• Annals of Clinical Neurophysiology
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• 제1권2호
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• pp.147-153
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• 1999

Hippocampal slice models can be a powerful tool to study the mechanism of partial epilepsy. Despite the loss of connection with the rest of the brain, in vitro hippocampal slice preparations allow detailed physiological and pharmacological studies, which would be impossible, in vivo. There are several methods to induce electrographic seizures on hippocampal slice models. Those are electrical pulse train stimulation, 0 $Mg^{2+}$ artificial cerebrational fluid and high concentration of extracelluar $K^+$ on bath. Among them, the electrically triggered seizure may mimic the physiological communication between neuronal populations without any deterioration of normal physiologic and chemical status of the hippocampal slice models. Presumably, such communication from hyperexcitable areas to other neuronal populations is involved in the development of epilepsy. Electrographic seizures in hippocampal slice models occur in the network of neurons that are involved in epileptic seizures in the hippocampus in vivo. Because these models have many advantages and are very valuable to research of epileptogenesis on partial epilepsy, I would like to introduce the electrophysiological methods to induce electrographic seizure or epilepsy on hippocampal slice models briefly in this paper.

• Archives of Pharmacal Research
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• 제27권5호
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• pp.524-530
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• 2004

Epilepsy or the occurrence of spontaneous recurrent epileptiform discharges (SREDs, seizures) is one of the most common neurological disorders. Shift in the balance of brain between excitatory and inhibitory functions due to different types of structural or functional alterations may cause epileptiform discharges. N-Methyl-D-aspartate (NMDA) receptor dysfunctions have been implicated in modulating seizure activities. Seizures and epilepsy are clearly dependent on elevated intracellular calcium concentration ([C $a^{2+}$]$_{i}$ ) by NMDA receptor activation and can be prevented by NMDA antagonists. This perturbed [C $a^{2+}$]$_{i}$ levels is forerunner of neuronal death. However, therapeutic tools of elevated [C $a^{2+}$]$_{i}$ level during status epilepticus (SE) and SREDs have not been discovered yet. Our previous study showed fast inhibition of ginseng total saponins and ginsenoside R $g_3$ on NMDA receptor-mediated [C $a^{2+}$]$_{i}$ in cultured hippocampal neurons. We, therefore, examined the direct modulation of ginseng on hippocampal neuronal culture model of epilepsy using fura-2-based digital $Ca^{2+}$ imaging and neuronal viability assays. We found that ginseng total saponins and ginsenoside R $g_3$ inhibited $Mg^{2+}$ free-induced increase of [C $a^{2+}$]$_{i}$ and spontaneous [C $a^{2+}$]$_{i}$ oscillations in cultured rat hippocampal neurons. These results suggest that ginseng may playa neuroprotective role in perturbed homeostasis of [C $a^{2+}$]$_{i}$ and neuronal cell death via the inhibition of NMDA receptor-induced SE or SREDs.d SE or SREDs..

• 응용통계연구
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• 제37권2호
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• pp.139-155
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• 2024

본 연구는 좌측 해마 경화를 보인 내측두엽 뇌전증(left mTLE, mesial temporal lobe epilepsy with left hippocampal sclerosis) 환자군과 우측 해마 경화를 보인 내측두엽 뇌전증(right mTLE, mesial temporal lobe epilepsy with right hippocampal sclerosis) 환자군 그리고 건강한 대조군(healthy controls; HC)으로부터 측정한 뇌자도(magnetoencephalography; MEG) 데이터로 각 그룹을 분류하는 다중 분류 작업에 다양한 인공신경망을 적용하고 그 결과를 비교해 보고자 하였다. 합성곱 신경망, 순환 신경망 그리고 그래프 신경망으로 모델링한 결과, k-fold 정확도 평균은 합성곱 신경망 기반 모델, 그래프 신경망 기반 모델, 순환 신경망 기반 모델 순으로 우수하였다. 또한, 수행 시간은 순환 신경망 기반 모델, 그래프 신경망 기반 모델, 합성곱 신경망 기반 모델 순으로 우수하였다. 정확도 성능과 시간 면에서 모두 좋은 수치를 보이며, 네트워크 데이터의 확장성이 뛰어난 그래프 신경망이 앞으로 뇌 연구에 활용되기 적합한 모델임을 강조하고자 한다.

• Korean Journal of Radiology
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• 제25권4호
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• pp.374-383
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• 2024

