Relationship Between Brain Activity and Real-Road Driving Behavior: A Vector-Based Whole-Brain Functional Near-Infrared Spectroscopy Study

Automobile driving requires multiple brain functions. However, the brain regions related to driving behavior are unknown. Therefore, we measured activity of the frontal, parietal and occipital lobes during driving using functional near-infrared spectroscopy (fNIRS). Cortical activation patterns were examined in relation to driving behaviors, such as steering motion, accelerator pedal motion, and speed control. Six healthy adults participated in the experiment. Cerebral oxygen exchange (COE) was calculated based on the oxyhemoglobin and deoxyhemoglobin concentrations measured by fNIRS. The COE and driving behavior data were collected every 1 m and averaged for all subjects. Functional NIRS data for all 98 channels were extracted using principal component analysis. Similarity between extracted components and driving behaviors were confirmed by |cosine similarity|\u3e0.3. Among the factors with confirmed similarity, we identified brain regions with high principal component loading (|PCL|\u3e0.4). Among the 16 COE factors extracted, COE factor 1 and factor 5 exhibited similarity with steering motion (cosine similarity: factor 1, -0.538; factor 5, 0.551). The PCLs of COE factor 1 and factor 5 were high in the frontal lobe (Brodmann areas [BAs] 9, 8, and 4/3) (PCL\u3e0.8). COE factor 6 exhibited a similarity with accelerator pedal motion (cosine similarity: 0.369), and the PCL of COE factor 6 was highest in the parietal lobe (BA7) (PCL= -0.62). Speed control did not exhibit similarity with any COE factor. These findings will contribute to the selection of brain measurement areas when fNIRS is used for vehicle driving assessment

Flt1/VEGFR1 heterozygosity causes transient embryonic edema

Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1+/−) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1+/− capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1+/− embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1−/− mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1+/−; Aspp1−/− mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype

In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of severe pneumococcal pneumonia.

KRP-109 is a novel specific inhibitor of neutrophil elastase (NE). Various studies suggest that NE inhibitors reduce lung injury associated with systemic inflammatory response syndrome (SIRS). In this study, the efficacy of KRP-109 was examined using a murine model of severe pneumonia induced by Streptococcus pneumoniae (S. pneumoniae). Female mice (CBA/J, aged 5 weeks) were inoculated intranasally with penicillin-susceptible S. pneumoniae (ATCC49619 strain, 2.5 × 10(8) CFU/mouse). KRP-109 (30 or 50 mg/kg) or physiological saline as a control was administered intraperitoneally every 8 h beginning at 8 h after inoculation, and survival rate was evaluated over 7 days. Histopathological and bacteriological analyses of the lung, and bronchoalveolar lavage were performed at 48 h post-infection. The mice treated with KRP-109 (KRP-109 mice) tended to have higher survival rate than those given saline. The lung tissues of the KRP-109 mice had few neutrophils in the alveolar walls and less inflammation. Furthermore, KRP-109 decreased significantly total cell and neutrophil counts, and cytokine levels (interleukin 1β and macrophage inflammatory protein 2) in bronchoalveolar lavage fluid. Viable bacterial numbers in lung were not influenced by treatment of KRP-109. The present results indicate that KRP-109 reduces lung inflammation in a murine model, and that KRP-109 may be useful for the treatment of patients with severe pneumonia