Abstracts

Rationale: The hippocampus of subjects with severe traumatic brain injury (TBI) is susceptible to present neuronal death and post-traumatic hyperexcitability. At present, there are no drugs that prevent these alterations. Previous studies from our group indicate that the administration of propylparaben (PPB) induces hippocampal neuroprotective effects short- and long-term after pilocarpine-induced status epilepticus. Therefore, the aim of this study was to evaluate the effect of subchronic treatment with PPB on hippocampal damage induced by TBI. Methods: Forty-four male Wistar rats (250-300 g) were used and divided in four independent groups. The TBI-PPB (n=11) and TBI (n=11) groups were subjected to a severe TBI (lateral fluid percussion model) followed by daily administration of PPB (178 mg/kg, ip) or vehicle (polyethylene glycol (PEG) 30%, ip), respectively during 5 days. The PPB (n=11) and SHAM (n=11) groups received only the treatments (PPB or PEG) and handling, without trauma induction. According to the Neuroscore rate, animals with TBI presented severe neuromotor deficit. At day 23 post-TBI or manipulation, a bipolar electrode was implanted in the ipsilateral ventral hippocampus. One week after the surgery (30 days post-TBI), the afterdischarge threshold (ADT) was estimated to determine the hippocampal excitability. Subsequently, the animals were sacrificed and the brain used for evaluation of hippocampal volume (ex-vivo magnetic resonance imaging). Results: SHAM group presented an ADT of 299 ± 22.5 µA and hippocampal volume of 48.07 ± 4.08 mm3. In contrast to the SHAM group, PPB group showed no significant changes (ADT, 291.7 ± 21.58 µA and volume 45 ± 3.03 mm3). TBI group presented a significant reduction in ADT (64.2%, p<0.001) and hippocampal volume (15.31%, p<0.001) with respect to SHAM group. In contrast to the SHAM group, TBI-PPB group obtained no significant differences in the ADT estimation (249.5 ± 75.17 µA, p> 0.05), and a lesser reduction in the hippocampal volume (10.7%; p<0.05) when compared to TBI group. Conclusions: Subchronic post-TBI treatment with PPB reduces the long-term hyperexcitability and lessened the volume reduction of hippocampus induced by a severe TBI. These results reveal the PPB can represent a therapeutic strategy to reduce the consequences of TBI on hippocampal dysfunction. Funding: During the preparation of this project, financial support was provided by the National Council of Science and Technology (CONACyT) through the master's scholarship number 615621 and project 220365.