Authors :
Presenting Author: Sreevidhya Ramakrishnan, PhD – Texas A&M University College of Medicine
Yue Li, MD – Texas A&M University Health Science Center
Ursula Winzer-Serhan, PhD – Texas A&M University Health Science Center
Samba Reddy, PhD, RPh – Texas A&M University Health Science Center
Rationale:
Post-traumatic epilepsy (PTE) is a chronic seizure disorder that develops after traumatic brain injury (TBI). Currently, there are few proven therapeutic interventions for disease modification of PTE development. Nicotinic α7-subtype receptors (nAChRs) may play a role in epileptogenesis. In this study, we evaluated the effect of PNU-120596, a positive allosteric modulator of α7 nAChRs, on seizures and neurological comorbidities in a PTE model.
Methods:
TBI was induced in mice with controlled cortical impact (CCI). PNU-120596 or vehicle was given daily for 21 days. Video-EEG was used to monitor for spontaneous recurrent seizures (SRS) and other electrographic biomarkers. Long-term neurological comorbidities, including sensorimotor function, memory, and depression, were assessed up to 4 months post-TBI.
Results:
Mice developed chronic PTE with robust SRS, epileptiform discharges within 40 days after TBI. They displayed marked cognitive and behavioral deficits. PNU-120596 significantly reduced the overall seizure burden and frequency of discharges with a modest change in the incidence of PTE development. However, PNU-120596 significantly improved motor coordination, cognitive function, and alleviated depression-like phenotypes in PTE mice. Conclusions: These findings demonstrate the therapeutic potential of targeting α7 nAChRs for modifying the PTE development and mitigating the TBI-associated comorbidities. Further studies are needed to ascertain the potential role of nicotinic α7 nAChRs in PTE development and neuropsychiatric comorbidities.
Funding:
This research was funded by the TAMU ADM grant.