Eco-friendly luminescent solar concentrators with low reabsorption losses and resistance to concentration quenching based on aqueous-solution-processed thiolate-gold nanoclusters.

Heavy-metal-containing quantum dots (QDs) with engineered electronic states have been served as luminophores in luminescent solar concentrators (LSCs) with impressive optical efficiency. Unfortunately, those QDs involve toxic elements and need to be synthesized in a hazardous solvent. Recently, biocompatible, eco-friendly gold nanoclusters (AuNCs), which can be directly synthesized in an aqueous solution, have gained much attention for promising applications in 'green photonics'. Here, we explored the solid-state photophysical properties of aqueous-solution-processed, glutathione-stabilized gold nanoclusters (GSH-AuNCs) with a ligand-to-metal charge-transfer (LMCT) state for developing 'green' LSCs. We found that such GSH-AuNCs exhibit a large Stokes shift with almost no spectral overlap between the optical absorption and PL emission due to the LMCT states, thus, suppressing reabsorption losses. Compared with GSH-AuNCs in solution, the photoluminescence quantum yields (PL-QYs) of the LSCs can be enhanced, accompanied with a lengthened PL lifetime owing to the suppression of non-radiative recombination rates. In addition, the LSCs do not suffer from severe concentration-induced PL quenching, which is a common weakness for conventional luminophores. As a result, a common trade-off between light-harvesting efficiency and solid-state PL-QYs can be bypassed due to nearly-zero spectral overlap integral between the optical absorption and PL emission. We expect that GSH-AuNCs hold great promise for serving as luminophores for 'green' LSCs by further enhancing solid-state PL-QYs.

Synthesis of N-doped graphene quantum dots by pulsed laser ablation with diethylenetriamine (DETA) and their photoluminescence.

We report a facile, fast, and one-step approach to prepare N-doped graphene quantum dots (GQDs) using pulsed laser ablation with diethylenetriamine (DETA). The synthesized N-doped GQDs with an average size of about 3.4 nm and an N/C atomic ratio of 26% have been demonstrated. Compared to pristine GQDs, the N-doped GQDs emit enhanced photoluminescence (PL) with a factor as high as 66, originated from the enhanced densities of pyridinic and graphitic N. The temperature-dependent PL of the N-doped GQDs was studied from cryogenic to room temperature. An anomalous temperature dependence of PL intensity was observed for the N-doped GQDs, which was ascribed to a carrier transfer mechanism from a dopant-induced state to the quantum-dot emitting state.

Solid-state, ambient-operation thermally activated delayed fluorescence from flexible, non-toxic gold-nanocluster thin films: towards the development of biocompatible light-emitting devices.

Luminescent gold nanoclusters (AuNCs) with good biocompatibility have gained much attention in bio-photonics. In addition, they also exhibit a unique photo-physical property, namely thermally activated delayed fluorescence (TADF), by which both singlet and triplet excitons can be harvested. The combination of their non-toxic material property and unique TADF behavior makes AuNCs biocompatible nano-emitters for bio-related light-emitting devices. Unfortunately, the TADF emission is quenched when colloidal AuNCs are transferred to solid states under ambient environment. Here, a facile, low-cost and effective method was used to generate efficient and stable TADF emissions from solid AuNCs under ambient environment using polyvinyl alcohol as a solid matrix. To unravel the underlying mechanism, temperature-dependent static and transient photoluminescence measurements were performed and we found that two factors are crucial for solid TADF emission: small energy splitting between singlet and triplet states and the stabilization of the triplet states. Solid TADF films were also deposited on the flexible plastic substrate with patterned structures, thus mitigating the waveguide-mode losses. In addition, we also demonstrated that warm white light can be generated based on a co-doped single emissive layer, consisting of non-toxic, solution-processed TADF AuNCs and fluorescent carbon dots under UV excitation.

Origin of tunable photoluminescence from graphene quantum dots synthesized via pulsed laser ablation.

A one-step synthesis of graphene quantum dots (GQDs) has been implemented using pulsed laser ablation (PLA) with carboxyl-functionalized multiwalled carbon nanotubes (MWCNTs). The synthesized GQDs with an average size smaller than 3 nm were obtained by the fragmentation of MWCNTs via oxidative cutting. The GQDs can generate tunable photoluminescence (PL) ranging from green to blue by controlling the PLA time. The PL spectrum (decay time) of the green GQDs remains unchanged under different excitation energies (emission energies), while that of the blue GQDs correlates with the excitation energy (emission energy). On the basis of the pH and temperature dependence of PL, we suggest that the localized intrinsic states associated with the sp(2) nanodomains and delocalized extrinsic states embedded on the GQD surface are responsible for blue and green emission in GQDs, respectively.