Objective: To evaluate the diagnostic performance and image quality of 1.5-mm slice thickness MRI with deep learningbased image reconstruction (1.5-mm MRI + DLR) compared to routine 3-mm slice thickness MRI (routine MRI) and 1.5-mm slice thickness MRI without DLR (1.5-mm MRI without DLR) for evaluating temporal lobe epilepsy (TLE). Materials and Methods: This retrospective study included 117 MR image sets comprising 1.5-mm MRI + DLR, 1.5-mm MRI without DLR, and routine MRI from 117 consecutive patients (mean age, 41 years; 61 female; 34 patients with TLE and 83 without TLE). Two neuroradiologists evaluated the presence of hippocampal or temporal lobe lesions, volume loss, signal abnormalities, loss of internal structure of the hippocampus, and lesion conspicuity in the temporal lobe. Reference standards for TLE were independently constructed by neurologists using clinical and radiological findings. Subjective image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were analyzed. Performance in diagnosing TLE, lesion findings, and image quality were compared among the three protocols. Results: The pooled sensitivity of 1.5-mm MRI + DLR (91.2%) for diagnosing TLE was higher than that of routine MRI (72.1%, P < 0.001). In the subgroup analysis, 1.5-mm MRI + DLR showed higher sensitivity for hippocampal lesions than routine MRI (92.7% vs. 75.0%, P = 0.001), with improved depiction of hippocampal T2 high signal intensity change (P = 0.016) and loss of internal structure (P < 0.001). However, the pooled specificity of 1.5-mm MRI + DLR (76.5%) was lower than that of routine MRI (89.2%, P = 0.004). Compared with 1.5-mm MRI without DLR, 1.5-mm MRI + DLR resulted in significantly improved pooled accuracy (91.2% vs. 73.1%, P = 0.010), image quality, SNR, and CNR (all, P < 0.001). Conclusion: The use of 1.5-mm MRI + DLR enhanced the performance of MRI in diagnosing TLE, particularly in hippocampal evaluation, because of improved depiction of hippocampal abnormalities and enhanced image quality.

• 대한핵의학회지
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• 제37권1호
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• pp.24-33
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• 2003

Finding epileptogenic zone is the most important step for the successful epilepsy surgery. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and single photon emission computed tomography (SPECT) can be used in the localization of epileptogenic foci. In medial temporal lobe epilepsy, the diagnostic sensitivity of FDG-PET and ictal SPECT is excellent. However, detection of hippocampal sclerosis by MRI is so certain that use of FDG-PET and ictal SPECT in medial temporal lobe epilepsy is limited for some occasions. In neocortical epilepsy, the sensitivities of FDG-PET or ictal SPECT are fair. However, FDG-PET and ictal SPECT can have a crucial role in the localization of epileptogenic foci for non-lesional neocortical epilepsy. Interpretation of FDG-PET has been recently advanced by voxel-based analysis and automatic volume of interest analysis based on a population template. Both analytical methods can aid the objective diagnosis of epileptogenic foci. Ictal SPECT was analyzed using subtraction methods and voxel-based analysis. Rapidity of injection of tracers, ictal EEG findings during injection of tracer, and repeated ictal SPECT were important technical issues of ictal SPECT. SPECT can also be used in the evaluation of validity of Wada test.

• Journal of Korean Neurosurgical Society
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• 제30권11호
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• pp.1300-1307
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• 2001

Purposes : This study reports the possible causes of seizure recurrence in patients underwent previous epilepsy surgery, and surgical strategy for resection of the additional epileptogenic zone locating at the distant area to the site of first resection. Methods : A total of 10 patients with previous surgery due to intractable epilepsy were studied. Five of these underwent standard temporal lobectomy, four extratemporal resection, and one corticoamygdalectomy. Seizure outcome of these were class III-IV. Evaluation methods for reoperation included MRI, 3D-surface rendering of MRI, PET, prologned video-EEG recording with surface electrodes and subdural grid electrodes. Additional resection was done in the frontal lobe in two, in the temporal lobe in three, in the parietal lobe in two, and in the supplementary sensori-motor area in two. Tumor in the superior frontal gyrus in the left hemisphere was removed in one patient. Extent of resection was decided based on the results of ictal subdural grid EEGs and MRI findings. Awake anesthesia and electrocortical stimulation were performed in the two patients for defining the eloquent area. Results : Histopathologic findings revealed extratemporal cortical dysplasia in six, hippocampal sclerosis and cortical dysplasia of the temporal neocortex in one, neuronal gliosis in two, and meningioma in one. Previous pathology of the five patients with cortical dysplasia in the second operation was hippocampal sclerosis plus cortical dysplasia of the temporal neocortex. After reoperation, seizure outcomes were class I in six, class II in three, class III in one at the mean follow-up period of 17.5 months. Characteristically, patients in class II-III after reoperation showed histopathologic findings of hippocampal sclerosis plus temporal neocortical cortical dysplasia plus extratemporal cortical dysplasia. Conclusions : Seizure recurrence after epilepsy surgery was related with the presence of an additional epileptogenic zone distant to the site of first operation, and the majority of the histopathology of the surgical specimens was cortical dysplasia. In particular, hippocampal sclerosis plus temporal neocortical cortical dysplasia was highly related with seizure recurrence in patients with previous operation. In these patients, multimodal evaluation methods were necessary in defining the additional epileptogenic zone.

