Near-infrared spectroscopy has been used for measurement of changes in cerebral Hb concentrations in infants to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved spectroscopy (TRS) were performed in 22 neonates to estimate the values of light absorption coefficient and reduced scattering coefficient (' s ), cerebral Hb oxygen saturation (ScO 2 ), cerebral blood volume (CBV), and differential pathlength factor (DPF), and the relationships between postconceptional age and ' s , ScO 2 , CBV, and DPF were investigated. A portable three-wavelength TRS system with a probe attached to the head of the neonate was used. The mean ' s values at 761, 795, and 835 nm in neonates were estimated to be (mean Ϯ SD) 6.46 Ϯ 1.21, 5.90 Ϯ 1.15 and 6.40 Ϯ 1.16/cm, respectively. There was a significant positive relationship between postconceptional age and ' s at those three wavelengths. The mean ScO 2 value was calculated to be 70.0 Ϯ 4.6%, and postconceptional age and ScO 2 showed a negative linear relationship. The mean value of CBV was 2.31 Ϯ 0.56 mL/100 g. There was a significant positive relationship between postconceptional age and CBV. During the perinatal period, the brain undergoes anatomic, functional, and metabolic changes. The anatomic changes include neuronal proliferation, migration, organization, and myelination, and the metabolic changes match the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. Noninvasive assessment of cerebral anatomic changes and of oxygen delivery and utilization is useful for evaluating the effectiveness of therapy and for preventing oxygen toxicity in seriously ill neonates.Near-infrared spectroscopy (NIRS) has been used in the clinical field with various measuring devices using several wavelengths. A method using continuous-wave NIRS has been developed and reported to be suitable for clinical use in infants (1-7). However, current commercially available NIRS systems can detect only changes in cerebral Hb. Because NIRS is based on the modified Beer-Lambert law, a change in hematocrit and blood volume as well as developmental and pathophysiologic changes in brain tissue affect the pathlength of near-infrared light. In a few recent studies, absolute values of cerebral Hb oxygen saturation (ScO 2 ) and cerebral blood volume (CBV) in infants were measured without inducing Hb concentration changes by using full-spectral near-infrared spectroscopy (8 -11) and spatially resolved spectroscopy (12). However, these

During the developmental stage, the brain undergoes anatomic, functional, and metabolic changes necessary to support the complex adaptive behavior of a mature individual. Estimation of developmental changes occurring in different regions of the brain would provide a means of relating various behavioral phenomena to maturation-specific brain structures, thereby providing useful information on structure-function relationships in both normal and disease states. We used multichannel near-infrared spectroscopy (MNIRS), a new noninvasive imaging technique for revealing the course of neural activity in selected brain regions, to monitor the activities of the visual cortex as mirrored by hemodynamic responses in infants subjected to photostimulation during natural sleep. In the infants, oxyhemoglobin and total hemoglobin decreased and deoxyhemoglobin increased in the visual cortex with photostimulation. This pattern of responses was different from the response pattern in adults reported previously. The different patterns of responses to photostimulation in the visual cortices of infants and adults might reflect developmental and behavioral differences. It may reflect a different functional organization of the visual cortex in infants or ongoing retinal development. Our results demonstrated that regional hemodynamic change could be detected in a small area around the visual cortex. MNIRS offers considerable potential for research and noninvasive clinical applications. Hum. Brain Mapp. 22:122-132, 2004.

The blood-brain barrier (BBB) not only impedes the influx of intravascular substances from blood to brain, but also promotes transport of substances from blood to brain or from brain to blood through several transport systems such as carrier-mediated transport, active efflux transport, and receptor-mediated transport systems. The multidrug resistance transporter P-glycoprotein (P-gp) is an ATP-dependent efflux pump and contributes to efflux of undesirable substances such as amyloid-beta:(Abeta) proteins from the brain into the blood as well as many drugs such as anti-cancer drugs. The inhibition of P-gp has favorable and unfavorable effects on living bodies. P-gp deficiency at the BBB induces the increase of Abeta:deposition in the brain of an Alzheimer disease mouse model. It is also known that the Abeta:deposition is inversely correlated with P-gp expression in the brains of elderly non-demented humans. However, the transient inhibition of P-gp by antidepressants enables medicines such as anti-cancer drugs to enter the brain. Concerning Abeta:clearance in the brain, the low-density lipoprotein receptor-related protein 1 (LRP1) is a major efflux transporter for Abeta, while the receptor for advanced glycation end products (RAGE) is a major influx transporter for Abeta:across the BBB. Dysfunction of the BBB with efflux and influx transporters may contribute to the pathogenesis of some degenerative neuronal disorders. This review will focus on several transporters and discuss how medicines pass the BBB to reach the brain parenchyma.