Distance dependence of energy transfer from InGaN quantum wells to graphene oxide.

We report the distance-dependent energy transfer from an InGaN quantum well to graphene oxide (GO) by time-resolved photoluminescence (PL). A pronounced shortening of the PL decay time in the InGaN quantum well was observed when interacting with GO. The nature of the energy-transfer process has been analyzed, and we find the energy-transfer efficiency depends on the 1/d² separation distance, which is dominated by the layer-to-layer dipole coupling.

Efficient energy transfer from InGaN quantum wells to Ag nanoparticles.

Nonradiative energy transfer from an InGaN quantum well to Ag nanoparticles is unambiguously demonstrated by the time-resolved photoluminescence. The distance dependence of the energy transfer rate is found to be proportional to 1/d(3), in good agreement with the prediction of the dipole interaction calculated from the Joule losses in acceptors. The maximum energy-transfer efficiency of this energy transfer system can be as high as 83%.

Probing the photoluminescence properties of gold nanoclusters by fluorescence lifetime correlation spectroscopy.

Gold nanoclusters (Au NCs) have attracted much attention for promising applications in biological imaging owing to their tiny sizes and biocompatibility. So far, most efforts have been focused on the strategies for fabricating high-quality Au NCs and then characterized by conventional ensemble measurement. Here, a fusion single-molecule technique combining fluorescence correlation spectroscopy and time-correlated single-photon counting can be successfully applied to probe the photoluminescence (PL) properties for sparse Au NCs. In this case, the triplet-state dynamics and diffusion process can be observed simultaneously and the relevant time constants can be derived. This work provides a complementary insight into the PL mechanism at the molecular levels for Au NCs in solution.

Energy transfer from InGaN quantum wells to Au nanoclusters via optical waveguiding.

We present the first observation of resonance energy transfer from InGaN quantum wells to Au nanoclusters via optical waveguiding. Steady-state and time-resolved photoluminescence measurements provide conclusive evidence of resonance energy transfer and obtain an optimum transfer efficiency of ~72%. A set of rate equations is successfully used to model the kinetics of resonance energy transfer.

Clinical manifestation of esophageal carcinosarcoma: a Taiwan experience.

Carcinosarcoma of the esophagus is a rare neoplasm with both carcinomatous and sarcomatous components. This study aimed to investigate its clinicopathologic features and endoscopic characteristics. The data of patients diagnosed to have esophageal carcinosarcoma pathologically in the past 30 years (January 1976-December 2007) were reviewed. Of 3318 cases of esophageal malignancy, 12 were diagnosed as esophageal carcinosarcoma, with an incidence of 0.36%. All of the cases were male with a mean age of 62.3 years. Of the 12 tumors, 8 were polypoid type, and 4 were ulcerative type. In the endoscopic ultrasonography examination, the tumors show heterogeneous hypoechoic lesions with irregular outer margins and internal multicystic components. Four patients (33.3%) had previous head and neck squamous cell carcinoma that occurred metachronously. This is the first report about the characteristics of esophageal carcinosarcoma under endoscopic ultrasonography examination. The relationship between esophageal carcinosarcomas and head and neck cancer needs further investigation.

Photo-induced Doping in GaN Epilayers with Graphene Quantum Dots.

We demonstrate a new doping scheme where photo-induced carriers from graphene quantum dots (GQDs) can be injected into GaN and greatly enhance photoluminescence (PL) in GaN epilayers. An 8.3-fold enhancement of PL in GaN is observed after the doping. On the basis of time-resolved PL studies, the PL enhancement is attributed to the carrier transfer from GQDs to GaN. Such a carrier transfer process is caused by the work function difference between GQDs and GaN, which is verified by Kelvin probe measurements. We have also observed that photocurrent in GaN can be enhanced by 23-fold due to photo-induced doping with GQDs. The improved optical and transport properties from photo-induced doping are promising for applications in GaN-based optoelectronic devices.

A Facile and Low-Cost Method to Enhance the Internal Quantum Yield and External Light-Extraction Efficiency for Flexible Light-Emitting Carbon-Dot Films.

