| Female sex hormone, progesterone, in addition to seizure modifying activity is also known as a potential protective agent against various brain injury conditions. Considering the predisposal role of traumatic brain injury
(TBI) on developing post-traumatic epilepsy (PTE), the effect of progesterone on post-traumatic epileptogenesis
is not investigated yet. Male Wistar rats were given a moderate focal weight drop injury (500 gr) or sham surgery
and then progesterone (16 and 32mg/kg) was given daily for two consecutive weeks. On day 15 of injury,
seizures were induced by administration of a GABAA receptor antagonist, pentylenetetrazole (PTZ, 30 mg/kg).
Seizures were then assessed over a 1-h period using the Racine clinical rating scale.
Traumatized animals that received 32 mg/kg progesterone had reduced score, duration of seizures and almost
did not show tonic-clonic seizures during 60 min versus the untreated trauma group. In line with behavioral
alterations, 32 mg/kg progesterone enhanced the amount of Nrf2 and HO-1 proteins and decreased the level of
NF-kB, BDNF, Caspase 3 and ratio of Bax/Bcl-2 in the ipsilateral hippocampus. Additionally, the number of
TUNEL-positive apoptotic cells, as well as injured dark neurons in the parietal cortex and hippocampal CA1 of
32 mg/kg-treated animals showed a significant reduction. Administration of 16 mg/kg progesterone elevated
production of BDNF, Bax and Caspase 3 and decreased anti-apoptotic Bcl-2 protein. Taken together, an early
administration of 32 mg/kg of progesterone after TBI for two weeks post-injury modified seizure activity.
Our findings suggest that post-traumatic anti-epileptogenesis property of a high dose of progesterone partly
occurs through the manipulation of BDNF-TrkB axis along with control of cell survival pathways. |