• Investigative Magnetic Resonance Imaging
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• 제6권1호
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• pp.47-54
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• 2002

목적 해마의 위축(hippocampal atrophy)은 해마경화증(hippocampal sclerosis)의 가장 특징적인 병리학적 소견의 하나로서, 이의 진단하기 위하여 해마의 자기공명(MR) 영상이 필수적이다. 본 연구에서는 정상성인과 해마경화증 환자에서 해마에 대한 MR부피를 측정하여 해마 경화증의 진단기준을 제시하고자 하였다. 대상 및 방법 신경학적으로 정상이며 MR 영상에서 뇌실질부위에 이상소견이 없는 정상 성인 30명 (20-46세 , 남자 16명, 여자 14명)을 대상으로 하여 양측해마의 부피를 측정하고 그 분포를 구하였다. 또한 측두엽 간질환자로서 최종진단이 해마경화증으로 판정된 28명의 환자(9-55세, 남자 14명, 여자 14명)를 대상으로 하여 해마부피를 측정한 후 각각의 좌우 차를 구하고 정상분포와 비교하였다. 결과 : 한국성인의 해마의 정상부피의 평균치와 표준편차는 남자가 우측 $2.20{\pm}0.73\textrm{cm}^3$, 좌측 $2.17{\pm}0.72$ $\textrm{cm}^3$ 좌우 차 $0.14{\pm}0.11\textrm{cm}^3이었고$, 여자가 우측이 $2.27{\pm}0.47\textrm{cm}^3$, 좌측이 $2.23{\pm}0.48$ 서울대학교 의과대학 방사선과학교실 좌우 차 $0.19{\pm}0.13\textrm{cm}^3이었다.$ 좌우와 남녀간에 통계학적으로 유의한 차이는 얼었다. 해마경화증 환자에서의 해마의 부피는 전체 해마경화증 환자 군에서 평균과 표준 편차가 $1.46{\pm}0.60\textrm{cm}^3$, 좌우 차 $0.51{\pm}0.41\textrm{cm}^3$ 였으며, 우측 해마경화증 환자 군에서 평균이 $139{\pm}0.58$, $\textrm{cm}^3$, 좌우 차 $0.38{\pm}0.27\textrm{cm}^3$, 좌측 해마경화증 환자 군에서 평균이 $1.56{\pm}0.65\textrm{cm}^3$, 좌우 차 $0.71{\pm}0.52\textrm{cm}^3$ 였다. 해마경화증 환자군과 정상성인군의 부피의 절대치와 좌우 부피 차의 분포를 비교해 본 결과 해마부피분포는 정상 성인군과 해마경화증 환자군 사이에 많은 경우에서 절대치가 중첩되어 해마부피분포의 절대치는 진단기준으로서 유용하지 않았다. 좌우 부피 차 0.4 $\textrm{cm}^3$ 이상을 해마위축의 기준으로 할 때 MR-based volumetry 만의 민감도와 특이도는 각각 0.61, 0.90로 좌우 부피 차 $0.4{\;}\textrm{cm}^3$ 이상이 적절한 진단기준으로 생각되었다. $0.4{\;}\textrm{cm}^3$ 이상의 좌우 부피차를 보이는 모든 증례에서 육안적으로도 해마위축이 뚜렷이 나타났다. 결론 : MR영상을 이용한 해마의 부피측정은 해마경화증 환자의 진단에 있어 육안적인 MR 진단이 어려운 제한된 경우에만 실제적 도움을 줄 수 있는 보조적인 방법으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제23권4호
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• pp.281-289
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• 2019

Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

• Journal of Ginseng Research
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• 제47권3호
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• pp.390-399
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• 2023

Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.

• Journal of Korean Neurosurgical Society
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• 제29권12호
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• pp.1650-1656
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• 2000

Objective : Little consensus exists concerning which temporal lobe structures need to be resected or how much resection should be done during hippocampal resection. The purpose of this study is to identify whether the extent of hippocampal resection influences seizure after anterior temporal lobectomy. Materials and Methods : The extent of hippocampal resection was assessed in 96 patients who underwent temporal lobectomy for medically intractable complex partial seizures originating from a unilateral seizure focus in the anteromesial temporal lobe. Patients who had structural lesion were excluded from the study. Postoperative magnetic resonance imaging in the coronal and saggital planes were used to quantify the extent of the hippocampal and lateral cortical resection. The patients were divided into two groups. Patients who underwent hippocampal resection to the level of the cerebral peduncle were included in the partial resection group, and those who had resection to the level of the colliculus were assigned to total resection group. Seizure outcomes were defined according to the Engel classification and compared between the two groups. Neuropsychologic outcomes in the selected cases were reviewed. Results : The over-all seizure-free outcome(Engel classification 1) was accomplished in 75%(72/96) of the patients (mean duration of follow-up, 36.8 months). The total hippocampectomy group had a statistically superior seizure outcome than the partial hippocampectomy group(87.3% versus 58.5% seizure-free, p-value=0.001). Also, younger patients had a more favorable outcome. Other variables such as laterality, the extent of lateral cortical resection, age at onset and gender were not significant. The pre- and postoperative memory functions were evaluated in 24 patients. A worse postoperative memory outcome was associated with partial hippocampectomy. However this was not acceptable due to a former bias. Conclusion : The result of this study conforms that aggressive hippocampectomy resulted in a better seizure outcome.