戊四氮致痫大鼠脑内热休克蛋白70的表达

目的：探讨热休克蛋白70（HSP70）在癫痫大鼠脑内的表达情况及其意义。方法：采用戊四氮致痫模型。应用免疫组织化学及常规清理检查的方法进行研究。结果：在正常大鼠脑内未见HSP70免疫反应（IR）阳性细胞,成四氮致痫12小时后脑内开始出现HSP70IR阳性细胞,24小对IR达高峰．3天后开始下降．7天后消失。HSP70主要在边缘系统（尤其是海马的CA1、CA3、CA4区）、大脑皮质（尤其是颞叶皮质,梨状皮质）等区域表达。同时常规病理检查发现,上述区域散在出现受损的异常神经元。结论：癫痫发作可诱导HSP70在大鼠脑内广泛表达。HSP70表达可作为神经元受损的一个早期指标。     

青霉素致痫大鼠脑内HSP70的表达

目的 探讨应激蛋白HSP70在癫痫大鼠脑组织中的表迭及其意义。方法 采用腹腔注射青霉素法复制大鼠癫痫模型，免疫组织化学方法检测大脑皮层、海马组织中HSP70表迭的变化。结果 (1)实验组大鼠给药后均有程度不同的癫痫行为发生；(2)对照组大鼠脑内未见HSP70阳性细胞，青霉素致痈后大鼠大脑皮层、海马出现HSP70阳性细胞。在海马的CA1、CA3、CA4区和颞叶皮质HSP70阳性细胞较为密集。结论 青霉素致痫大鼠脑内可见HSP70的广泛表达，提示HSP70蛋白在癫痫发生过程中可能对神经元具有保护作用。     

尼莫地平对癫痫大鼠学习记忆及海马超微结构的影响

目的探讨尼莫地平(nimodipin,NIM)对戊四氮(pentylenetetrazol,PTZ)点燃癫痫大鼠学习记忆能力及海马CA3区超微结构的影响。方法动物分为正常对照组、PTZ组和NIM PTZ组,采用PTZ慢性点燃癫痫模型,应用Morris水迷宫观察各组大鼠空间学习记忆能力,电镜观察海马CA3区突触界面结构,并对突触活性参数量化分析。结果PTZ点燃癫痫大鼠存在学习记忆能力下降,其海马CA3区突触后致密物显著变薄、突触小泡显著减少、突触间隙显著增宽(P<0.05);尼莫地平能改善癫痫大鼠学习记忆障碍,与PTZ组比较,突触后致密物增厚、突触小泡增多、突触间隙变窄(P<0.05)。结论PTZ点燃癫痫大鼠存在空间学习记忆受损,可能与突触界面参数改变有关;NIM可以改善癫痫大鼠突触超微结构,提高学习记忆能力。     

托吡酯对慢性癫(癎)大鼠海马碱性成纤维细胞生长因子表达的影响

目的研究托吡酯（TPM）对慢性癫痫大鼠海马碱性成纤维细胞生长因子（bFGF）表达的影响。方法制作戊四氮（PTZ）慢性癫痫点燃大鼠模型，分为PTZ组、TPM组及正常对照组，每组又以5d、10d、15d3个时间点各分为3小组。免疫组化法观察各组海马CAl、CA3区及齿状回bFGF表达，HE染色观察病理形态学改变。结果（1）行为学观察：PTZ组和TPM组在癫痫发作上无明显差别。（2）bFGF表达：①各组齿状回区bFGF表达：PTZ组和TPM组各时点表达不断增高，与正常对照组比较差异有统计学意义（均P〈0．01），尤以10d及15d时增高更明显，与5d时比较差异有统计学意义（均P〈0．05）。②各组CAl区bFGF表达：PTZ组各时点均有明显表达，且随时间延长而表达不断增高，各时点比较差异有统计学意义（均P〈0．01），与正常对照组比较差异有统计学意义（均P〈0．01）；TPM组在5d时与正常对照组比较差异有统计学意义（P〈0．01），而10d、15d时逐渐下降，接近正常对照组水平。③各组CA3区bFGF表达：5d时3组比较差异无统计学意义。但PTZ组和TPM组在10d时与正常对照组比较差异有统计学意义（P〈0．01），PTZ组在15d时和TPM组及正常对照组比较差异有统计学意义（均P〈0．01）。（3）病理形态学改变：PTZ组和TPM组的海马CAl、CA3区尤其是CAl区可见较多神经元发生变性和坏死，PTZ组更显著。结论PTZ点燃过程中海马bF-GF表达增高，尤其在CAl区，且随时间延长有表达不断增高的趋势。TPM可能通过减少海马神经元损伤而明显下调海马CAl、CA3区bFGF的表达。     