Solution-processed, non-toxic carbon dots (CDs) have attracted much attention due to their unique photoluminescence (PL) properties. They are promising emissive layers for flexible light-emitting devices. To this end, the CDs in pristine aqueous solutions need to be transferred to form solid-state thin films without sacrificing their original PL characteristics. Unfortunately, solid-state PL quenching induced by extra non-radiative (NR) energy transfer among CDs would significantly hinder their practical applications in optoelectronics. Here, a facile, low-cost and effective method has been utilized to fabricate high-performance CD/polymer light-emitting flexible films with submicron-structured patterns. The patterned polymers can serve as a solid matrix to disperse and passivate CDs, thus achieving high internal quantum yields of 61%. In addition, they can act as an out-coupler to mitigate the waveguide-mode losses, approximately doubling the external light-extraction efficiency. Such CD/polymer composites also exhibit good photo-stability, and thus can be used as eco-friendly, low-cost phosphors for solid-state lighting.

Laser-ablation production of graphene oxide nanostructures: from ribbons to quantum dots.

A new one-step method for the preparation of graphene oxide (GO) nanostructures has been developed by pulsed laser ablation in GO solution. The formation of different shapes of GO nanostructures, such as ribbons, nanoflakes (including nano-squares, nano-rectangles, nano-triangles, nano-hexagons, and nano-disks) and quantum dots, has been demonstrated by scanning electron microscopy and transmission electron microscopy. Photoreduction for the GO occurred during irradiation by the pulsed laser. The GO quantum dots exhibit a blue photoluminescence, originating from recombination of the localized carriers in the zigzag-edge states.

Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion.

The angiopoietin/Tie receptor system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Angpo-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a focal cerebral ischemia model in rats. The cDNA fragments obtained from reverse transcription polymerase chain reaction amplification were cloned and used as a probe to detect individual genes. Northern blot analysis showed a delayed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ischemia, eightfold higher than the values of the sham-operated controls. A biphasic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hours (6.4-fold) and 2 weeks (4.6-fold) after ischemia. The expression of Tie-2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 kb) also increased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these genes were different from those of other angiogenic genes such as basic fibrobast growth factor/fibroblast growth factor receptor and vascular endothelial growth factor/vascular endothelial growth factor receptor and proteolytic enzymes (tissue-type plasminogen activator and urokinase plasminogen activator) and their inhibitors (plasminogen activator inhibitor-1). The expression patterns of these genes could be related to progressive tissue liquefaction and neovascularization after ischemia in this stroke model. Differential expression of these angiogenesis genes suggests the involvement of complex regulatory mechanisms that remain to be characterized.

Induction of Tie-1 and Tie-2 receptor protein expression after cerebral ischemia-reperfusion.

Tie-1 and Tie-2 are receptor tyrosine kinases (RTKs) that are exclusively expressed in endothelial cells and play important roles in endothelial cell biology. The authors have reported previously the temporal profiles of Tie-1 and Tie-2 mRNA expression after focal cerebral ischemia-reperfusion. In the current study, the localization of Tie-1/Tie-2 mRNA and proteins were further investigated in the same focal ischemia model. In situ hybridization showed that, after 60-minute ischemia and 72-hour reperfusion, both Tie-1 and Tie-2 mRNA appeared as capillary-like structures in the ischemic middle cerebral artery (MCA) cortex. Western blot analysis showed a biphasic expression of Tie-1 protein in the same region. The first peak, spanning the ischemic and early reperfusion period. was of low intensity and short-lived. The second peak was of greater intensity and spanning the period from 72 to 168 hours after reperfusion. Similarly, Tie-2 expression at the protein level also exhibited a biphasic pattern. Immunohistochemical studies, after 72 hours of reperfusion, showed that although Tie-1 and Tie-2 were detected within the ischemic cortex, they actually were expressed in different populations of endothelial cells in different regions. In agreement with the in situ hybridization study, Tie-1 immunoreactivity appeared as capillary-like structures in cortical layers 2 to 4. Similar capillary-like appearance of Tie-2 immunoreactivity was noted in the outer cortical layers. In addition, Tie-2 immunoreactivity also was observed in cortical layer 6b, where de novo large vessel formation was noted. Cellular colocalization experiments revealed that Tie-2 is expressed in proximity to its antagonist, Angpo-2, as well as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in cortical layer 1, where active vessel remodeling was noted. Interestingly, bFGF only partially colocalized with VEGF, suggesting differential roles for these angiogenic factors during vessel remodeling. Tie-1 protein, to a lesser degree, also colocalized with Angpo-2, bFGF, and VEGF in cortical layer 1. Magnetic resonance imaging (MRI) showed increased regional cerebral blood flow (CBF) corresponding to the expression of these angiogenesis gene products. Together, these findings suggest that the evolving expression of angiogenesis genes underlie the robust vascular remodeling after ischemia and reperfusion.

