Photo finish: A polymeric micelle system is formed in aqueous media by electrostatic assembly of an anionic dendrimeric porphyrin and a poly(ethylene glycol)–poly(L‐lysine) block copolymer (see picture). The micelles exhibit high photocytotoxicity and stability. The hydrodynamic size (ca. 60 nm) makes this polymeric micelle system suitable for intravenous administration in photodynamic tumor therapy.

Our data suggest that NIR laser irradiation is a promising experimental and therapeutic tool in the field of cerebral circulation research.

No abstract

Despite many efforts, the pathophysiology and mechanism of blast-induced traumatic brain injury (bTBI) have not yet been elucidated, partially due to the difficulty of real-time diagnosis and extremely complex factors determining the outcome. In this study, we topically applied a laser-induced shock wave (LISW) to the rat brain through the skull, for which real-time measurements of optical diffuse reflectance and electroencephalogram (EEG) were performed. Even under conditions showing no clear changes in systemic physiological parameters, the brain showed a drastic light scattering change accompanied by EEG suppression, which indicated the occurrence of spreading depression, long-lasting hypoxemia and signal change indicating mitochondrial energy impairment. Under the standard LISW conditions examined, hemorrhage and contusion were not apparent in the cortex. To investigate events associated with spreading depression, measurement of direct current (DC) potential, light scattering imaging and stereomicroscopic observation of blood vessels were also conducted for the brain. After LISW application, we observed a distinct negative shift in the DC potential, which temporally coincided with the transit of a light scattering wave, showing the occurrence of spreading depolarization and concomitant change in light scattering. Blood vessels in the brain surface initially showed vasodilatation for 3–4 min, which was followed by long-lasting vasoconstriction, corresponding to hypoxemia. Computer simulation based on the inverse Monte Carlo method showed that hemoglobin oxygen saturation declined to as low as ∼35% in the long-term hypoxemic phase. Overall, we found that topical application of a shock wave to the brain caused spreading depolarization/depression and prolonged severe hypoxemia-oligemia, which might lead to pathological conditions in the brain. Although further study is needed, our findings suggest that spreading depolarization/depression is one of the key events determining the outcome in bTBI. Furthermore, a rat exposed to an LISW(s) can be a reliable laboratory animal model for blast injury research.

The ear is the organ that is most sensitive to blast overpressure, and ear damage is most frequently seen after blast exposure. Blast overpressure to the ear results in sensorineural hearing loss, which is untreatable and is often associated with a decline in the quality of life. In this study, we used a rat model to demonstrate the pathophysiological and structural changes in the inner ear that replicate pure sensorineural hearing loss associated with blast injury using laser-induced shock wave (LISW) without any conductive hearing loss. Our results indicate that threshold elevation of the auditory brainstem response (ABR) after blast exposure was primarily caused by outer hair cell dysfunction induced by stereociliary bundle disruption. The bundle disruption pattern was unique; disturbed stereocilia were mostly observed in the outermost row, whereas those in the inner and middle rows stereocilia remained intact. In addition, the ABR examination showed a reduction in wave I amplitude without elevation of the threshold in the lower energy exposure group. This phenomenon was caused by loss of the synaptic ribbon. This type of hearing dysfunction has recently been described as hidden hearing loss caused by cochlear neuropathy, which is associated with tinnitus or hyperacusis.

Diagnosis of burn depths is crucial to determine the treatment plan for severe burn patients. However, an objective method for burn depth assessment has yet to be established, although a commercial laser Doppler imaging (LDI) system is used limitedly. We previously proposed burn depth assessment based on photoacoustic imaging (PAI), in which thermoelastic waves originating from blood under the burned tissue are detected, and we showed the validity of the method by experiments using rat models with three different burn depths: superficial dermal burn, deep dermal burn and deep burn. On the basis of those results, we recently developed a real-time PAI system for clinical burn diagnosis. Before starting a clinical trial, however, there is a need to reveal more detailed diagnostic characteristics, such as linearity and error, of the PAI system as well as to compare its characteristics with those of an LDI system. In this study, we prepared rat models with burns induced at six different temperatures from 70 to 98 8C, which showed a linear dependence of injury depth on the temperature. Using these models, we examined correlations of signals obtained by PAI and LDI with histologically determined injury depths and burn induction temperatures at 48 hours postburn. We found that the burn depths indicated by PAI were highly correlative with histologically determined injury depths (depths of viable vessels) as well as with burn induction temperatures. Perfusion values measured by LDI were less correlative with these parameters, especially for burns induced at higher temperatures, being attributable to the limited detectable depth for light involving a Doppler shift in tissue. In addition, the measurement errors in PAI were smaller than those in LDI. On the basis of these results, we will be able to start clinical studies using the present PAI system.

Abstract.A light-scattering signal, which is sensitive to cellular/subcellular structural integrity, is a potential indicator of brain tissue viability because metabolic energy is used in part to maintain the structure of cells. We previously observed a unique triphasic scattering change (TSC) at a certain time after oxygen/glucose deprivation for blood-free rat brains; TSC almost coincided with the cerebral adenosine triphosphate (ATP) depletion. We examine whether such TSC can be observed in the presence of blood in vivo, for which transcranial diffuse reflectance measurement is performed for rat brains during hypoxia induced by nitrogen gas inhalation. At a certain time after hypoxia, diffuse reflectance intensity in the near-infrared region changes in three phases, which is shown by spectroscopic analysis to be due to scattering change in the tissue. During hypoxia, rats are reoxygenated at various time points. When the oxygen supply is started before TSC, all rats survive, whereas no rats survive when the oxygen supply is started after TSC. Survival is probabilistic when the oxygen supply is started during TSC, indicating that the period of TSC can be regarded as a critical time zone for rescuing the brain. The results demonstrate that light scattering signal can be an indicator of brain tissue reversibility. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

A series of poly(benzyl ether) dendrimer porphyrins (DPs) (Gn ) n-generation dendrimer, n ) 1-3) was examined as potential photosensitizers for photodynamic therapy (PDT). Polyion complexes (PICs) between the DPs and poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) were formed via an electrostatic interaction between the positively charged poly(L-lysine) (PLL) segment and negatively charged periphery of the DPs. Dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM) showed that G3 formed a core-shell-type nanocarrier micelle, whereas G1 and G2 formed irregular-shaped nanoparticles with a relatively high polydispersity. The photophysical properties of the DP-loaded PIC nanocarriers strongly depend on the generation of the DPs. In the case of G1 and G2, their fluorescence lifetime and oxygen consumption ability were significantly reduced by the formation of the PIC nanocarriers, whereas the G3-loaded PIC nanocarrier exhibited almost comparable fluorescence lifetimes and oxygen consumption abilities to the free G3. The incorporation of DPs into PIC nanocarriers resulted in an appreciable increase in the cellular uptake, yet inversely correlated with the generation. Alternatively, the photocytotoxicity of the DPs within the nanocarriers increased with an increase in the generation despite a decrease in the cellular uptake. By correlating the effects of the uptake amount with the photocytotoxicity, the PIC nanocarriers showed remarkable enhancement of the PDT efficacy dependent on the generation of DPs.