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目的：症狀性癲癇通常是由大腦損傷引起的，但大多數人患有這種腦損傷的人不會進而發展為癲癇，這表明，有些人擁有癲癇的易感基因。全基因組關聯研究（GWAS）是一種找到複雜疾病潛在基因的有效方法。最近關於對中國人口症狀性癲癇的GWAS報導了一個在1q32.1的CAMSAP1L1基因 (也叫做CAMSAP2) 上最顯著的單核苷酸多態性rs2292096 [G] （p=1.0×10⁻⁸，OR=0.63）。除了這個SNP，我們還選擇另一個在ERBB4基因上的潛在SNP rs13021324 [C]（p=5.8×10⁻⁵，OR=0.73）作為我們的研究。 CAMSAP1L1編碼一種細胞骨架蛋白，但是，它是否具有任何神經特定功能尚未知曉。 ERBB4是一個精神分裂症的易感基因，也有文章報導了ERBB4的突變引起了早期肌陣攣性腦病。我們推測，這兩個基因會影響人發展成為症狀性癲癇的易感性，以上的單核苷酸多態性會影響基因的表達或功能。這項研究的目標是，探索CAMSAP1L1的一些功能，和比較基因型之間以及癲癇患者和對照組之間這兩個基因的表達。 / 方法：在癲癇患者樣品中，我們對CAMSAP1L1 的SNP（rs2292096）和ERBB4的SNP（rs13021324）進行基因分型，首先將從癲癇患者的冰凍組織中提取RNA和蛋白質，他們的表達水平將分別通過實時PCR和蛋白印跡來測量，看家基因GAPDH用於測量對照，然後將不同的單核苷酸多態性與相應的表達水平關聯來觀察單核苷酸多態性是否會影響表達水平。同時，我們收集了匹配的癲癇患者和普通人的海馬和顳葉的石蠟包埋樣品，我們將通過免疫組化來測量樣品之間CAMSAP1L1這種蛋白表達水平是否不同。此外，對於基因CAMSAP1L1，我們將使用SH-SY5Y細胞進行雙螢光實驗，嘗試看到它在細胞中的位置，同時通過轉染來研究它對於神經突增長的一些功能。 / 結果：在顳葉有關SNP rs2292096（CAMSAP1L1）的RNA表達相關分析中，GG基因型患者呈現出高表達的趨勢（p=0.024）。而在相同的蛋白關聯分析中，則沒有看到這種趨勢（p=0.568）。在免疫組化試驗中，海馬部位的CASMAP1L1對照組的表達有高於癲癇組的趨勢（p=0.059）。而在顳葉，這兩組中觀察到的差異很小（p=0.12）。 在rs13021324（ERBB4）在RNA關聯表達分析中，攜帶等位基因C的患者的表達有高於T等位基因的一些趨勢, 但是不是很明顯。雙螢光試驗中，我們看到CAMSAP1L1在神經突的表達，它與β-微管蛋白有部分的表達重疊，在CAMSAP1L1轉染實驗中，近60的基因被抑制，在0μM和25μM RA 分化的SH-SY5Y細胞中，CAMSAP1L1的siRNA引起的基因沉默顯著增強了神經突以及分支的生長。 / 結論：在GWAS中發現的CAMSAP1L1基因上SNP的 顯著型p值表明，SNP和癲癇之間的遺傳性關聯可能是由於特定SNP標記的單體型的蛋白質表達水平和功能所決定的。我們的數據表明，在SNP rs2292096中，GG基因型的人倾向于有較高的表達，但需要更多的實驗來證實這一結果。CAMSAP1L1會抑制神經突生長。對於基因ERBB4，在C等位基因型中輕微高ErbB4的表達和我們的GWAS以及和以前的研究相符。 / Purpose: Symptomatic epilepsy is initiated by a brain insult, but most people suffering brain insults do not go on to develop epilepsy, indicating that some people are genetically predisposed to epilepsy after such insults. Genome wide association study (GWAS) is an effective way to find genes that contribute to diseases. The most significant SNP in a recent GWAS of symptomatic epilepsy in the Chinese population was rs2292096 [G] (p=1.0×10⁻⁸, OR=0.63), in the CAMSAP1L1 gene, also known as CAMSAP2. We chose to study this SNP as well as another SNP associated with epilepsy in the same GWAS, rs13021324 [C] (p=5.8×10⁻⁵, OR=0.73), which is in the epilepsy candidate gene ERBB4. CAMSAP1L1 encodes a cytoskeletal protein; however, it is not yet known to have any neurologically-specific function. ERBB4, a schizophrenia-susceptibility gene, has been reported to be mutated in a case of early myoclonic encephalopathy. We hypothesize that these two genes affect the predisposition of people to develop symptomatic epilepsy, and that the above SNPs influence gene expression or function. The objectives of this study are to elucidate some functions of CAMSAP1L1 and to explore whether the expression of the two genes will be affected by different genotypes. / Methods: One CAMSAP1L1 SNP (rs2292096) and one ERBB4 SNP (rs13021324) were genotyped in epilepsy patients. RNA and homogenates were prepared from frozen hippocampus and temporal lobe tissue from epilepsy patients. CAMSAP1L1 and ERBB4 RNA and protein levels were measured by real-time PCR and western blotting with reference to the housekeeping gene GAPDH, and expression levels were compared among genotypes of the above SNPs. We performed immunohistochemistry in paraffin-embedded sections to compare CAMSAP1L1 protein levels between epilepsy and control subjects in hippocampus and temporal lobe. In addition, we used human SH-SY5Y neuroblastoma cells to examine CAMSAP1L1 localization and function, performing double immunofluorescence for CAMSAP1L1 and tubulin and measuring the effect of CAMSAP1L1 knockdown on neurite outgrowth. / Results: In analysis of rs2292096 (CAMSAP1L1) in the temporal lobe, patients with the GG genotype showed