When does facial synkinesis develop?

The objective of this study is to clarify when facial palsy patients with lower value of Electroneurography (ENoG) should begin the rehabilitation to prevent the development of facial synkinesis. For this purpose, we examined the relationship between the value of ENoG measured 10-14 days after facial palsy onset and the onset day of the development of oral-ocular synkinesis. Sixteen patients with facial palsy including 11 with Bell’s palsy and 5 with Ramsay Hunt syndrome (7 men and 9 women ; 15-73 years old ; mean age, 41.6 years) were enrolled in this study. There was no correlation between ENoG value and the onset day of the development of oral-ocular synkinesis (ρ = .09, p = .73). Oral-ocular synkinesis began to develop in 4.0 ± 0.7 months (mean ± SD ; range : 3.1-5.0 months) after facial palsy onset regardless of ENoG value. In conclusion, ENoG value cannot predict when facial synkinesis develops in patients with facial palsy. We recommend that facial palsy patients with a high risk for the development of synkinesis begin the biofeedback rehabilitation with mirror to prevent the development of facial synkinesis 3 months after facial palsy onset

Early Maternal and Social Deprivation Expands Neural Stem Cell Population Size and Reduces Hippocampus/Amygdala-Dependent Fear Memory.

Early life stress can exert detrimental or beneficial effects on neural development and postnatal behavior depending on the timing, duration, strength, and ability to control the stressors. In this study, we utilized a maternal and social deprivation (MSD) model to investigate the effects of early life stress on neural stem cells (NSCs) and neurogenesis in the adult brain. We found that MSD during the stress-hyporesponsive period (SHRP) (early-MSD), when corticosterone secretion is suppressed, increased the size of the NSC population, whereas the same stress beyond the SHRP abrogated these effects. Early-MSD enhanced neurogenesis not only in the dentate gyrus of the hippocampus, one of the classic neurogenic regions, but also in the amygdala. In addition, mice exposed to early-MSD exhibited a reduction in amygdala/hippocampus-dependent fear memory. These results suggest that animals exposed to early life stress during the SHRP have reinforced stress resilience to cope with perceived stressors to maintain a normal homeostatic state

顔面神経麻痺患者の静的顔面非対称の後遺症に対する3次元スキャン解析を用いた新規評価法

Objective: During the process of neural recovery after facial palsy, distressing sequelae of static and dynamic facial asymmetry develop in patients with facial palsy. A pronounced nasolabial fold is mainly responsible for static facial asymmetry, which leads to many psychological and social problems in patients. Objective and qualitative assessment of facial appearance is critical to determine the severity of sequelae of static facial asymmetry and whether an intervention is effective for treatment. In the present study, an attempt was made to develop three-dimensional analysis method to assess sequelae of static facial asymmetry after facial palsy. Methods: Eight patients with sequelae of facial asymmetry after facial palsy and ten healthy volunteers were enrolled. We used three-dimensional scanning analysis with a portable non-contact optical scanner to obtain three-dimensional surface data from a patient's face and produced a three-dimensional digital model of the face. We then identified a reference plane fixed with the patient's face, and measured the depth of the nasolabial fold of the face. Results: The nasolabial fold of the face on the affected side was significantly deeper than that on the unaffected side in patients with sequelae of static facial asymmetry after facial palsy. However, the depth of the facial nasolabial fold on the right side was not different from that on the left side in healthy volunteers. Affected-unaffected side differences in the depth of the nasolabial fold in patients with sequelae of static facial asymmetry after facial palsy were significantly larger than left-right differences in the depth of the nasolabial fold in healthy volunteers. Two weeks after treatment with botulinum toxin injection to the affected zygomaticus muscles, affected-unaffected side differences in the depth of the nasolabial fold were significantly decreased in the patients. In the patients who received botulinum toxin, the absolute values of affected-unaffected side differences in the depth of the nasolabial fold measured using the three-dimensional scanning analysis showed a significant positive correlation with the visual analog scale scores of facial asymmetry marked by independent doctors. Conclusion: The present findings suggest that affected-unaffected side differences in the depth of the nasolabial fold of the measured using three-dimensional scanning analysis can be used as an index of sequelae of static facial asymmetry. It is also suggested that the index can evaluate whether interventions are effective for the treatment of sequelae

Synthesis and characterization of 11C-labeled benzyl amidine derivatives as PET radioligands for GluN2B subunit of the NMDA receptors

GluN2B-containing NMDA receptors (NMDARs) play fundamental roles in learning and memory, although they are also associated with various brain disorders. In this study, we synthesized and evaluated three 11 C-labeled N-benzyl amidine derivatives 2-[11 C]methoxybenzyl) cinnamamidine ([11 C]CBA), N-(2-[11 C]methoxybenzyl)-2- naphthamidine ([11 C]NBA) and N-(2-[11 C]methoxybenzyl)quinoline-3-carboxamidine ([11 C]QBA) as PET radioligands for these receptors. The 11 C-benzyl amidines were synthesized via conventional methylation of corresponding des-methyl precursors with [11 C]CH3 I. In vitro binding characteristics were examined in brain sagittal sections using various GluN2B modulators and off-target ligands. Further, in vivo brain distribution studies were performed in normal mice. The 11 C-labeled benzyl amidines showed high specific binding to the GluN2B subunit at in vitro. In particular, the quinoline derivative [11 C] QBA had the best binding properties in terms of high brain localization to GluN2B-rich regions and specificity to the GluN2B subunit. Conversely, these 11 C-radioligands showed the brain distributions were inconsistent with GluN2B expression in biodistribution experiments. The majority of the radiolabeled compounds were identified as metabolized forms, of which amido derivatives seemed to be the major species. Although these 11 C-ligands had high specific binding to the GluN2B subunit, significant improvement in metabolic stability is necessary for successful PET imaging of the GluN2B subunit of NMDARs

Difference in brain distribustions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel

High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[11C]methoxyphenyl)-2(1H)-quinolone ([11C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-d-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[11C]4HQ (5Et-[11C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[11C]4HQ (5I-[11C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[11C]4HQ and 5I-[11C]4HQ was quite similar to that previously observed between [11C]L-703,717 and [11C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these 11C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[11C]4HQ at 1 min after intravenous injections were comparable to that of [11C]4HQ, but they were 1.3-2.1 times higher than that of [11C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [11C]4HQ and 5Et-[11C]4HQ in contrast to [11C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[11C]4HQ (16-36% inhibition) but not that of 5I-[11C]4HQ. In this study, it was found that a small structural change in [11C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [11C]4-hydroxyquinolones on the NMDA ion channel - agonist-sensitive and agonist-insensitive (or antagonist-preferring) sites