The Anti-epilepttc And Brain Protective Role Of Low-dose Dexamethasone Pretreatment In Temporal Lobe Epilepsy

Objective: To investigate the anti-epileptic and brain protective mechanisms of low-dosedexamethasone (DEX) in temporal lobe epilepsy (TLE) in male rats, attempt to providereliable evidences for the treatment of TLE using some kinds of medicines correlated withglucocorticoids (GCs).Methods: Male Wister rats were continuously conducted water maze training for fivedays. The rats whose average escape latency of water maze was less than10s on the last dayof training were recruited in the further experiment. These rats were then randomly dividedinto sham group, KA kindled epilepsy group pretreated with normal saline (KA group),pretreated with low-dose DEX (DEX group), pretreated with mifepristone (MIFE group) orwith spironolactone (SPIRO group), respectively. Each group was divided into two subgroupsaccording to different time point after KA kindling for14d and21d, respectively. Eachsubgroup was composed of6rats, including control group with the same size. The refractorytemporal lobe epileptic model was established by KA microinjected into right Nucleusamygdalae of rats. The effects of these medicines on the EEG in temporal epileptic male ratswere observed successively for3hours after KA injection. Morris water maze was performedon the14d and21d after KA injection or sham operation, respectively. Moreover, after watermaze detection, rats were decapitated and brain samples were made for ultrastructural observation onCA1region in hippocampus.Results：1. Partial seizures and epileptic episodes more than IV level present after KAinjection in amygdala in rats, even occurred with status epilepticus. The kindling rate of themodel was90.6%. Typical epileptic seizures were not observed in Sham group.2. Parietalcortex EEG: The latency of epileptic discharge was prolonged in DEX group compared withthat of KA group and SPIRO group (P<0.05). The duration of seizure discharge within3hafter KA injection was decreased in DEX group and MIFE group than that of KA group andSPIRO group, respectively (P<0.05). The average amplitudes in KA group and SPIRO groupwere significantly increased than that of MIFE group (P<0.05).3. Morris water maze:Compared to Sham group, the average escape latency was significantly increased in that ofKA group, DEX group, MIFE group and SPIRO group after KA injected for14d or21d, respectively (P<0.05). The central zone was decreased in these groups (P<0.05), the swimmingpathway was lengthened (P<0.05) and the initial angle was enhanced (P<0.05). The averageescape latency of DEX group and SPIRO group was decreased compared to that of KA groupand MIFE group after KA kindling for14d and21d, respectively (P<0.05). Except for Shamgroup, there were no distinct differences of the central zone between other groups (P>0.05). InDEX group and SPIRO group, the swimming pathways were shortened compared to the KAgroup and MIFE group, respectively (P<0.05). The initial angles of DEX group and SPIROgroup were reduced compared with KA group and MIFE group after KA Kindled for21d(P<0.05).4. Ultrastructural observation of CA1region in hippocampus: Neuronal ultrastructure inSham group was nearly normal. The neurons apparently damaged present in KA group andMIFE group, and neuronal empty cytoplasm, mitochondria swelling and unclear synapticstructures were observed. The neuronal ultrastructure of DEX group and SPIRO group wererelatively slightly damaged.Conclusion：1. There is neuronal protective role of low-dose DEX short-termpretreatment in hippocampus in TLE male rats.2. Low-dose DEX may inhibit TLE via MRactivating.3. Low-dose DEX may protect hippocampal neurons and improve spatial memoryability in TLE via GR pathway.