higher expression of RNA (p=0.024), but not of protein (p=0.57). Immunohistochemistry showed a tendency toward lower expression of CAMSAP1L1 in epilepsy patients than in control subjects (p=0.059) in hippocampus but not in temporal lobe (p=0.12). Expression analysis of rs13021324 demonstrated non-significant tendencies toward higher expression of ErbB4 with C allele than the T allele for RNA and protein in hippocampus and temporal lobe. Double immunofluorescence showed CAMSAP1L1 expression on neurites, partially overlapping with β-tubulin. CAMSAP1L1 siRNA transfection of SH-SY5Y cells treated with or without retinoic acid reduced the CAMSAP1L1 protein level nearly 60% and stimulated neurite outgrowth, as measured by outgrowths, processes and branches compared with the control siRNA group. / Conclusion: The association of CAMSAP1L1 and ERBB4 SNPs with epilepsy is likely due to linkage disequilibrium with SNPs that affect functions or levels of CAMSAP1L1 or ErbB4. Our data suggest that the rs2292096 GG genotype, which reduces risk of symptomatic epilepsy, tends to increase expression of CAMSAP1L1, but more subjects are needed to confirm this result. CAMSAP1L1 represses neurite outgrowth. A tendency toward higher expression of ErbB4 with the C allele is consistent with the GWAS finding that the C allele decreases risk and with a report that ErbB4 levels are decreased in epilepsy. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zhang, Shuai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 77-94). / Abstracts also in Chinese. / Abstract --- p.I / 摘要 --- p.III / Acknowledgements --- p.V / List of figures --- p.VI / List of tables --- p.VIII / List of abbreviations --- p.IX / Table of contents --- p.XII / Chapter Chapter One --- Introduction --- p.1 / Chapter 1.1 --- Introduction to epilepsy --- p.1 / Chapter 1.1.1 --- Epilepsy types and epidemiology --- p.1 / Chapter 1.1.2 --- Drug-resistant epilepsy --- p.2 / Chapter 1.1.3 --- Treatment for epilepsy --- p.3 / Chapter 1.2 --- Genetics of epilepsy --- p.5 / Chapter 1.2.1 --- Genetic mechanism underlying epilepsy --- p.5 / Chapter 1.2.2 --- Gene expression in epilepsy --- p.8 / Chapter 1.2.3 --- Genomics in epilepsy --- p.10 / Chapter 1.2.4 --- Animal models --- p.11 / Chapter 1.3 --- Methods to identify variants affecting disease susceptibility --- p.12 / Chapter 1.3.1 --- Traditional methods to identify genetic loci for disease susceptibility --- p.12 / Chapter 1.3.2 --- Genome wide association study (GWAS) --- p.12 / Chapter 1.3.3 --- A GWAS of symptomatic epilepsy in the Chinese population --- p.14 / Chapter 1.4 --- Functions of the CAMSAP family --- p.18 / Chapter 1.5 --- Functions of ErbB4 --- p.21 / Chapter 1.6 --- Hypothesis and proposed plan for expression study of CAMSAP1L1 and ERBB4 --- p.22 / Chapter 1.6.1 --- Proposed hypothesis of CAMSAP1L1 and ERBB4 in symptomatic epilepsy --- p.22 / Chapter 1.6.2 --- Objectives of the study --- p.22 / Chapter 1.6.3 --- Significance of the study --- p.23 / Chapter 1.7 --- Study scheme --- p.23 / Chapter Chapter Two --- RNA expression analysis of SNPs rs2292096 and rs13021324 --- p.24 / Chapter 2.1 --- Introduction --- p.24 / Chapter 2.2 --- Materials and methods --- p.24 / Chapter 2.2.1 --- Materials --- p.24 / Chapter 2.2.2 --- Genotyping --- p.25 / Chapter 2.2.3 --- RNA extraction --- p.26 / Chapter 2.2.4 --- Reverse transcription PCR --- p.27 / Chapter 2.2.5 --- Real-time PCR --- p.27 / Chapter 2.2.6 --- Data analysis --- p.29 / Chapter 2.3 --- Results and discussions --- p.29 / Chapter 2.3.1 --- Genotyping --- p.29 / Chapter 2.3.2 --- Real-time PCR --- p.31 / Chapter 2.4 --- Conclusion --- p.35 / Chapter Chapter Three --- Protein expression analysis of rs2292096 and rs13021324 --- p.37 / Chapter 3.1 --- Introduction --- p.37 / Chapter 3.2 --- Materials and methods --- p.37 / Chapter 3.2.1 --- Materials --- p.37 / Chapter 3.2.1 --- Protein extraction --- p.38 / Chapter 3.2.3 --- Western blot --- p.38 / Chapter 3.2.4 --- Western blot for quantification of protein samples --- p.39 / Chapter 3.3 --- Results and discussion --- p.40 / Chapter 3.3.1 --- CAMSAP1L1 band confirmation --- p.40 / Chapter 3.3.2 --- ErbB4 immunobloting --- p.43 / Chapter 3.4 --- Conclusion --- p.48 / Chapter Chapter Four --- Immunohistochemistry analysis of CAMSAP1L1 --- p.49 / Chapter 4.1 --- Introduction --- p.49 / Chapter 4.2 --- Materials and methods --- p.49 / Chapter 4.2.1 --- Materials --- p.49 / Chapter 4.2.2 --- Immunohistochemistry --- p.50 / Chapter 4.2.3 --- Quantification of FFPE samples by Image Pro-Plus --- p.51 / Chapter 4.3 --- Results and discussion --- p.52 / Chapter 4.3.1 --- CAMSAP1L1 immunohistochemistry --- p.52 / Chapter 4.3.2 --- CAMSAP1L1 protein quantification between epilepsy and control groups --- p.54 / Chapter 4.4 --- Conclusions --- p.57 / Chapter Chapter Five --- Double immunofluorescence and CAMSAP1L1 siRNA transfection in SH-SY5Y cells --- p.58 / Chapter 5.1 --- Introduction --- p.58 / Chapter 5.2 --- Materials and methods --- p.59 / Chapter 5.2.1 --- Materials --- p.59 / Chapter 5.2.2 --- Double immunofluorescence --- p.60 / Chapter 5.2.3 --- CAMSAP1L1 siRNA transfection --- p.60 / Chapter 5.2.4 --- Gene knockdown assay --- p.61 / Chapter 5.2.4 --- MTT cell viability assay --- p.62 / Chapter 5.2.5 --- Neurite outgrowth assay --- p.62 / Chapter 5.3 --- Results and discussion --- p.63 / Chapter 5.3.1 --- Double immunofluorescence --- p.64 / Chapter 5.3.2 --- CAMSAP1L1 knockdown assay by western blot --- p.64 / Chapter 5.3.3 --- MTT cell viability assay --- p.66 / Chapter 5.3.4 --- Neurite outgrowth --- p.67 / Chapter 5.4 --- Conclusion --- p.72 / Chapter Chapter Six --- Overall conclusion and prospects --- p.73 / Chapter 6.1 --- Overall conclusion --- p.73 / Chapter 6.1.1 --- CAMSAP1L1 --- p.73 / Chapter 6.1.2 --- ErbB4 --- p.74 / Chapter 6.2 --- Future work --- p.74 / Chapter 6.3 --- Prospects --- p.75 / References --- p.77

This dissertation presents the system architecture and implementation of two wireless systems-on-chip (SoCs) for diagnostics and treatment of neurological disorders. It also validates the SoCs as an electronic implant for preoperative monitoring and treatment of intractable epilepsy. The first prototype SoC is a neural recording interface intended for wireless monitoring of intractable epilepsy. The 0.13um CMOS SoC has 64 recording channels, 64 programmable FIR filters and an integrated 915MHz FSK PLL-based wireless transmitter. Each channel contains a low-noise amplifier and a modified 8-bit SAR ADC that and can provide analog-digital multiplication by modifying the ADC sampling phase. It is used in conjunction with 12-bit digital adders and registers to implement 64 16-tap FIR filters with a minimal area and power overhead. In vivo measurement results from freely moving rodents demonstrate its utility in preoperative monitoring epileptic seizures. Treatment of intractable epilepsy by responsive neurostimulation requires seizure detection capabilities. Next, a low-power VLSI processor architecture for early seizure detection is described. It the magnitude, phase and phase synchronization of two neural signals - all precursors of a seizure. The processor is utilized in an implantable responsive neural stimulator application. The