弥漫性轴索损伤后脑组织中c-fos与HSP70的表达

目的：鼠脑弥漫性轴索损伤（DAI）后c-foa mRNA和HSP70 mRNA的表达。方法：应用原位杂交技术探讨了鼠脑弥漫性轴索损伤后c-fos mRNA和HSP70mRNA的表达。结果：打击后10后钟时,皮层中即出现c-fos mRNA表达,2小时表达强度增加,6小时达高峰,24小时开始下降。海马、丘脑及脑干部位的c-fos mRNA表达方式与皮层相拟。打击后6小时,皮层与海马中开始出现HSP70mRNA的表达,24小时时表达强度增加,丘脑及脑干等部位未见HSP70 mRNA的表达。结论：（1）DAI后可出现脑组织中c-fos mRNA和HSP70mRNA的表达;（2）DAI后c-fos mRNA的表达早于HSP70mRNA;（3）c-fos mRNA于脑组织中的表达较为弥散,而HSP70mRNA的表达则局限于皮层和海马区;（4）c-fos mRNA和HSP70 mRNA在DAI后的表达,对神经细胞具有保护作用。     

脑室出血大鼠不同部位脑组织热休克蛋白70表达的差异

目的 观察实验性大鼠脑室出血后,不同部位脑组织热休克蛋白70（heat shock protein 70,HSP70）表达的差异。方法 18只成熟雄性SD大鼠随机均分为正常组、对照组和模型组,采用侧脑室注血法制备大鼠脑室出血动物模型,然后用酶联免疫吸附方法制作热休克蛋白70组织切片,在显微镜下直接计数阳性细胞;采用干湿重法计算脑含水量。结果 模型组大鼠脑组织HSP70阳性细胞数和含水量明显高于正常组和对照组（P分别为0.015和0.013）,而且HSP70阳性细胞主要分布于皮层和皮层下,室周也有表达。结论 大鼠脑室内出血可引起远隔部位的皮层和皮层下组织HSP70的高度表达。     

戊四氮诱发癫痫大鼠海马齿状回颗粒细胞树突发芽

目的利用化学点燃大鼠癫痫模型,观察癫痫发作后大鼠海马齿状回颗粒细胞树突的形态学变化,探讨癫痫敏感性形成机制。方法利用戊四氮（PTZ）制作化学点燃大鼠癫痫模型。采用点燃成功后3d、7d两个时间点,应用神经元高尔基染色法,在光镜下观察和定量分析大鼠海马齿状回颗粒细胞的树突改变。结果颗粒细胞的形态学参数（树突总长度、树突分支点数、树突野最大伸展距离和树突棘密度）在PTZ点燃后3d时均显著降低（P〈0.05）,而在PTZ点燃后7d时明显回升,并明显高于生理水平（P〈0.05）。结论在PTZ点燃大鼠癫痫发作后,颗粒细胞树突出现明显的可塑性改变,并在PTZ点燃后7d时出现发芽现象,这可能与癫痫敏感性的形成有关     

戊四氮点燃癫(癎)大鼠海马巢蛋白和骨形成蛋白-4的表达研究

目的观察巢蛋白(nestin)和骨形成蛋白4(BMP4)基因在戊四氮(PTZ)点燃癫大鼠海马中的表达,并探讨两者与癫发病机制的关系。方法将81只成年雄性SD大鼠随机分为实验组(n=54)和对照组(n=27)。实验组采用PTZ点燃癫大鼠,按点燃中的不同时相点,又随机分为9组。用免疫组化技术、地高辛标记特异性寡核苷酸探针原位杂交组织化学技术,观察海马nestin和BMP4表达的变化。结果nestin阳性细胞在PTZ注射后3d开始出现在齿状回、CA3区和CA1区,到7d达到高峰,以后逐渐减少。BMP4在PTZ注射后7d开始增多,在点燃后1d达到高峰,以后逐渐减少,主要分布在齿状回、CA3区和CA1区。结论PTZ点燃可引起海马内星形胶质细胞增生、活化和神经发生,这可能是癫海马组织胶质化、神经元可塑性的病理基础;BMP4可能在PTZ癫形成过程中起重要作用。     

