Coupling of capillary RBC flow failure with neuronal depolarization

RBC (oxygen-carrier) behaviour in the cerebrocortical microvasculature during K^+^-induced cortical spreading depression (CSD) was examined in urethane-anesthetized male Wistar rats (n=10). The movements of FITC-labeled RBCs in single capillaries in the cortical region were traced with a high-speed camera laser scanning confocal fluorescence microscope and analyzed with Matlab domain software, KEIO-IS2, to obtain the velocities of all labeled RBCs appearing in local capillaries during CSD wave propagation. We found that CSD induced periodic decreases in both RBC number and velocity until RBCs halted or disappeared for 3.3 +/- 2.3 s, and then RBC flow was restored. The RBC flow stall was statistically significant (P < 0.05). During capillary flow failure in association with CSD spread, systemic arterial blood pressure remained unchanged. We conclude that RBCs are transiently sieved and stalled in capillaries during neuronal depolarization, and we suggest that this neuro-capillary coupling involves a hemorheological (viscosity-related) mechanism

Depolarization increases cellular light transmission

Application of optical methods to human brain tissue in vivo, e.g., measuring oxyhemoglobin and deoxyhemoglobin concentration changes with near-infrared spectroscopy (NIRS), requires the a priori assumption that background optical properties remain unchanged during measurements1,2. However, fundamental knowledge about light scattering by brain cells per se remains sparse; many factors influence light transmission changes through living brain tissue, bringing into question what is being measured. We have observed slow wave-ring spreads of light transmission changes on the rat cerebral cortex during potassium-induced cortical spreading depression (CSD) and ascribed them to squeezing-out of blood from capillaries by swollen brain cells3,4. However, in rat hippocampal slices, where no blood components were involved, similar light transmission changes were observed during K+-induced CSD and ascribed to cell swelling and dendritic beading5,6,7. Here we show that two-dimensional light scattering changes occur through suspensions of osmotically swollen (depolarized) red blood cells, apparently arising from light scattering changes at the less curved, swollen surface of the steep electrochemical gradient coupled with water activity difference across the plasmic membrane. These optical property changes are likely to be relevant to interpretation of photometry or spectroscopy findings of brain tissue in vivo, where neurons are polarizing and depolarizing during brain function

Headache Associated with Myasthenia Gravis: The Impact of Mild Ocular Symptoms

Myasthenia gravis (MG) patients visiting outpatient clinics frequently complain of headache. However, there have been few reports on the relation between chronic headache and myasthenia gravis (MG). We aimed to investigate whether MG symptoms affect the development or worsening of chronic headache. Among the 184 MG patients who were followed at the MG clinics, tension-type headache was observed in 71 (38.6%) patients and 9 (4.9%) complained of migraine. Twenty-five (13.6%) complained that headache appeared or was exacerbated after the MG onset. The investigation into differences in the clinical characteristics of the MG patients showed that women tended to suffer from MG-associated headache more often than men. Logistic regression analyses revealed that female gender and mild ocular symptoms were independently predictive of headache associated with MG. Our results suggest that treatment of chronic headache should be required to improve the quality of life in MG patients

Interactions between migraine and tension-type headache and alcohol drinking, alcohol flushing, and hangover in Japanese

The aim of the study was to investigate associations between headache types and alcohol drinking, alcohol flushing, and hangover. Alcohol consumption is inhibited by the presence of inactive aldehyde dehydrogenase-2 (ALDH2) whose carriers are susceptible to alcohol flushing and hangovers. We conducted a cross-sectional study of the 2,577 subjects (men/women: 1,018/1,559) who reported having ever experienced headaches unrelated to common colds and alcohol hangovers among 5,408 (2,778/2,630) Tokyo health checkup examinees. We used a questionnaire inquiring about current and past facial flushing after drinking a glass of beer which identifies the presence of inactive ALDH2 with a sensitivity and specificity of approximately 90%. Based on ICHD-II criteria migraine was diagnosed in 419 (75/344) subjects, and tension-type headache (TTH) in 613 (249/364). We classified the headaches of the remaining 1,545 (694/851) of headaches sufferers into the category “other headaches (OH)”. The migraineurs drank alcohol less frequently than the subjects with TTH among current/past alcohol flushers and than the subjects with OH regardless of flushing category. No such difference in drinking frequency was observed between TTH and OH. Current/past flushers drank alcohol less frequently than never flushers, and the likelihood that male migraineurs would avoid alcohol drinking than men with TTH or OH was stronger among current/past flushers than among never flushers. Flushers and women were more susceptible to hangover than never flushers and men, respectively, regardless of headache type. Among never flushers, women with migraine were more susceptible to hangover than women with OH. The difference in alcohol sensitivity may partly explain less alcohol consumption by migraineurs

Assessment of Melanoma-Initiating Cell Markers and Conventional Parameters in Sentinel Lymph Nodes of Malignant Melanoma

Sentinel lymph node (SLN) biopsies have widely been used for the detection of occult LN metastasis of malignant melanoma (MM). In addition to conventional biomarkers, we assessed the diagnostic and prognostic significance of melanoma-initiating cell (MIC) markers in SLNs of MM. We examined the expressions of gp100, MART-1 and tyrosinase mRNA for routine diagnosis and those of ABCB5, CD133, nestin, KDM5B, NGFR and RANK mRNA as MIC markers. The presence of micrometastasis was confirmed immunohistochemically using antibodies to S-100, HMB-45, MART-1, and tyrosinase. Discordance between immunohistochemical and molecular data was observed in 14 of 70 (20.0%) patients, among whom five (7.1%) were positive for only molecular markers;two of these five patients tested positive for micrometastasis by repeated immunohistochemical stainings. The quantitative expression levels of gp100, MART-1, and tyrosinase mRNA were significantly higher in the metastatic LNs;the cut-off values remain to be elucidated. ABCB5 mRNA expression was detected more frequently in the metastatic SLNs (p＜0.05) and in the group of patients with recurrence. To make a definite diagnosis of metastasis, we still need a combination of immunohistochemical and molecular probes. ABCB5 might be a suitable molecular marker for the detection of melanoma-initiating cells in SLNs