Differential regulation of H- and L-ferritin messenger RNA subunits, ferritin protein and iron following focal cerebral ischemia-reperfusion.

Iron may catalyse the production of reactive oxygen species during post-ischemic reoxygenation and subsequently lead to brain damage. Ferritin, an iron sequestering and storage protein, can also be a source of iron after ischemic insult. However, its role in ischemia-reperfusion has not been carefully investigated. In the present study, we examined the temporal and spatial induction profiles of both H- and L-ferritin messenger RNA and protein in a well-defined focal cerebral ischemia model. Results of northern blot analysis showed a delayed and prolonged induction of both H- and L-ferritin messenger RNA in the ischemic cortex of rats subjected to 60min ischemic insult. A significant induction of both H- and L-ferritin messenger RNA was observed at 12h and remained elevated for up to 336h after the onset of reperfusion. At the peak level, quantitative analysis of the blot indicated a 2.5-fold and a six-fold increase in H- and L-ferritin messenger RNA, respectively, compared with the sham-operated controls. No apparent change in the levels of either messenger RNA was observed in the contralateral side. Results of in situ hybridization studies revealed constitutive expression of both H- and L-ferritin messenger RNA throughout the brain in sham-operated animals, in particular the hippocampus and the piriform cortex. Nevertheless, the signal intensity of H-ferritin messenger RNA was much higher than that of L-ferritin messenger RNA. Seventy-two hours after 60min ischemia, marked expression of H-ferritin messenger RNA was observed in the area surrounding the middle cerebral artery irrigated cortex, the medial part of the caudoputamen and in the subfield of the CA1 hippocampal region of the ipsilateral hemisphere. Similarly, a large induction of L-ferritin messenger RNA was also noted in several areas, including the middle cerebral artery irrigated cortex, the lateral part of the caudoputamen and the stratum pyramidale of the CA1 hippocampal region, which were totally different from areas where H-ferritin messenger RNA was found. At 336h after ischemia, increased expression of H-ferritin messenger RNA was observed in the peri-necrosis and ipsilateral thalamus regions, while L-ferritin messenger RNA was noted exclusively at the edge within the necrosis. Results of immunohistochemical study further revealed that ferritin immunoreactivity was present in the same areas where increased ferritin messenger RNA was found. Sixty-minute ischemia also led to iron deposition in discrete areas. Iron deposition was highly associated with the induction of ferritin, particularly in the macrophage- and microglia-positive areas where cell death or tissue necrosis was noted.In summary, our initial findings indicate that ischemic insult leads to induction of both H- and L-ferritin messenger RNA. In the present study, although the temporal induction profiles were similar, the major expression areas for these two genes were totally different. Ferritin immunoreactivity was observed in the same areas where increased ferritin messenger RNA was found. Ischemia also resulted in iron deposition, which highly associated with the ferritin immunoreactivity. The exact regulatory mechanism and pathological significance for the differential expression of H- and L-ferritin genes following ischemia/reperfusion remain to be clarified.

Elevated basic fibroblast growth factor levels in stroke-prone spontaneously hypertensive rats.