一氧化氮对海人酸诱导大鼠癫痫发作脑组织海马结构HSP70表达的影响及意义

目的：研究海人酸诱导大鼠癫痫发作脑组织中一氧化氮（NO）与热休克蛋白70（HSP70）表达的关系。方法：利用免疫印迹分析法（westem blots)观察海人酸诱导大鼠癫痫发作及作用N－硝基－左旋精氨酸（LNNA）干预后脑组织海马结构HSP70的表达。结果：在癫痫发作过程中,预先用LNNA后,HSP70表达量较同一时间未干预的明显低。结论：在癫痫发作过程中,NO对HSP70表达有明显影响。     

胶质细胞谷氨酸转运体在大鼠点燃效应中的作用研究

目的 研究点燃形成过程中和点燃后大鼠海马中氨酸天门氨酸转运体（GLAST）和谷氨酸转运体1（GLT－1）的变化,进一步探讨癫痫的形成机制。方法 将78只雄性成年Wistar大鼠随机分为对照组（I组）和戊四氮（PTZ）组（Ⅱ组）。Ⅱ组腹腔注射阈下剂量的PTZ（335mg/kg）,每日1次,直到达到点燃标准;I组腹腔注射等量生理盐水。采有RT－PCR方法检测海马区GLAST和GLT－1mRNA的表达。结果 PTZ组点燃后,GLASTmRNA的表达下降,60天时恢复至对照组;与对照组比较,PTZ组GLT－1mRNA的表达,在给药后15天时开始上升,点燃后0小时和48小时时显著升高,此后呈下降趋势。60天时,两组比较无明显差异。结论 海马区胶质细胞谷氨酸转运体的下降可能与癫痫敏感性的形成有关。     

C-Fos mapping and EEG characteristics of multiple mice brain regions in pentylenetetrazol-induced seizure mice model

ABSTRACT

Purpose: To confirm different local brain activities characterized in pentylenetetrazol (PTZ)-induced seizure model.

Methods: we induced seizure response by a single dose of PTZ injection (45 mg/kg, i.p.). Local activity was recorded in different brain regions by EEG in time and c-Fos staining at different time points (0.5 h, 1 h, 2 h, 4 h) after PTZ treatment.

Results: EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of behavioral manifestations of seizures, the frequency and amplitude of the discharges on EEG were increasing gradually. The epileptic response on EEG immediately ended after reaching the maximum stage of seizures, followed by a short period of suppression. The labeling of c-Fos was enhanced in the medial prefrontal cortex, the piriform cortex, the amygdala, hippocampal CA1, CA3 and dentate gyrus, but inapparent in the striatum. The most potent changes in c-Fos were observed in cortex, amygdala nuclei, and dentate gyrus. EEG and c-Fos immunolabeling in neuronal activation showed discrepancies in the striatum. For each brain region, the maximum c-Fos labeling was observed at 2 h after injection and diminished at 4 h. The level of c-Fos immunoreactivity was even lower than the control group, which was accompanied by increased labeling of parvalbumin neurons (PVNs).

Conclusions: These findings validated PTZ-induced seizure as a seizure model with a specific spatial-temporal profile. Neuronal activity was enhanced and then subsequently inhibited during seizure evolution.

Abbreviations: AEDs: anti-epileptic drugs; AF: Alexa Fluor; CA1: Cornu Ammonis area 1; CA3: Cornu Ammonis area 3; DAB, 3: 3P-diaminobenzidine; DAPI: 4‘,6-diamidino-2-phenylindole; DG: dentate gyrus; EEG: electroencephalogram; GABA: gamma-aminobutyric acid; IEG: immediate early gene; mPFC: medial prefrontal cortex; NAc: nucleus accumbens; PB: phosphate buffer; PBS: phosphate buffered saline; PBST: phosphate buffered saline with Tween; PFA, paraformaldehyde; PTZ: pentylenetetrazol; PVN: parvalbumin neuron; ROI: regions of interest; SE: status epilepticus.     

