Ok Kyu Park

High-resolution three-photon biomedical imaging using doped ZnS nanocrystals

Three-photon excitation is a process that occurs when three photons are simultaneously absorbed within a luminophore for photo-excitation through virtual states. Although the imaging application of this process was proposed decades ago, three-photon biomedical imaging has not been realized yet owing to its intrinsic low quantum efficiency. We herein report on high-resolution in vitro and in vivo imaging by combining three-photon excitation of ZnS nanocrystals and visible emission from Mn(2+) dopants. The large three-photon cross-section of the nanocrystals enabled targeted cellular imaging under high spatial resolution, approaching the theoretical limit of three-photon excitation. Owing to the enhanced Stokes shift achieved through nanocrystal doping, the three-photon process was successfully applied to high-resolution in vivo tumour-targeted imaging. Furthermore, the biocompatibility of ZnS nanocrystals offers great potential for clinical applications of three-photon imaging.

Cephalopod‐Inspired Miniaturized Suction Cups for Smart Medical Skin

M. K. Choi, C. Choi, J. Kim, D. J. Lee, M. Kim, W. Hyun, S. J. Kim, Prof. T. Hyeon, Prof. D.-H. Kim Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 151-742 , Republic of Korea E-mail: dkim98@snu.ac.kr M. K. Choi, C. Choi, J. Kim, D. J. Lee, M. Kim, W. Hyun, S. J. Kim, Prof. T. Hyeon, Prof. D.-H. Kim School of Chemical and Biological Engineering Institute of Chemical Processes Seoul National University Seoul 151-742 , Republic of Korea O. K. Park, S.-H. Kwon Division of Bio-imaging Korea Basic Science Institute Chun-Cheon 200-701 , Republic of Korea S. Qiao, Prof. N. Lu Center for Mechanics of Solids Structures and Materials Department of Aerospace Engineering and Engineering Mechanics Texas Materials Institute University of Texas at Austin 210 E 24th St , Austin, TX 78712 , USA R. Ghaffari MC10 Inc. 9 Camp St , Cambridge , MA 02140 , USA H. J. Hwang Division of Cardiology Beth Israel Deaconess Medical Center Harvard Medical School , Boston , MA 02215 , USA

Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus.

Tryptophan‐derived indole compounds have been widely investigated as antioxidants and as free‐radical scavengers. Indole‐3‐propionic acid (IPA), one of these compounds, is a deamination product of tryptophan. In the present study, we used Mongolian gerbils to investigate IPAs neuroprotective effects against ischemic damage and its antioxidative effects in the hippocampal CA1 region (CA1) after 5 min of transient forebrain ischemia. The repeated oral administration of IPA (10 mg/kg) for 15 days before ischemic surgery protected neurons from ischemic damage. In this group, the percentage of cresyl violet–positive neurons in the CA1 was 56.8% compared with that in the sham group. In the vehicle‐treated group, glial fibrillary acidic protein (GFAP)‐, S‐100‐, and vimentin‐immunoreactive astrocytes and ionized calcium‐binding adapter molecule 1 (Iba‐1)– and isolectin B4 (IB4)–immunoreactive microglia were activated 4 days after ischemia/reperfusion, whereas in the IPA‐treated ischemic group, GFAP, S‐100, Iba‐1, and IB4, but not vimentin, immunoreactivity was distinctly lower than that in the vehicle‐treated ischemic groups. The administration of IPA significantly decreased the level of 4‐hydroxy‐2‐nonenal, a marker of lipid peroxidation, in ischemic hippocampal homogenates compared with that in the vehicle‐treated ischemic groups at various times after ischemia/reperfusion. In addition, immunostaining for 8‐hydroxy‐2′‐deoxyguanosine showed DNA damage in pyramidal neurons in the ischemic CA1 was significantly lower in the IPA‐treated ischemic groups than in the vehicle‐treated ischemic groups. These results suggest that IPA protects neurons from ischemia‐induced neuronal damage by reducing DNA damage and lipid peroxidation.

Melatonin's Protective Action Against Ischemic Neuronal Damage Is Associated With Up-Regulation of the MT2 Melatonin Receptor

Melatonin is a potent free radical scavenger and antioxidant and has protective effects against ischemic damage. In the present study, we examined the relationship between the neuroprotective effects of melatonin and the activation of MT2 melatonin receptor in the hippocampal CA1 region (CA1) after transient cerebral ischemia. MT2 immunoreactivity and protein levels were increased in the CA1 after ischemic damage. Most of MT2‐immunoreactive cells were colocalized with astrocytes, not microglia, in the ischemic CA1. In the melatonin‐sham group, MT2 immunoreaction and protein levels were increased compared with the sham group, and MT2 immunoreactivity and its protein levels in the melatonin‐ischemia group were similar to those in the melatonin‐sham group. In addition, melatonin treatment attenuated the activation of astrocytes and microglia. These results indicate that MT2 are increased and expressed in astrocytes in the ischemic region after an ischemic insult. The activation of MT2 melatonin receptor in the CA1 after melatonin treatment may be involved in the neuroprotective effect associated with melatonin after ischemic injury.

Neuronal damage is much delayed and microgliosis is more severe in the aged hippocampus induced by transient cerebral ischemia compared to the adult hippocampus

Activation of astrocytes and microglia in the post-ischemic hippocampus has been investigated using ischemia models. The aim of this study was to investigate differences of delayed neuronal death and gliosis in the hippocampal CA1 region (CA1) between adult and aged gerbils. Delayed neuronal death in the CA1 was later in the aged gerbil than in the adult gerbil after ischemia/reperfusion (I/R). GFAP-immunoreactive ((+)) astrocytes and Iba-1(+) microglia were activated following neuronal damage in both adult and aged gerbils after I/R. Changes in GFAP immunoreactivity and protein levels were similar in both groups: they were distinctly increased from 3 days after I/R. Iba-1 immunoreactivity and protein levels in the aged sham gerbil were much higher than those in the adult sham gerbil. Activation of microglia in the CA1 of the aged group was slower, lower 4 days and much higher 7 days than that in the adult gerbil after I/R. These observations indicate that delayed neuronal death in the CA1 of the aged group is slower than that in the adult group after I/R. In addition, microglial activation, not astrocytes, in the aged ischemia group is slower and more intense than that in the adult ischemia group.

Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide.

Lipopolysaccharide (LPS) induces a strong immune response, and pretreatment with low dose of LPS suppresses the production of proinflammatory mediators. In the present study, we investigated the effect of LPS preconditioning on the delayed neuronal death in the gerbil hippocampal CA1 region after 5 min of transient cerebral ischemia. LPS preconditioning showed neuroprotective effects against ischemic damage in the hippocampal CA1 region after ischemic insult: about 92% of neurons in the CA1 region survived in the LPS-treated ischemia group. LPS preconditioning maintained anti-inflammatory cytokines, such as interleukin (IL)-4 and IL-13, in pyramidal neurons in the CA1 region after ischemia/reperfusion. In addition, IL-4 and IL-13 protein levels in the CA1 region of the LPS-treated ischemia group were similar to the vehicle-treated sham group. We found that reactive gliosis was markedly attenuated in the CA1 region of the LPS-treated ischemia group compared to the vehicle-treated ischemia group using immunohistochemistry of glial fibrillary acidic protein for astrocytes, and ionized calcium-binding adapter molecule 1 and isolectin B4 for microglia. These results indicate that LPS preconditioning may provide neuroprotection in the ischemic hippocampal CA1 region via maintenance of anti-inflammatory cytokines and suppression of glial activation.

A novel near-infrared fluorescence chemosensor for copper ion detection using click ligation and energy transfer

A novel near-infrared fluorescence (NIRF) copper sensor allows rapid and ultra-sensitive detection of copper ions with excellent selectivity and specificity due to the specificity of click ligation and effective dark-quenching mechanism.

Neuroprotection of ebselen against ischemia/reperfusion injury involves GABA shunt enzymes

Seleno-organic compound, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), is a substrate with radical-scavenging activity. In this study, we observed the neuroprotective effects of ebselen against ischemic damage and on GABA shunt enzymes such as glutamic acid decarboxylase 67 (GAD67), GABA transaminse (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) in the hippocampal CA1 region after 5 min of transient forebrain ischemia in gerbils. For this, vehicle (physiological saline) or ebselen was administered 30 min before or after ischemia/reperfusion and sacrificed 4 days after ischemia/reperfusion. The administration of ebselen significantly reduced the neuronal death in the CA1 region induced by ischemia/reperfusion. In addition, treatment with ebselen markedly elevated GAD67, GABA-T and SSADH immunoreactivity and their protein levels compared to that in the vehicle-treated group, respectively. These results suggest that ebselen protects neurons from ischemic damage via control of the expressions of GABA shunt enzymes to enter the TCA cycle.

Comparison of neuroprotective effects of five major lipophilic diterpenoids from Danshen extract against experimentally induced transient cerebral ischemic damage

We observed neuroprotective effects of five major lipophilic diterpenes derived from Danshen (Radix Salvia miltiorrhiza) extract, such as cryptotanshinone (CTs), dihydrotanshinone I (DTsI), tanshinone I (TsI), tanshinone IIA (TsIIA) and tanshinone IIB (TsIIB), in the hippocampal CA1 region (CA1) against transient ischemic damage in gerbils. These diterpenes were administered 30min before ischemia-reperfusion and the animals were sacrificed 4days after ischemia-reperfusion. In the vehicle-treated-group, cresyl violet positive (CV(+)) cells and neuronal nuclei (NeuN)(+) neurons were significantly decreased in the CA1. However, in the TsI- and CTs-treated-ischemia-groups, CV(+) and NeuN(+) neurons were abundant in the CA1. In the other groups, the number of CV(+) and NeuN(+) neurons was less than the TsI- and CTs-treated-ischemia-groups. In addition, gliosis induced by ischemic damage was apparently blocked in the TsI- and CTs-treated-ischemia-groups. These results suggest that TsI and CTs among five major lipophilic diterpenes have strong potentials for neuroprotection against ischemic damage.

Long-term changes in neuronal degeneration and microglial activation in the hippocampal CA1 region after experimental transient cerebral ischemic damage

Delayed neuronal death following transient cerebral ischemia is mixed with apoptosis and necrosis, and the activation of microglia are activated after the ischemic insult. In the present study, we examined the long-term changes in neuronal degeneration and microglial activation in the gerbil hippocampal CA1 region after 5min of transient cerebral ischemia using specific markers for neuronal damage and microliosis. Transient ischemia-induced neuronal death was shown in CA1 pyramidal cells 4days after ischemia/reperfusion (I/R). However, neuronal degeneration of the pyramidal cells were observed up to 45days in the CA1 region after I/R. Microglial activation was also observed in the CA1 region after I/R. Isolectin B4- (IB4) immunoreactive ((+)) microglia appeared in the CA1 region 4days after I/R. On the other hand, ionized calcium-binding adapter molecule 1 (Iba-1)(+) microglia was markedly increased after I/R, and peaked at 15days after I/R. Thereafter, Iba-1 immunoreactivity was decreased with time-dependant manner in the ischemic CA1 region. These results indicate that neuronal degeneration of CA1 pyramidal cells may last about 45days in the CA1 region after ischemic damage, and microglial activation may be diverse according to their function, such as phagocytosis, after I/R.