architecture uses three CORDIC processing cores that require shift-and-add operations but no multiplication. The efficacy of the processor in epileptic seizure detection is validated on human EEG data and yields comparable performance to software-based algorithms. The second prototype SoC is a closed-loop 64-channel neural stimulator that includes the aforementioned seizure detector processor and is used for preventive seizure abortion. It constitutes a neural vector analyzer that monitors the magnitude, phase and phase synchronization of neural signals to enable seizure detection. In a closed loop, abnormal phase synchrony triggers the programmable-waveform biphasic neural stimulator. To implement these functionalities, the 0.13um CMOS SoC integrates 64 amplifiers with switched-capacitor (SC) bandpass filters, 64 MADCs, 64 16-tap FIR filters, a processor, 64 biphasic stimulators and a wireless transmitter. The SoC is validated in the detection and abortion of seizures in freely moving rodents on-line and in early seizure detection in humans off-line. The results demonstrate its utility in treatment of intractable epilepsy.

This dissertation presents the system architecture and implementation of two wireless systems-on-chip (SoCs) for diagnostics and treatment of neurological disorders. It also validates the SoCs as an electronic implant for preoperative monitoring and treatment of intractable epilepsy. The first prototype SoC is a neural recording interface intended for wireless monitoring of intractable epilepsy. The 0.13um CMOS SoC has 64 recording channels, 64 programmable FIR filters and an integrated 915MHz FSK PLL-based wireless transmitter. Each channel contains a low-noise amplifier and a modified 8-bit SAR ADC that and can provide analog-digital multiplication by modifying the ADC sampling phase. It is used in conjunction with 12-bit digital adders and registers to implement 64 16-tap FIR filters with a minimal area and power overhead. In vivo measurement results from freely moving rodents demonstrate its utility in preoperative monitoring epileptic seizures. Treatment of intractable epilepsy by responsive neurostimulation requires seizure detection capabilities. Next, a low-power VLSI processor architecture for early seizure detection is described. It the magnitude, phase and phase synchronization of two neural signals - all precursors of a seizure. The processor is utilized in an implantable responsive neural stimulator application. The architecture uses three CORDIC processing cores that require shift-and-add operations but no multiplication. The efficacy of the processor in epileptic seizure detection is validated on human EEG data and yields comparable performance to software-based algorithms. The second prototype SoC is a closed-loop 64-channel neural stimulator that includes the aforementioned seizure detector processor and is used for preventive seizure abortion. It constitutes a neural vector analyzer that monitors the magnitude, phase and phase synchronization of neural signals to enable seizure detection. In a closed loop, abnormal phase synchrony triggers the programmable-waveform biphasic neural stimulator. To implement these functionalities, the 0.13um CMOS SoC integrates 64 amplifiers with switched-capacitor (SC) bandpass filters, 64 MADCs, 64 16-tap FIR filters, a processor, 64 biphasic stimulators and a wireless transmitter. The SoC is validated in the detection and abortion of seizures in freely moving rodents on-line and in early seizure detection in humans off-line. The results demonstrate its utility in treatment of intractable epilepsy.