Heat shock protein 27 shows a distinctive widespread spatial and temporal pattern of induction in CNS glial and neuronal cells compared to heat shock protein 70 and caspase 3 following kainate administration

Kainate-induced status epilepticus is associated with both apoptotic and necrotic cell death and induction of heat shock proteins (HSPs) in hippocampal and cortical regions of the rodent brain. In the present study we have examined the temporal, spatial and cellular expression patterns of mRNAs for the highly inducible HSPs, HSP70 and HSP27, together with the apoptotic marker, caspase 3 (CPP32) in rat brain after systemic administration of kainate. HSP70 mRNA was transiently induced in the forebrain by kainate, principally in the CA1, CA3 and hilar cells of the hippocampal formation, in piriform cortex and discrete thalamic nuclei. Maximal expression was seen at 8 h after kainate which then declined to background levels by 7 days. Labelling was predominantly neuronal. In contrast, HSP27 mRNA expression was more widespread. Intense labelling was observed in CA1, CA3 and the hilar region at 8 h after kainate but the expression profile for HSP27 mRNA expanded considerably with intense signals seen in corpus callosum, cortex and thalamus at 24 h post kainate. Emulsion autoradiographs indicated a predominantly glial localisation for HSP27 mRNA. In the hilus, a distinct subpopulation of interneurones were found to express HSP27 mRNA. CPP32 mRNA was upregulated in CA1, CA3 and hilus of the hippocampal formation and in piriform cortex. CPP32 mRNA expression was more restricted and similar in distribution to HSP70 mRNA being localised to neurones. The present study demonstrates the unique early expression of HSP27 mRNA by glial cells and distinct populations of neurones which extends beyond those in which HSP70 and CPP32 induction occurs with subsequent cell loss.     

Decreased expression of brain cAMP response element-binding protein gene following pentylenetetrazol seizure

The present study investigated whether the expression of the cAMP response element-binding protein (CREB) in the rat brain is altered following an acute self-limited seizure induced by pentylenetetrazol (PTZ). Male rats were injected intraperitoneally with a single convulsive dose (45 mg/kg) of PTZ, and the matched controls were given saline. For immunohistochemistry, animals were perfused with 4% parafomaldehyde at 24 h following PTZ seizures, and CREB immunoreactivity was examined in rat brain. For real-time RT-PCR, animals were sacrificed at 2 and 24 h and 1 week following PTZ seizures. Tissues from different rat brain regions were micropunched and subjected to real-time RT-PCR using Taqman probe. The CREB immunoreactive profiles were significantly decreased in CA3 and dentate gyrus of hippocampal formation, sensory cerebral cortex and thalamus at 24 h after PTZ seizures. Consistent with changes in CREB immunoreactivity, levels of CREB mRNA were significantly decreased in the hippocampus, cerebral cortex, amygdala and thalamus at 24 h after PTZ seizures. No significant change was found for CREB mRNA expression in these regions at 2 h or 1 week following PTZ seizures. These results show that a brief seizure caused a decline in CREB expression up to 24 h later.     

丹参对癫痫大鼠脑内热休克蛋白70表达的影响

目的 探讨丹参对癫痫发作所造成神经元损伤的作用及其机制。方法 采用戊四氮致痫模型,运用常规病理及电镜检查方法,对比丹参组与对照组神经元受损的情况;运用免疫组织化学方法,对比观察丹参组与对照组热休克蛋白（ＨＳＰ）７０表达的变化。结果 丹参组与对照组动物相比,大脑皮质及海马区异常神经元的数目明显减少（Ｐ〈０．０１）,超微结构的异常改变也明显减轻,同时丹参组动物脑内ＨＳＰ７０免疫反应阳性神经元的数目明显     

Anticonvulsant effect of neural regeneration peptide 2945 on pentylenetetrazol-induced seizures in rats

