response was bilateral and first appeared in the cortex. After TBI, 5 of 9 (56%) rats exhibited ipsilateral perilesional cortical BOLD activation, followed by activation of the contralateral cortex. In 4 of 9 (44%) rats, the onset of the BOLD response was bilateral. Interestingly, the latency from the PTZ injection to the onset of the BOLD response increased in the following order: sham-operated controls (ipsilateral 132 ±57 s, contralateral 132 ±57 s; p>0.05) < TBI with bilateral BOLD onset (ipsilateral 176 ± 54 s, contralateral 178 ± 52 s; p>0.05) < TBI with ipsilateral BOLD onset (ipsilateral 406 ± 178 s, contralateral 509 ± 140 s; p<0.05). Cortical lesion area did not differ between rats with ipsilateral vs. bilateral BOLD onset (p>0.05). In the group of rats with ipsilateral onset of PTZ-induced BOLD activation, none of the rats showed a robust bilateral thalamic BOLD response, only 1 of 5 rats had robust ipsilateral thalamic calcifications, and 4 of 5 rats had perilesional astrocytosis. These findings suggest the evolution of the epileptogenic zone in the perilesional cortex after TBI, which is sensitive to PTZ-induced hyperexcitability. Further studies are warranted to explore the evolution of thalamo-cortical pathology as a driver of epileptogenesis after lateral FPI.