Basic fibroblast growth factor is a biologically active polypeptide with mitogenic, angiogenic and neurotrophic properties. In the present study, the temporal and spatial expressions of basic fibroblast growth factor in stroke-prone spontaneously hypertensive rats were compared to two related strains of rat: spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Higher levels of total RNA concentration were found in cerebral cortex of four-week-old stroke-prone rats compared to spontaneously hypertensive rats and Wistar Kyoto rats. Northern blot analysis showed no changes in levels of basic fibroblast growth factor messenger RNA with increasing age in cerebral cortex of Wistar Kyoto and spontaneously hypertensive rats. However, significant increases were found in 26- and 38-week-old stroke-prone rats compared to four-week-old stroke-prone rats. Although messenger RNA increases were also found in subcortical and cerebellar regions, a significant difference in levels of basic fibroblast growth factor messenger RNA was observed only in cerebral cortices among these three strains. This age-related increase in basic fibroblast growth factor messenger RNA correlated with the increase incidence of stroke in stroke-prone rats. Immunohistochemical study further revealed a dramatic increase in levels of basic fibroblast growth factor immunoreactivity in cerebral cortex of 30-week-old stroke-prone rats as compared to young stroke-prone rats, as well as age-matched Wistar Kyoto and spontaneously hypertensive rats. This increase in basic fibroblast growth factor immunoreactivity therefore appears very specific to aged stroke-prone rats. However, immunoreactivity decreased once severe tissue damages were observed in the cerebral cortex. Basic fibroblast growth factor-positive cells were diffusely expressed in cerebral cortex; double staining with glial fibrillary acidic protein showed the majority of these basic fibroblast growth factor-positive cells to be astrocytes. In summary, although young stroke-prone spontaneously hypertensive rats showed significantly higher RNA concentration, significant increases in levels of basic fibroblast growth factor, including both messenger RNA and protein expression, were observed in aged stroke-prone rats with a high incidence of stroke. These findings suggest the possibility that basic fibroblast growth factor may play a role in the developmental sequelae of cerebral lesions in stroke-prone spontaneously hypertensive rats.

Inhibition of the mitochondrial Mg2+-ATPase by propranolol.

The in vitro effects of propranolol, a commonly used beta-adrenergic blocker, on the membrane structure and function of rat heart mitochondria were investigated. It was found that the respiratory control and oxidative phosphorylation of the isolated mitochondria decreased concomitantly when the drug was added to the assay medium. At the concentration higher than 1.0 X 10(-4) M, propranolol significantly inhibited the State 3 respiration but had little effect on the State 4 respiration of the mitochondria. On the other hand, the drug exhibited noncompetitive inhibitions toward the Mg2+-ATPase activity of submitochondrial particles and purified enzyme preparations at the concentrations ranging from 3.0 X 10(-4) to 1.5 X 10(-3) M. The inhibitory constants of propranolol toward the enzyme activity in submitochondrial particles and in the purified preparation were estimated to be 6.7 X 10(-4) and 1.4 X 10(-3) M, respectively. However, the drug did not show significant effect on the activity of any of the enzyme complexes of the mitochondrial respiratory chain. It is thus concluded that propranolol impairs the mitochondrial respiration and oxidative phosphorylation mainly through its inhibition of the Mg2+-ATPase activity of the mitochondria. This effect of propranolol may explain, at least partly, its depression effects on the cardiac functions of the animal.

Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFR alpha) expression following focal cerebral ischemia.

Ciliary neurotrophic factor (CNTF) is a member of cytokines, with trophic effects on ciliary, motor sympathetic, sensory, retinal and hippocampal neurons. In the present study, we examined the temporal and spatial expression profiles of CNTF and CNTF receptor alpha (CNTFR alpha) mRNAs in a focal cerebral ischemia model induced by transient occlusion of the right middle cerebral artery and both common carotid arteries. Northern blot analysis showed a slow and sustained increase in the 1.2 kb transcript of CNTF mRNA in the ischemic cortex of rats subjected to a transient 60 min ischemic insult. A delayed decrease in the 2.1 kb transcript of CNTFR alpha mRNA in the ischemic cortex was observed in rats subjected to 60 min ischemia followed by 72 h of reperfusion. In situ hybridization studies revealed constitutive expression of CNTFR alpha mRNA in the majority of neurons in the brain. Following 4 h of reperfusion, increased expression of CNTFR alpha mRNA was observed in the ipsilateral dentate gyrus, which is opposite to the down-regulation noted in the ischemic cortex. Within the infarct area CNTFR alpha mRNA had a marked increase in cortical layer II but a decrease in cortical layer V following 1 day of reperfusion. No signal of CNTFR alpha mRNA was detected within the infarct region following 3 days of reperfusion. Following 1 week of reperfusion, although no marked changes was observed in the level of CNTFR alpha mRNA in the area immediately surrounding the necrosis region where the reactive astrocytes were noted, a striking increase in the CNTF mRNA signal was noted. In summary, differential regulation of CNTF and CNTFR alpha mRNAs was noted in the ischemic cortex. Regional differences in CNTF receptor expression were noted between the ischemic cortex and ipsilateral dentate gyrus as well as between cortical layer II and V within the infarct region. CNTF mRNA, but not CNTFR alpha mRNA, had a marked increase in the area immediately adjacent to the necrosis. The mechanisms and patho-physiological significance for these differential regulation remain to be studied.

