Distinct Topographical Patterns of Spike-Wave Discharge in Transgenic and Pharmacologically Induced Absence Seizure Models

Absence seizures (AS) are generalized non-convulsive seizures characterized by a brief loss of consciousness and spike-and-wave discharges (SWD) in an electroencephalogram (EEG). A number of animal models have been developed to explain the mechanisms of AS, and thalamo-cortical networks are considered to be involved. However, the cortical foci have not been well described in mouse models of AS. This study aims to use a high density EEG in pathophysiologically different AS models to compare the spatiotemporal patterns of SWDs. We used two AS models: a pharmacologically induced model (gamma-hydroxybutyric acid, GHB model) and a transgenic model (phospholipase beta4 knock-out, PLCβ4 model). The occurrences of SWDs were confirmed by thalamic recordings. The topographical analysis of SWDs showed that the onset and propagation patterns were markedly distinguishable between the two models. In the PLCβ4 model, the foci were located within the somatosensory cortex followed by propagation to the frontal cortex, whereas in the GHB model, a majority of SWDs was initiated in the prefrontal cortex followed by propagation to the posterior cortex. In addition, in the GHB model, foci were also observed in other cortical areas. This observation indicates that different cortical networks are involved in the generation of SWDs across the two models.

Desynchronization of Theta Oscillations in Prefrontal Cortex during Self-stimulation of the Medial Forebrain Bundles in Mice

Stimulation of the medial forebrain bundle (MFB) can reinforce intracranial self-stimulation (ICSS) in rodents (i.e., reward-seeking behavior). The MFB stimulation produces a highly reliable behavioral output that enabled a clear distinction of the animal behavioral states between the non-ICSS and ICSS periods. However, the cortical states during these reward-seeking behaviors are not fully characterized in comparison to those during volitional behavior. This study was designed to characterize the cortical rhythms of and coherence between prefrontal cortex and hippocampus during the wheel-turning behavior reinforced by the ICSS in comparison to the wheel-turning without ICSS. We used a wheel for freely moving mice, which was programmed to deliver cathode currents through an electrode in the MFB at each one-quarter turn of the wheel to induce ICSS. The wheel-turning epochs were extracted from the pre-ICSS, ICSS and post-ICSS sessions and the prefrontal EEGs and the hippocampal LFPs in the epochs were analyzed with power and synchronization analyses. During the ICSS, the EEG power decreased at 6~10 Hz in the prefrontal cortex, while was not significantly altered in the hippocampus. Furthermore, we found that the phase synchrony between the prefrontal cortex and the hippocampus corresponding to information transmission between the two regions during reward-seeking motion decreased preceding MFB stimulation reinforced by ICSS. Our findings suggest that theta-activity can be reliably dissociated from active behavior if the animal is involved in self-stimulation.

Poly(rC) binding protein 2 acts as a negative regulator of IRES-mediated translation of Hr mRNA

During the hair follicle (HF) cycle, HR protein expression is not concordant with the presence of the Hr mRNA transcript, suggesting an elaborate regulation of Hr gene expression. Here we present evidence that the 5′ untranslated region (UTR) of the Hr gene has internal ribosome entry site (IRES) activity and this activity is regulated by the binding of poly (rC) binding protein 2 (PCBP2) to Hr mRNA. Overexpression and knockdown of PCBP2 resulted in a decrease in Hr 5′ UTR IRES activity and an increase in HR protein expression without changing mRNA levels. We also found that this regulation was disrupted in a mutant Hr 5′ UTR that has a mutation responsible for Marie Unna hereditary hypotrichosis (MUHH) in both mice and humans. These findings suggest that Hr mRNA expression is regulated at the post-transcriptional level via IRES-mediated translation control through interaction with PCPB2, but not in MUHH.

Pulse-train Stimulation of Primary Somatosensory Cortex Blocks Pain Perception in Tail Clip Test

Human studies of brain stimulation have demonstrated modulatory effects on the perception of pain. However, whether the primary somatosensory cortical activity is associated with antinociceptive responses remains unknown. Therefore, we examined the antinociceptive effects of neuronal activity evoked by optogenetic stimulation of primary somatosensory cortex. Optogenetic transgenic mice were subjected to continuous or pulse-train optogenetic stimulation of the primary somatosensory cortex at frequencies of 15, 30, and 40 Hz, during a tail clip test. Reaction time was measured using a digital high-speed video camera. Pulse-train optogenetic stimulation of primary somatosensory cortex showed a delayed pain response with respect to a tail clip, whereas no significant change in reaction time was observed with continuous stimulation. In response to the pulse-train stimulation, video monitoring and local field potential recording revealed associated paw movement and sensorimotor rhythms, respectively. Our results show that optogenetic stimulation of primary somatosensory cortex at beta and gamma frequencies blocks transmission of pain signals in tail clip test.

