EphA/ephrin-A mediated signaling has emerged as a key mechanism regulating axon guidance and topographic mapping, particularly in the well-characterized visual system from the retina to the superior colliculus (SC). In this study, EphA8 bacterial artificial chromosome (BAC) was manipulated to contain a floxed eGFP and human ephrin-A5 expression cassette using homologous recombination method. In the mice containing the recombinant BAC, it was shown that GFP is expressed in an anterior>posterior gradient in the SC. Furthermore, when these mice were crossed with the transgenic mice expressing Cre under the EphA8 promoter, it was evident that a GFP expression cassette was eliminated, and that human ephrin-A5 was ectopically expressed in the anterior region of the SC. This transgenic model would be useful to analyze the role of ephrin-A5 in the SC during the retinocollicular topography formation.
Animals ; Axons ; Chromosomes, Artificial, Bacterial ; Ephrin-A5 ; Homologous Recombination ; Humans ; Mice ; Mice, Transgenic ; Retina ; Superior Colliculi

Eph receptors and their ligands, ephrins, are abundantly expressed in neuroepithelial cells of the early embryonic brain. Overstimulation of Eph signaling in vivo increases apoptotic cell death of neuroepithelial cells, whereas null mutation of the Eph gene leads to the development of a larger brain during embryogenesis. Thus, it appears that Eph-ephrin signaling plays a role in regulating apoptotic cell death of neuroepithelial cells, thereby influencing brain size during embryonic development. Interestingly, Eph-ephrin signaling is bi-directional, with forward signaling from ephrin- to Eph-expressing cells and reverse signaling from Eph- to ephrin-expressing cells. However, it is not clear whether this forward or reverse signaling plays a role in regulating the size of the neuroepithelial cell population during early brain development. Also, Eph receptors and their corresponding ligands are mutually exclusive in their expression domains, and they encounter each other only at interfaces between their expression domains. This expression pattern may be a critical mechanism for preventing overstimulation of Eph-ephrin signaling. Nevertheless, Eph receptors are co-expressed with their corresponding ligands in certain brain regions. Recently, two studies demonstrated that brain region-specific apoptosis may be triggered by the overlapping expression of Eph and ephrin, a theme that will be explored in this mini-review.
Apoptosis ; Brain ; Cell Death ; Embryonic Development ; Ephrins ; Female ; Ligands ; Neuroepithelial Cells ; Pregnancy ; Receptor, EphA1 ; Receptors, Eph Family

The clinical cases of 6 patients suffering with chorea after acute carbon monoxide (CO) poisoning were reviewed. There were 2 men and 4 women, and the age at onset ranged from 11 to 60 (mean 33.0) years. All the patients except one were associated with mild delayed CO encephalopathy. The latency period between CO poisoning and the onset of chorea was 10 to 30 (mean 21.7) days. The duration of chorea after CO poisoning was 14 to 90 (mean 39.8) days. The brain CT findings were bilateral low- density lesions in the basal ganglia and/or in the white matter of the cerebral cortex, and there was no correlation between the lesion sites on the imagings and the development of chorea. Neuroleptic agents alleviated the chorea and the patients did not relapse after neuroleptic agents were halted.
Acute Disease ; Adolescent ; Adult ; Brain Diseases/etiology/radiography ; Carbon Monoxide Poisoning/*complications/radiography ; Chorea/*etiology/radiography ; Female ; Human ; Male ; Middle Aged ; Tomography, X-Ray Computed

This study was aimed to map the 1 kb cis-acting DNA of ephA8 gene, which regulates the spatial and temporal expression in the anterior mesencephalon. It was demonstrated that the 1 kb ephA8 enhancer DNA was sufficient to drive the lacZ expression to the anterior mesencephalon under the human beta-globin minimal promoter. It was also found that a 180 bp within the 1 kb enhancer DNA was highly conserved between human and mouse, and that this 180 bp DNA was capable of inducing the lacZ expression in the anterior mesencephalon under the ephA8 or human beta-globin basal promoter. Further analysis using 5'-55 bp deleted or 3'-55 bp deleted mutant DNA revealed that the 55 bp portion present at the 3'-end of 180 bp DNA was critical for the regulation of ephA8 gene expression in the anterior mesencephalon. Taken together, these results indicate that 180 bp ephA8 enhancer DNA contains cisacting elements for the regulation of ephA8 gene expression in the anterior mesencephalon.
Animals ; beta-Globins ; DNA ; Gene Expression* ; Humans ; Mesencephalon* ; Mice ; Mice, Transgenic

The Eph family is thought to exert its function through the complementary expression of receptors and ligands. The dorsal mesencephalon appears to be segmented into two broad regions demarcated by the mutually exclusive expression of EphA receptors and ephrinA ligands. In this study, we analyzed transgenic embryos expressing ephrinA2 in the anterior region of the developing midbrain where the EphA8 receptor is expressed. First, 1% of transgenic embryos showed cephalic neural tube closure defects. Second, it was confirmed that mis-expression of ephrin-A2 in the anterior mesencephalon induced an increase in the EphA8 tyrosine kinase activity. Accordingly, an increased MAPK activity was also detected in the anterior mesencephalon of E14.5 transgenic embryo. Third, cell adhesion assay revealed that mis-expression of ephrinA2 promoted cell attachment to fibronectin. Taken together, these findings suggest that co-expression of EphA receptors and ephrinA ligands significantly alter cell behaviors including cell adhesion.
Animals ; Cell Adhesion ; Diencephalon* ; Embryonic Structures ; Ephrin-A2 ; Fibronectins ; Humans ; Ligands ; Mesencephalon* ; Mice* ; Mice, Transgenic ; Neural Tube ; Protein-Tyrosine Kinases ; Receptor, EphA8 ; Receptors, Eph Family