Neuron regeneration peptides (NRPs) are small synthetic peptides that stimulate neural proliferation, migration, and differentiation with no apparent toxicity and high target specificity in CNS. The aim of this study was to investigate the effect of NRP2945 on seizure activity induced by pentylenetetrazol (PTZ) in rats. Using behavioural assessment and electrocorticographical recordings, the effects of different doses of NRP2945 (5–20 µg/kg) were tested on seizure attacks induced by PTZ injection. In addition, the effect of NRP2945 was evaluated on the production of dark neurons and expression of GABA_A receptor α and β subunits and GAD-65 in the hippocampus and somatosensory cortex of the rat brain. Intraperitoneal injection of NRP2945 at 20 µg/kg prevented seizure attacks after PTZ injection. NRP2945 at doses of 5 and 10 µg/kg significantly decreased the total duration of seizure attacks and reduced the amplitude, duration and latency of epileptiform burst discharges induced by PTZ. In addition, the peptide significantly inhibited the production of dark neurons in the hippocampus and somatosensory cortex of epileptic rats. NRP2945 also significantly increased the expression of GABA_A receptor α and β subunits and GAD-65 in the hippocampus and somatosensory cortex compared with PTZ treated rats. This study indicates that NRP2945 is able to prevent the seizure attacks and neuronal injuries induced by PTZ, likely by stimulating GABA_A and GAD-65 protein expression and/or protecting these components of GABAergic signalling from PTZ-induced alteration. Further studies are needed to elucidate the potential role of NRP2945 as an antiepileptic drug.     

Distributions of heat shock protein-70 mRNAs and heat shock cognate protein-70 mRNAs after transient global ischemia in gerbil brain.

Distributions of heat shock protein (HSP)-70 mRNAs and heat shock cognate protein (HSC)-70 mRNAs after 10 min of transient global ischemia were investigated in gerbil forebrain by in situ hybridization using cloned cDNA probes selective for the mRNAs. Expression of HSP70 immunoreactivity was also examined in the same brains. In hippocampal CA1 neuronal cells, in which only a minimal induction of immunoreactive HSP70 protein was found, the strong hybridization for HSP70 mRNA disappeared at around 2 days before the death of CA1 cells became evident. Furthermore, in hippocampal CA3 cells, a striking induction of HSP70 mRNA was sustained even at 2 days along with a prominent accumulation of HSP70 immunoreactivity. In contrast to the case of HSP70 mRNA, HSC70 mRNA was present in most neuronal cells, especially dense in CA3 cells, of the sham brain. A co-induction of HSP70 and HSC70 mRNAs was observed in several cell populations after the reperfusion with a peak at 8 h, although the magnitude of HSC70 mRNA induction was lower than that of HSP70 mRNA, particularly in CA1 cells. The expression of HSC70 mRNA in CA1 cells also disappeared at around 2 days. All the induced signals of HSP70 and HSC70 mRNAs in other cell populations were diminished and returned to the sham level, respectively, by 7 days. These results are the first to show the time courses of distribution of HSP70 and HSC70 mRNAs and the immunoreactive HSP70 protein in the same gerbil brain after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of streptozotocin-induced diabetes and pentylenetetrazol-induced seizure on brain cortex (Ca2+)ATPase activity in rats

The aim of the present study was to obtain information about the effects of pentylenetetrazol-induced status epilepticus (SE) and streptozotocin-induced diabetes on brain cortex Ca(2+)ATPase activity. Treatment with pentylenetetrazol (PTZ) and streptozotocin (STZ) to rats resulted in significant decrease in brain cortex Ca(2+)ATPase activity as compared with controls. However, PTZ-treated diabetic rats had a slight but non-significant decrease in enzyme activity. Treatment with PTZ caused a more pronounced effect in inhibiting enzyme activity than that of treatment with STZ. Our results concluded that reduced brain cortex Ca(2+)ATPase activity following PTZ and STZ treatments to rats, may be an initial biochemical lesion which triggers a sequence of events which may culminate in cell death.     

Alterations in long-term seizure susceptibility and the complex of PSD-95 with NMDA receptor from animals previously exposed to perinatal hypoxia