A Novel Visualization Method for Sleep Spindles Based on Source Localization of High Density EEG

Equivalent dipole source localization is a well-established approach to localizing the electrical activity in electroencephalogram (EEG). So far, source localization has been used primarily in localizing the epileptic source in human epileptic patients. Currently, source localization techniques have been applied to account for localizing epileptic source among the epileptic patients. Here, we present the first application of source localization in the field of sleep spindle in mouse brain. The spatial distribution of cortical potential was obtained by high density EEG and then the anterior and posterior sleep spindles were classified based on the K-mean clustering algorithm. To solve the forward problem, a realistic geometry brain model was produced based on boundary element method (BEM) using mouse MRI. Then, we applied four different source estimation algorithms (minimum norm, eLORETA, sLORETA, and LORETA) to estimate the spatial location of equivalent dipole source of sleep spindles. The estimated sources of anterior and posterior spindles were plotted in a cine-mode that revealed different topographic patterns of spindle propagation. The characterization of sleep spindles may be better be distinguished by our novel visualization method.

Pupil Size in Relation to Cortical States during Isoflurane Anesthesia

In neuronal recording studies on anesthetized animals, reliable measures for the transitional moment of consciousness are frequently required. Previous findings suggest that pupil fluctuations reflect the neuronal states during quiet wakefulness, whose correlation was unknown for the anesthetized condition. Here, we investigated the pupillary changes under isoflurane anesthesia simultaneously with the electroencephalogram (EEG) and electromyogram (EMG). The pupil was tracked by using a region-based active contour model. The dose was given to the animal in a stepwise increasing mode (simulating induction of anesthesia) or in a stepwise decreasing mode (simulating emergence of anesthesia). We found that the quickly widening pupil action (mydriasis) characterizes the transitional state in anesthesia. Mydriasis occurred only in the light dose in the emergence phase, and the events were accompanied by an increase of burst activity in the EEG followed by EMG activity in 47% of the mydriasis events. Our findings suggest that recording such pupil changes may offer a noncontact monitoring tool for indexing the transitional state of the brain, particularly when a lower threshold dose is applied.

Pupil Size in Relation to Cortical States during Isoflurane Anesthesia

In neuronal recording studies on anesthetized animals, reliable measures for the transitional moment of consciousness are frequently required. Previous findings suggest that pupil fluctuations reflect the neuronal states during quiet wakefulness, whose correlation was unknown for the anesthetized condition. Here, we investigated the pupillary changes under isoflurane anesthesia simultaneously with the electroencephalogram (EEG) and electromyogram (EMG). The pupil was tracked by using a region-based active contour model. The dose was given to the animal in a stepwise increasing mode (simulating induction of anesthesia) or in a stepwise decreasing mode (simulating emergence of anesthesia). We found that the quickly widening pupil action (mydriasis) characterizes the transitional state in anesthesia. Mydriasis occurred only in the light dose in the emergence phase, and the events were accompanied by an increase of burst activity in the EEG followed by EMG activity in 47% of the mydriasis events. Our findings suggest that recording such pupil changes may offer a noncontact monitoring tool for indexing the transitional state of the brain, particularly when a lower threshold dose is applied.

Synergistic Effect of Interleukin-6 and Hyaluronic Acid on Cell Migration and ERK Activation in Human Keratinocytes

Wound healing is initiated and progressed by complex integrated process of cellular, physiologic, and biochemical events, such as inflammation, cell migration and proliferation. Interleukin 6 (IL-6) is a multifunctional cytokine, and it could regulate the inflammatory response of wound healing process in a timely manner. Hyaluronic acid (HA) is an essential component of the extracellular matrix, and contributes significantly to cell proliferation and migration. The purpose of this study was to investigate the effects of IL-6 or/and HA on the cell migration process in human keratinocytes. Combining IL-6 and HA significantly increased the cell migration in scratch based wound healing assay. The phosphorylation of extracellular-signal-regulated kinase (ERK) was significantly increased after 1 hr of IL-6 and HA treatment, but the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was not. We also found that significant increase of the NF-kappaB translocation from cytoplasm into nucleus after 1 hr of IL-6 or/and HA treatments. This study firstly showed that synergistic effects of combining IL-6 and HA on the cell migration of wound healing by activation of ERK and NF-kappaB signaling. Further studies might be required to confirm the synergistic effects of HA and IL-6 in the animal model for the development of a novel therapeutic mixture for stimulation of wound healing process.