Submitted in fulfilment of the requirements for the Degree in Masters of Technology: Nursing, Durban University of Technology, 2013. / Epilepsy is one of the world’s most common neurological disorders of the brain. It is a condition that affects individuals in most countries worldwide. However, there is still stigma attached to epilepsy, and the condition is often misunderstood. However, there are people who understand the condition and the care that PWE need. Aim of the study : The aim of the study was to describe the lived experiences of people with epilepsy. Methodology : A descriptive phenomenological methodology was used. This study is guided by Parse’s Theory of Human Becoming. In-depth interviews were conducted with eight participants. The main research question that was asked in this study was: What are experiences of people living with epilepsy? Results : The findings of this study revealed that people with epilepsy still face challenges unique to their lifestyles. The lack of knowledge among communities has led to negative experiences of people with epilepsy. Family members often provide support to people with epilepsy; especially female partners support their husbands.

The aim of this study is to isolate and evaluate the anticonvulsant components from the leaves of Leonotis leonorus (L) R.aR. and to see if there is any change in activity with the origin of the plant material and I or the season in which plant material is collected. Therefore, in this study, two sites were chosen for collection of plant material and the collection was made in summer and in winter. Chemical, physical and pharmacological methods were used to isolate, identify and to evaluate compounds isolated from the leaves of Leonotis leonorus for anticonvulsant activity.

The aim of this study is to isolate and evaluate the anticonvulsant components from the leaves of Leonotis leonorus (L) R.aR. and to see if there is any change in activity with the origin of the plant material and I or the season in which plant material is collected. Therefore, in this study, two sites were chosen for collection of plant material and the collection was made in summer and in winter. Chemical, physical and pharmacological methods were used to isolate, identify and to evaluate compounds isolated from the leaves of Leonotis leonorus for anticonvulsant activity.

A epilepsia é uma patologia que afeta 50 milhões de pessoas, sendo que cerca de 30% dos pacientes apresentam epilepsia refratária, ou seja, não respondem a terapia medicamentosa disponível. Portanto, é necessária a busca contínua de novos fármacos. Os complexos organometálicos vêm ao encontro a esta necessidade conjugando moléculas já aplicadas na terapia (como o ácido valproico), a metais essenciais e outros ligantes a fim de aprimorar os efeitos farmacológicos. Neste trabalho foram testados quatro complexos derivados do ácido valproico: [Cu(Valp)2Fen] , [Cu(Valp)2Bipi], [Zn(Valp)2Fen] e [Zn(Valp)2Bipi], através do screening toxicológico embrionário e atividade anticonvulsivante em zebrafish induzidos por pentilenotetrazol (PTZ). O complexo [Cu(Valp)2Bipi] apresentou maior toxicidade embrionária (CL50=0.12 μM), seguido pelo [Zn(Valp)2Bipi] (CL50 = 10μM). Estes mesmo complexos nas doses de 10 mM/Kg, 30 mM/Kg e 100 mM/Kg para derivado contendo zinco a intensidade das convulsões em relação ao valproato de sódio (175 mM/Kg) em peixes adultos, demonstrando ação superior ao fármaco tradicional. Devido a baixa toxicidade aliada a ação anticonvulsivante evidente selecionamos o derivado [Zn(Valp)2Bipi] para estudos futuros em modelos complexos de epilepsia. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2016-04-29T13:43:16Z No. of bitstreams: 1 Dissertacao Lauren Dockhorn Grunspan.pdf: 2281256 bytes, checksum: 5ed8d708e6f55d2418086df48fc4f6ac (MD5) / Made available in DSpace on 2016-04-29T13:43:16Z (GMT). No. of bitstreams: 1 Dissertacao Lauren Dockhorn Grunspan.pdf: 2281256 bytes, checksum: 5ed8d708e6f55d2418086df48fc4f6ac (MD5) Previous issue date: 2016-04-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES / The most important determinant of quality of life in patients with epilepsy is complete seizure control, and therefore this should be the ultimate goal of pharmacological therapy. Unfortunately, around 30% of epileptic patients still suffer with refractory epilepsy. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and the research. In this study, we access the embryo toxicity and anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, derivative with valproic acid and the N-donor ligand in adult zebrafish pentylenetetrazole epileptic seizure model. [Cu(Valp)2Bipy] LC50 in 48 Hours Post Fertilization (hpf) was 0.22 μM and 0.12 μM in 96 hpf followed by [Zn(Valp)2Bipy] (LC50 = 10 μM). This same metallodrugs ([CuValp)2Bipi] 10 mM/Kg and [Zn(Valp)2Bipi] 30 mM and 100 mM/Kg) displayed a superior activity reducing the seizure intensity compared to Sodium Valproate (175 mM/Kg). As conclusion, among all, the [Cu(Valp)2Bipi] showed the best anticonvulsant effects, but due to its toxic effects on embryos and larvae, the [Zn(Valp)2Bipi] should be considered the most promising for future studies as anticonvulsant drug.

A epilepsia é uma patologia que afeta 50 milhões de pessoas, sendo que cerca de 30% dos pacientes apresentam epilepsia refratária, ou seja, não respondem a terapia medicamentosa disponível. Portanto, é necessária a busca contínua de novos fármacos. Os complexos organometálicos vêm ao encontro a esta necessidade conjugando moléculas já aplicadas na terapia (como o ácido valproico), a metais essenciais e outros ligantes a fim de aprimorar os efeitos farmacológicos. Neste trabalho foram testados quatro complexos derivados do ácido valproico: [Cu(Valp)2Fen] , [Cu(Valp)2Bipi], [Zn(Valp)2Fen] e [Zn(Valp)2Bipi], através do screening toxicológico embrionário e atividade anticonvulsivante em zebrafish induzidos por pentilenotetrazol (PTZ). O complexo [Cu(Valp)2Bipi] apresentou maior toxicidade embrionária (CL50=0.12 μM), seguido pelo [Zn(Valp)2Bipi] (CL50 = 10μM). Estes mesmo complexos nas doses de 10 mM/Kg, 30 mM/Kg e 100 mM/Kg para derivado contendo zinco a intensidade das convulsões em relação ao valproato de sódio (175 mM/Kg) em peixes adultos, demonstrando ação superior ao fármaco tradicional. Devido a baixa toxicidade aliada a ação anticonvulsivante evidente selecionamos o derivado [Zn(Valp)2Bipi] para estudos futuros em modelos complexos de epilepsia. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES / The most important determinant of quality of life in patients with epilepsy is complete seizure control, and therefore this should be the ultimate goal of pharmacological therapy. Unfortunately, around 30% of epileptic patients still suffer with refractory epilepsy. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and the research. In this study, we access the embryo toxicity and anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, derivative with valproic acid and the N-donor ligand in adult zebrafish pentylenetetrazole epileptic seizure model. [Cu(Valp)2Bipy] LC50 in 48 Hours Post Fertilization (hpf) was 0.22 μM and 0.12 μM in 96 hpf followed by [Zn(Valp)2Bipy] (LC50 = 10 μM). This same metallodrugs ([CuValp)2Bipi] 10 mM/Kg and [Zn(Valp)2Bipi] 30 mM and 100 mM/Kg) displayed a superior activity reducing the seizure intensity compared to Sodium Valproate (175 mM/Kg). As conclusion, among all, the [Cu(Valp)2Bipi] showed the best anticonvulsant effects, but due to its toxic effects on embryos and larvae, the [Zn(Valp)2Bipi] should be considered the most promising for future studies as anticonvulsant drug.