Effects Of Sodium Valproate On The Excitability Of Neurons In The Medial Parabrachial Nucleus In Epileptic Mice Induced By Pilocarpine

Objective: Epilepsy is one of the common serious brain diseases,which often co-occur with sleep disorders,and their interaction may aggravate epilepsy progress.Temporal lobe epilepsy is a common refractory epilepsy,which tends to be accompanied by sleep disorders.Moreover,the medial parabrachial nucleus is a key brain structure of sleep phase transition.It is well known that the traditional antiepileptic drug(AED)sodium valproate can ameliorate sleep disorders in epileptic patients,but the mechanism is still unclear.In this study,temporal lobe epilepsy was associated with medial parbrachial nucleus,Whether sodium valproate can improve epileptic sleep disorder by regulating the excitability of medial parbrachial nucleus neurons was discussed.Methods: The pilocarpine(POLI)mice model of temporal lobe epilepsy was established.Twenty-eight days later,the mice were randomly divided into chronic epilepsy group(EP28d),sodium valproate intervention group(EP28d + VPA)and normal control group(Con).The whole cell patch clamp was used to record the excitability of the neurons in the medial parabrachial nucleus of the mice in each group.The Cox expression was detected by immunohistochemistry,and the Fos B expression was detected by immunofluorescence staining and Western blotting.Moreover,the subcellular localization and expression of GFAP protein,a marker of reactive astrocytosis related to epilepsy,were detected.Results: 1.The PILO-TLE model was successfully established in 63% mice in this study.The mortality was 31%,and 6% mice were failure to build the TLE model due to non seizure induced.2.Compared with the Con group,the action potential(AP)number of EP28 d group was increased significantly in medial parabrachial nucleus neurons(P < 0.05),the action potential threshold become decreased(P < 0.05);Compared with EP28 d group,the AP of EP28d+VPA group was decreased significantly(P < 0.05),the action potential threshold become increased(P < 0.05).3.The expression of Cox in EP28 d group was significantly higher than that of EP28 d group(P < 0.05).4.In the EP28 d group,GFAP positive area and Fos B positive cells were significantly increased than that of the Ctrl group(P < 0.05),while in the EP28d+VPA group,GFAP positive area and Fos B positive cells were significantly decreased than that of the EP28 d group(P < 0.05).5.The ptotein level of GFAP and Fos B in EP28 d group and EP28d+VPA group was significantly higher than that of the Con group(P<0.05),however,these protien of the EP28d+VPA group was significantly lower than that that of the EP28 d group(P < 0.05).Conclusions: 1.The excitability of neurons in the medial parabrachial nucleus was sinificantly increased in the chronic phase of TLE,accompanied by the increasing of reactive proliferation of astrocytes.Sodium valproate can reduce the neuronal excitability and the reactive proliferation of astrocytes in the medial parabrachial nucleus in mice in the chronic phase of TLE.2.Sodium valproate may improve sleep disorders in temporal lobe chronic epilepsy mice by affecting excitability of medial para-brachial nuclear neurons.