A Case of Epidural Abscess Complicated from Acute Mastoiditis Caused by Streptococcus pneumoniae / 소아감염

Acute otitis media (AOM) is one of the most common childhood infectious diseases. Despite antibiotic treatment for AOM, AOM and its complication still continue to develop. Acute mastoiditis is a serious complication of AOM and epidural abscess constitutes the commonest of all intracranial complication of AOM. Neurological complication of acute mastoiditis are rare but can be life threatening. Their presentation may be masked by the use of antibiotics. We report the rare case of acute otitis media progressing to acute mastoiditis, epidural abscess formation and lateral sinus thrombophlebitis caused by Streptococcus pneumoniae in a child. She was admitted with acute otitis media with fever. Despite proper antibiotics, acute mastodititis and epidural abscess were developed, and after surgical drainage and antibiotics therapy she was recovered without sequalae.

Comparison among Known Severity Scoring Scales in the Evaluation of Acute Gastroenteritis in Children / 소아감염

PURPOSE: This study aimed to evaluate the disease severity of children suffering from gastroenteritis using different scales. The results are compared and subsequently classified on the basis of the type of virus causing the disease in order to investigate the differences in clinical characteristics and disease severity according to pathogen. METHOD: This study was conducted prospectively with patients under 5 years of age diagnosed with acute gastroenteritis and hospitalized at 9 medical institutions in 8 regions across the Republic of Korea. Disease severity was evaluated using the Vesikari Scale, the Clark Scale, and the modified Flores Scale. Fecal samples collected from patients were used to detect rotavirus and enteric adenovirus by enzyme immunoassay, and for RT-PCR of norovirus, astrovirus, and sapovirus. RESULTS: There were a total of 214 patients with a male : female ratio of 1.58 : 1, of which 35 were under the age of 6 months (16.4%), 105 were aged 6-23 months (49.1%), and 74 were aged 24-59 months (34.5%). The rate of concordance between the Vesikari and Clark Scales was 0.521 (P<0.001) and, in severe cases, the Vesikari Scale was 60.7% and Clark Scale was 2.3%, indicating that the Clark Scale was stricter in the evaluation of severe cases. CONCLUSIONS: In children with gastroenteritis, there were differences in disease severity based on the scale used. Therefore, to achieve consistent results among researchers, either only a single scale or a measure of all scales should be used to determine disease severity.

Single Nucleotide Deletion Mutation of KCNH2 Gene is Responsible for LQT Syndrome in a 3-Generation Korean Family

Long QT syndrome (LQTS) is characterized by the prolongation of the QT interval in ECG and manifests predisposition to life threatening arrhythmia which often leads to sudden cardiac death. We encountered a 3-generation family with 5 affected family members in which LQTS was inherited in autosomal dominant manner. The LQTS is considered an ion channel disorder in which the type and location of the genetic mutation determines to a large extent the expression of the clinical syndrome. Upon screening of the genomic sequences of cardiac potassium ion channel genes, we found a single nucleotide C deletion mutation in the exon 3 of KCNH2 gene that co-segregates with the LQTS in this family. This mutation presumably resulted in a frameshift mutation, P151fs+15X. This study added a new genetic cause to the pool of mutations that lead to defected potassium ion channels in the heart.

The Hairless Gene: A Putative Navigator of Hair Follicle Development

The Hairless (HR) gene regulates the expression of several target genes as a transcriptional corepressor of nuclear receptors. The hair follicle (HF), a small independent organ of the skin, resides in the epidermis and undergoes regenerative cycling for normal hair formation. HF development requires many genes and signaling pathways to function properly in time and space, one of them being the HR gene. Various mutations of the HR gene have been reported to cause the hair loss phenotype in rodents and humans. In recent studies, it has been suggested that the HR gene is a critical player in the regulation of the hair cycle and, thus, HF development. Furthermore, the HR gene is associated with the Wnt signaling pathway, which regulates roliferation and differentiation of cells and plays an essential role in hair and skin development. In this review, we summarize the mutations responsible for human hair disorders and discuss the roles of the HR gene in HF development.