Progress in pharmacogenomics and efficacy prediction of levetiracetam / 中华神经科杂志

Levetiracetam (LEV) is the second generation of broad-spectrum antiepileptic drugs. Compared with other antiepileptic drugs, LEV has unique antiepileptic mechanism, good efficacy and tolerance, and its target is synaptic vesicle protein 2A. With the widespread use of LEV, more and more adverse reactions have been reported, especially mental related adverse reactions. This paper reviewed the research progress of LEV pharmacogenomics related targets, metabolism, adverse reaction related genetic variation and efficacy prediction, so as to provide decision-making for the application of LEV individualized treatment in clinical practice, improve the quality of life of epileptic patients and reduce the disease burden of patients with epilepsy.

Recent advance in roles of brain-derived neurotrophic factor-tyrosine receptor kinase B signaling pathway genes and their encoded proteins in epilepsy / 中华神经医学杂志

Brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) signaling pathway may play important roles in a variety of neurological diseases, particularly in the development and treatment of epilepsy. The BDNF gene and NTRK2 gene are genes encoding BDNF and TrkB proteins in this pathway. The variations in these two genes may affect the occurrence and treatment of epilepsy through leading to abnormal functions and expressions of the encoded proteins, which may affect the degrees of activation of BDNF-TrkB signaling pathway. This article summarizes the pathophysiological processes of epilepsy in which BDNF-TrkB signaling pathway genes and their encoded proteins may be involved.

Regulation of transcription factors in astrocyte-to-neuron transdifferentiation / 中华神经医学杂志

More and more researches demonstrate that astrocytes display the markers of neural stem cells or progenitor cells and have the potential of neural differentiation.Thus,it is possible that astrocytes,especially overactive astrocytes,could replace injured neurons and repair the damaged function by transdifferenting and gene reprogramming.Here,we summarize recent progresses of various transcription factors and their regulation in astrocytes-to-neurons transdifferentiation.

Influencing Factors Involved in the Progression of Epileptic Seizure at the Acute Phase of Encephalitis into Postencephalitic Epilepsy / 中风与神经疾病杂志

@#Objective To investigate the factors that affect the progression of epileptic seizure at the acute phase of encephalitis into postencephalitic epilepsy.Methods A retrospective analysis was conducted to investigate the clinical data of 141 patients who were admitted to the First People’s Hospital of Yunnan Province and the First Affiliated Hospital of Kunming Medical University from January 2010 to June 2019，diagnosed as autoimmune encephalitis or viral encephalitis in the acute phase with epileptic seizure and treated with immunotherapy. The 141 patients were divided into 2 groups according to whether their epileptic seizure progressed to postencephalitic epilepsy. Logistic regression analysis was applied to investigate the factors that affect the progression of epileptic seizure at the acute phase of encephalitis into postencephalitic epilepsy.Results The epileptic seizure of 25 patients（17.73% of all 141 patients） progressed to postencephalitic epilepsy. The results of multi-factor Logistic regression analysis show that the risk factors involved in the progression of epileptic seizure included：a fever before treatment（OR=3.288，95％CI=1.116～9.687，P=0.031） and high seizure frequency（≥10 times/day）（OR=4.564，95％CI=1.263～16.491，P=0.021）. Compared with a course of antiepileptic drugs for less than 6 months，a course of antiepileptic drugs for 6-12 months（OR=0.672，95％CI=0.064～7.024，P=0.740） or above（OR=3.049，95％CI=0.906～10.261，P=0.072） did not affect the development of postencephalitic epilepsy. Compared with the patients with no fever before treatment，those with fever were more prone to disturbance of consciousness（P<0.001），status epilepticus（P=0.023） and a head MRI showing inflammatory lesions（P=0.007）.Conclusion Therefore，a fever before treatment and high seizure frequency（≥10 times/day） are identified as the risk factors causing postencephalitic epilepsy. The length of course of antiepileptic drugs does not affect the incidence of postencephalitic epilepsy，suggesting that it is unnecessary to prevent postencephalitic epilepsy by long-term use of antiepileptic drugs.

Construction and identification of lentivirus-mediated vectors targeting CNN3 gene in the rat hippocampus / 中国比较医学杂志

Objective To establish a method focusing on regulation of CNN3 gene in the rat hippocampus and help to explore the role of CNN3 gene played in the brain physiology and pathology.Methods One cDNA sequence and three shRNAs targeting CNN3 gene were designed and synthesized.The recombinant lentivirus-mediated expressing and three short hairpin RNA ( shRNA) vectors targeting CNN3 gene in the rats were constructed with engineering technology.All recombinant vectors were intravenously injected into rats hippocampi guided by stereotaxic apparatus.Western blot was performed to explore the best shRNA and to study the changes of CNN3 gene in the rat hippocampus after transfection with the silence and over-expressed vectors.Results The lentivirus-mediated vector expressing CNN3-OE and three shRNA vectors targeting CNN3 gene were successfully constructed.Within eight weeks after transfection, the vectors of CNN3-OE and three CNN3-shRNAs changed the expression of CNN3 gene in the rat hippocampus, in particular, all the protein levels of calponin-3 encoded by CNN3 gene were significantly down-regulated along with the time, with the highest inhibitory rate of 73.6%in the CNN3-shRNA2 group.Significant up-regulation of calponin-3 protein level by 93.88%, was found only on the 14th day after transfection.Conclusions Lentivirus-mediated vectors of CNN3-OE and CNN3-shRNAs may regulate in vivo the CNN3 gene level in the local brain region of rats via stereotactic injection.The study lays a foundation for disease prevention and treatment in the future.