Near-infrared spectroscopy (NIRS) has been used for measurement of cerebral hemoglobin (Hb) concentrations in neonates to study cerebral oxygenation and hemodynamics. We perform measurements by portable three-wavelength NIR time-resolved spectroscopy (TRS) in a piglet hypoxia model with various degrees of oxygenation to estimate the absorption coefficient (mu(a)) and reduced scattering coefficient (mu(s)') of the head. Measurements of absolute values of mu(a) at three wavelengths enable estimation of Hb concentration and Hb oxygen saturation in the head (SO2). However, there is a problem concerning which background absorption should be used to estimate Hb concentration in the head derived from mu(a) at three wavelengths because it is different from a simple in vitro model. Therefore, we use two different background absorption values with the assumption that background absorption is due only to 85% (by volume) water or that background absorption is equal to absorption of the piglet head with blood exchange transfusion by fluorocarbon (FC), and we compared SO2 measured by TRS with arterial Hb oxygen saturation (SaO2) and sagittal sinus venous Hb oxygen saturation (SvO2) measured by a co-oximeter at several inspired fractional O2(FI(O2)) concentrations. We find that SO2 values using the absorption (abs) of the piglet head with blood exchange transfusion (BET) by FC are not significantly different from SO2 values using the water-only background at FI(O2) in the range of 15 to 100%, but that the values using abs of the head with BET by FC are lower than the values using the water-only background at FI(O2) in the range of 12 to 4%. The SO2 values calculated from the water-only background are higher than those of SaO2 at FI(O2) in the range of 10 to 4%. However, SO2 values using the abs of the head with BET by FC are between those of SaO2 and SvO2 over the whole range of FI(O2). Therefore, abs of the head with BET by FC is more useful for estimation of the absolute values of oxyHb and deoxyHb of the piglet head.

The purpose of this study was to investigate the effects of whole body vibration (WBV) on oxygenation of vastus lateralis muscle during squatting exercise. Eighteen male subjects [mean age, 27.3 +/- 6.0 (SD) years; mean height, 171.8 +/- 4.9 cm; mean weight, 64.4 +/- 6.1 kg] performed squatting exercise on a vibration platform for 3 min with and without vibration, and changes in oxygenation of the vastus lateralis muscle were determined by near-infrared spectroscopy. The muscle oxygenation levels and total haemoglobin and myoglobin levels (total Hb/Mb) decreased during squatting exercise with and without vibration. After exercise, the muscle oxygenation level and total Hb/Mb rapidly increased from the minimum value during exercise and remained constant for latter 10 min. The muscle oxygenation levels with vibration from 90 to 180 s after the start of squatting exercise were significantly lower than those without vibration. Total Hb/Mb with vibration from 90 s after the squatting exercise to 540 s were significantly higher than those without vibration. This study demonstrated that WBV exercise affects the oxygenation level of vastus lateralis muscle and reduces muscle oxygenation level compared to that with no WBV. Therefore, WBV exercise may be an efficient training stimulus for muscle deoxygenation.

Early life stress interrupts brain development through the disturbance of various neurotransmitter and neurotrophic factor activities, but the details remain unclear. In the current study, we focused on the serotonergic system, which plays a critical role in brain development, and examined the time-dependent influence of prolonged maternal separation on male Sprague-Dawley rats. The rats were separated from their dams for 3h twice-daily during postnatal days (PDs) 2-20. The influence of prolonged maternal separation was analyzed on PDs 7, 14, 21, and 28 using HPLC to assess concentrations of serotonin and 5-hydroxyindoleacetic acid and using real-time RT-PCR to measure mRNA expression of the serotonin 1A and 2A receptors in various brain regions. HPLC revealed imbalance between serotonin and 5-hydroxyindoleacetic acid in midbrain raphe nuclei, the amygdala, the hippocampus, and the medial prefrontal cortex (mPFC) on PDs 7 and 14. Furthermore, real-time RT-PCR showed attenuation of mRNA expression of the serotonin 1A receptor in the hippocampus and the mPFC and of the serotonin 2A receptor only in the mPFC on PDs 7 and 14. The observed alterations returned to control levels after maternal separation ended. These findings suggest that the early life stress of prolonged maternal separation disturbs the serotonergic system during a crucial period of brain development, which might in part be responsible for emotional abnormalities later in life.

Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood.

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