Authors :
Presenting Author: Teresa Ravizza, PhD – Mario Negri Institute for Pharmacological Research IRCCS
Ilaria Lisi, PhD student – Mario Negri Institute for Pharmacological Research IRCCS
Rossella Di Sapia, PhD – Mario Negri Institute for Pharmacological Research IRCCS
Annamaria Vezzani, PhD – Mario Negri Institute for Pharmacological Research IRCCS
Federico Moro, PhD – Mario Negri Institute for Pharmacological Research IRCCS
Elisa R Zanier, MD – Mario Negri Institute for Pharmacological Research IRCCS
Rationale:
Post-traumatic epilepsy (PTE) is a serious and currently untreatable consequence of traumatic brain injury (TBI). While reactive astrogliosis is a well-established pathological hallmark of both TBI and epilepsy, its specific contribution to PTE pathogenesis remains unclear. Using a well characterized mouse model of TBI associated with ~50% PTE incidence, we investigated functional and morphological changes in forebrain astrocytes before and after PTE onset using in vivo MRI and post-mortem immunohistochemical analyses. Methods:
Two distinct cohorts of mice were used. In the first cohort, adult CD1 male mice underwent sham surgery (n=15) or TBI (n=30) by controlled cortical impact (CCI). Longitudinal in vivo proton magnetic resonance spectroscopy (1H-MRS) was performed in the thalamus ipsilateral to the injured cortex before (3 weeks, w) and after (3 months, m) PTE onset. At 5 m, diffusion tensor imaging (DTI) and 3D structural MRI was done. Then, mice were ECoG-monitored to assess PTE development, and sacrificed for astrocyte-based histopathology. In the second cohort, TBI mice (n=21) were ECoG-monitored during the first week after CCI and stratified as high- or low-risk to develop PTE based on a previously validated ECoG signature (i.e., daily number of spikes/sharp waves in the contralateral hemisphere). TBI and sham mice (n=5) were then sacrificed at 3w for GFAP expression analysis.
Results:
TBI induced alterations in astrocytic metabolism as shown by a significant increase of myo-inositol and glutamate+glutamine in the ipsilateral thalamus at 3 w (p< 0.05 vs sham), as assessed by