Induction of basic fibroblast growth factor (bFGF) expression following focal cerebral ischemia.

Basic fibroblast growth factor (bFGF) is a biologically active polypeptide with mitogenic, angiogenic, and neurotrophic properties. In the present study, we examined the temporal and spatial expression profiles of bFGF mRNA and protein concentration in a focal cerebral ischemia model induced by transient occlusion of the right middle cerebral artery (MCA) and both common carotid arteries (CCAs). Results of Northern blot analysis shows a transient 2.5-fold increase in the 6.0 kb transcript of bFGF mRNA within the ischemic cortex of rats subjected to 60 min ischemic insult followed by 12 h of reperfusion. Although enhanced expression of bFGF mRNA was also noted in the ipsilateral hippocampus, the temporal induction profile appeared to be different from that of the ischemic cortex. A significant increase in bFGF mRNA was observed as early as 60 min following ischemia and remained elevated for up to 2 weeks after the onset of reperfusion. In situ hybridization studies revealed constitutive expression of bFGF mRNA in discrete brain regions of sham-operated animals. Following 60 min ischemia and 12 h reperfusion, increased expression of bFGF mRNA was observed in the ischemic cortex (both peri-infarct and infarct area). Increased expression of bFGF mRNA within the infarcted area is largely confined rostrally to the outer cortical layers of the infarct, an area with increased density of blood vessels. bFGF-like immunoreactivity was also detected in areas expressing bFGF mRNA. Furthermore, a striking increase in bFGF-like immunoreactivity was observed in the ipsilateral hippocampus. Double-staining with anti-GFAP antibody indicated that the majority of the bFGF-like immunoreactivity was localized in the astrocytes, however, not all astrocytes showed bFGF-like immunoreactivity. Some GFAP negative cell also showed bFGF-like immunoreactivity. In summary, increased expression of both bFGF mRNA and immunoreactivity following ischemia were located in the same brain regions. An increase in bFGF-like immunoreactivity after ischemic insult is likely due to an increase in the expression of its 6.0 kb bFGF mRNA transcripts. Although increased bFGF mRNA was observed in both ischemic cortex and ipsilateral hippocampus after ischemic insult, the temporal expression profiles differed. Results from the present study raise the possibility that increased expression of bFGF in the peri-infarcted area may limit the spread of ischemic injury.

Expression of NGFI-B mRNA in a rat focal cerebral ischemia-reperfusion model.

Cerebral ischemia is known to induce the expression of several immediate early genes (IEGs), including c-fos and c-jun, which subsequently regulate a number of late effector genes. In this study, we examined the expression of NGFI-B (or nur 77) mRNA in a rat focal cerebral ischemia-reperfusion model. NGFI-B is a member of the IEGs which encodes for a nuclear receptor and is rapidly induced by nerve growth factor (NGF). Northern blot analysis showed a rapid but transient enhancement of NGFI-B mRNA, a peak level for which was observed at 30 min of reperfusion following 60 min ischemic insult. At the peak level, quantitative analysis of the blot indicated a 12-fold and 4-fold increase of NGFI-B mRNA in the ischemic cortex and ipsilateral hippocampus, respectively, as compared to the sham-operated control. No apparent changes in mRNA levels were observed within contralateral sites of the cortex. Results from in situ hybridization showed that severe ischemia (60 min) resulted in a marked increase of NGFI-B mRNA throughout the entire ischemic cerebral cortex. The increase was particularly notable in the frontal, occipital, perirhinal and piriform cortical regions and in the dentate gyrus and CAI-3 regions of the ipsilateral hippocampus. A marked induction was also noted in the ipsilateral caudate putamen. Unlike the induction profile of NGFI-B mRNA, severe ischemia resulted in bilateral increases of its family gene, NGFI-A mRNA. The spatial induction profile is similar to that of NGFI-B mRNA in both hemispheres, except within the region of the contralateral dentate gyrus which showed low levels of NGFI-A mRNA. The expression pattern of NGF and BDNF mRNA, upstream genes of NGFI-B, were also examined. Interestingly the temporal and spatial expression patterns of BDNF mRNA were very similar to that of NGFI-A mRNA under the same conditions, whereas increased NGF and NGFI-B mRNA were observed only in the ipsilateral hemisphere. It is likely that multiple and/or overlapping pathways are activated subsequent to ischemic challenge which in turn are crucial for cel survival and/or functional recovery following focal cerebral ischemia.