PURPOSE: Perinatal hypoxia is an important cause of brain injury in the newborn and has consequences that are potentially devastating and life-long, such as an increased risk of epilepsy in later life. The postsynaptic density (PSD) is a cytoskeletal specialization involved in the anchoring of neurotransmitter receptors and in regulating the response of postsynaptic neurons to synaptic stimulation. The postsynaptic protein PSD-95 binds to the N-methyl-D-aspartate receptor (NMDAR) subunit, and hence activates cascades of NMDAR-mediated events, such as cyclic adenosine monophosphate (cAMP)-responsive element binding protein phosphorylation at serine-133 (pCREB(Serine-133)). Here we studied the effect of perinatal hypoxia on protein interactions involving PSD-95 and the NMDAR, as well as pCREB(Ser-133) expression at an age when the animals show increased seizure susceptibility. METHODS: Rats were assigned randomly to the control rats or the rats exposed to transient global hypoxia at postnatal day 10 (P10). At P45, some rats from both groups were treated with pentylenetetrazol (PTZ) intraperitoneally to test the seizure threshold, and others were studied for neuronal loss, pCREB(Serine-133), PSD-95, and NMDAR expressions in the midbrain, temporal cortex, and hippocampal CA1 subfield by using immunohistochemistry, co-immunoprecipitation, and immunoblotting techniques, respectively. RESULTS: The rats with prior exposure to perinatal hypoxia exhibited increased seizure susceptibility to PTZ, compared with the control rats. Associated with this long-term change in seizure susceptibility, selective neuronal loss was observed in the midbrain region while pCREB(Ser-133) expression was reduced in the midbrain, temporal cortex, and hippocampal CA1 subfield. Perinatal hypoxia led to a decrease in PSD-95 expression in the both midbrain and hippocampal CA1 subfield, with the exception of temporal cortex. Furthermore, the association between PSD-95 and NMDAR subunits (NR1, NR2A, and NR2B) in the hippocampal CA1 was also markedly altered by perinatal hypoxia. CONCLUSIONS: This study demonstrates that the decrease in several protein complexes that are essential components of the postsynaptic apparatus is associated with the observed increase in seizure susceptibility in adult rats with prior exposure to perinatal hypoxia. The results indicate that reductions in PSD-95 expression, PSD-95 binding of NMDAR subunits, and subsequent NMDAR-mediated CREB phosphorylation, particularly in hippocampal CA1, are long-term consequences of perinatal hypoxia and may, at least in part, contribute to perinatal hypoxia-induced reduction in seizure threshold.     

Differential effects of atorvastatin treatment and withdrawal on pentylenetetrazol-induced seizures

Purpose: Statins are selective inhibitors of 3‐hydroxyl‐3‐methyl‐glutaryl coenzyme A (HMG‐CoA) reductase, the rate‐limiting enzyme of the mevalonate pathway for cholesterol biosynthesis. Increasing evidence indicates that statins, particularly atorvastatin, are neuroprotective in several conditions, including stroke, cerebral ischemia, traumatic brain injury, and excitotoxic amino acid exposure. However, only a few studies have investigated whether statins modulate seizure activity. In the current study we investigated whether atorvastatin or simvastatin alters the seizures induced by pentylenetetrazol (PTZ), a classical convulsant. Methods: Adult male Wistar rats were treated with atorvastatin or simvastatin for 7 days (10 mg/kg/day). Seizure activity was induced by PTZ (60 mg/kg, i.p.), and evaluated by behavioral and electrographic methods. Cholesterol levels were determined by a standard spectrophotometric method. Blood–brain barrier (BBB) permeability was assessed by the fluorescein method. Atorvastatin levels in the plasma and cerebral cortex were determined by high‐performance liquid chromatography tandem mass spectrometry. Key Findings: We found that oral atorvastatin treatment increased the latency to PTZ‐induced generalized seizures. In contrast, when the 7‐day atorvastatin treatment was withheld for 1 day (i.e., atorvastatin withdrawal), PTZ‐induced seizures were facilitated, as evidenced by a decrease in the latency to clonic and generalized tonic–clonic seizures induced by PTZ. In contrast, simvastatin treatment for 7 days (10 mg/kg/day, p.o.), with or without withdrawal, did not alter PTZ‐induced seizures. Interestingly, the effects of atorvastatin treatment and withdrawal were not accompanied by changes in plasma or cerebral cortex cholesterol levels or in the BBB permeability. Atorvastatin levels in the plasma and cerebral cortex after 7 days of treatment were above the half maximal inhibitory concentration for inhibition of HMG‐CoA reductase, whereas atorvastatin was not detectable in the plasma or cerebral cortex following a 24 h washout period (atorvastatin withdrawal). Significance: We conclude that atorvastatin treatment and withdrawal have differential effects on pentylenetetrazol‐induced seizures, which are not related to changes in plasma or cerebral cortex cholesterol levels or in BBB permeability. Additional studies are necessary to evaluate the molecular mechanisms underlying our findings as well as its clinical implications.