Rationale: Experiments in rodent models show that traumatic brain injury (TBI) is often associated with blood-brain barrier dysfunction (BBBD) which induces TGF-beta signalling and epileptogenesis. Recordings from electrocorticography in rodents and encephalography in humans have shown abnormal periodic cortical network slowing in epilepsy, termed paroxysmal slow wave events (PSWE). The goal of the present study was to determine if early imaging of BBBD predicts PSWEs and if TGF-beta blockers reduce TBI-induced BBBD and PSWEs. Method: Using a model of repetitive mild TBI (rmTBI), rats were administered five impacts over five days. Rats were treated with either a specific (IPW, 20 mg/kg) or non-specific, FDA approved (losartan, 60mg/kg) TGF-beta antagonist, or saline following the first impact. BBBD was assessed blindly using contrast-enhanced MRI one week post-impact. PSWEs and seizures were monitored using electrocorticographic recordings conducted six months post-impact for four weeks. Results: Recordings from rmTBI animals documented an average of 347 and 12 PSWEs/day in rmTBI and sham controls, respectively (p < 0.001). PSWEs were more common than seizures. The extent of BBBD one week post-impact was not predictive of the occurrence of PSWEs. IPW, but not losartan, reduces the extent of BBBD following rmTBI. Conclusions: BBBD is common one week post-impact in a rat model of rmTBI. Abnormal brain activity, including PSWEs and spontaneous seizures indicate long-term neural dysfunction. PSWEs may serve as a new biomarker for delayed neuropathology following brain injury.
|Title of host publication||2019 CLAE Scientific MeetingAt: Winnipeg, Manitoba|
|State||Published - 20 Sep 2019|