PURPOSE: We explored whether the deviation angle in patients with intermittent exotropia was greater when the prism adaptation test was used rather than the prism cover test. METHODS: From January 2013 to December 2017, we performed the prism cover and adaptation tests on patients with intermittent exotropia. If the deviation angle increased by more than 5 PD after the prism adaptation test, surgery was performed. The outcomes of patients followed-up for more than 1 year after surgery were analyzed retrospectively. RESULTS: In total, 76 of 100 patients (76.0%) exhibited deviation angle increases of over 5 PD, the mean increase was 9.8 ± 6.3 prism diopters (PD) for near vision and 3.6 ± 3.5 PD for distance vision. Satisfactory motor alignment was achieved in 57 patients; 42 were undercorrected and 1 was overcorrected. The success rate was 62.5% in the non-responder group (n = 24, patients in whom the deviation angle did not increase after prism adaptation) and 68.9% in the full augmentation group (n = 45, in whom the deviation angle was increased). In the partial augmentation group (n = 31), where the surgical target was a 50% increase in the deviation angle, the success rate was lower than in the other groups. CONCLUSIONS The preoperative prism adaptation test can be used to determine the angle of deviation and improves the surgical outcomes of patients with intermittent exotropia.

In this study, we show that ANKS1A is specifically expressed in the brain endothelial cells of adult mice. ANKS1A deficiency in adult mice does not affect the differentiation, growth, or patterning of the cerebrovascular system; however, its absence significantly impacts the cerebrovascular system of the aged brain. In aged ANKS1A knock-out (KO) brains, vessel lesions exhibiting cerebral cavernous malformations (CCMs) are observed.In addition, CCM-like lesions show localized peripheral blood leakage into the brain. The CCM-like lesions reveal immune cells infiltrating the parenchyma. The CCM-like lesions also contain significantly fewer astrocyte endfeets and tight junctions, indicating that the integrity of the BBB has been partially compromised. CCM-like lesions display increased fibronectin expression in blood vessels, which is also confirmed in cultured endothelial cells deficient for ANKS1A. Therefore, we hypothesize that ANKS1A may play a role in maintaining or stabilizing healthy blood vessels in the brain during aging.

Background: and Purpose: Hippocampal atrophy (HA) resulting from a central nervous system (CNS) infection might be a relevant lesion responsible for the clinical characteristics of medial temporal lobe epilepsy. Methods: The clinical characteristics of 54 patients with CNS infection-related medial temporal lobe epilepsy (MTLE) with isolated HA (CNS infection group) and 155 patients with conventional MTLE with HA (conventional group) were compared retrospectively. CNS infection alone and bilateral involvement of the HA were analyzed as prognostic factors, in addition to the detailed clinical characteristics, such as limbic aura and the presence and proportion of each type of automatism, between the two groups, and both medical and surgical prognoses were separately considered. A logistic regression analysis was performed. Results: A statistical analysis including all clinical factors, including CNS infection with bilateral HA, did not reveal significant differences between the two groups. An analysis comparing the prognosis of the two groups based on good or poor prognosis among patients who received medical treatment and good or poor outcomes among patients who received surgical treatment did not produce significant differences. Conclusions In addition to bilateral HA, CNS infection alone was not a poor prognostic factor for the CNS infection-related epilepsy with HA group compared with the conventional MTLE with HA group. Based on these negative results, HA is a plausible and relevant lesion with similar clinical characteristics to HA in patients with conventional MTLE. Therefore, CNS infection-related MTLE with isolated HA might represent another subtype of MTLE with HA with a different etiology.

Eyelid myoclonia with absence is a distinct syndrome of idiopathic generalized epilepsy, characterized by the triad of eyelid myoclonia associated with brief absences, generalized discharges of 3-6 Hz polyspike and slow waves, which are mainly precipitated by eye closure or photosensitivity. We experienced two women with eyelid myoclonia with absence, who typically showed fixation off sensitivity and catatmenial exacerbation. Carabamazepine monotherapy aggravated the seizure frequency and resulted in nonconvulsive status epilepticus. These cases have not previously been reported in Korea.
Epilepsy, Generalized ; Eyelids* ; Female ; Humans ; Korea ; Seizures ; Status Epilepticus*

Limbic encephalitis has been reported usually as an autoimmune complication related to onconeuronal antigen of underlying cancer with poor prognosis. Antibodies reactive with neuronal voltage-gated potassium channels (VGKCs) are recently recognized as a pathogenic cause in nonparaneoplastic limbic encephalitis, which is responsive to immunotherapy. We report a patient who had subacute encephalopathy with clinical and radiographic evidences of limbic encephalitis. The patient was seropositive for VGKC antibodies and resulted in a good prognosis with steroids. This has not yet been reported in Korea.
Antibodies ; Humans ; Immunotherapy ; Korea ; Limbic Encephalitis* ; Neurons ; Potassium Channels, Voltage-Gated* ; Prognosis ; Steroids