Extracellular regulated kinase (ERK) transduce growth factor signals while c-Jun NH(2)-terminal kinase (JNK) delivers stress signals into the nuclei for regulation of gene expression. These signaling pathways were studied by laser-scanning confocal microcopy and Western blot analysis using phospho-specific antibodies on rat brains that were subjected to 15 minutes transient forebrain ischemia followed by varied periods of reperfusion. Extracellular regulated kinase was activated at 30 minutes and 4 hours of reperfusion in the nuclei and dendrites of surviving dentate gyrus (DG) cells, but not in dying CA1 neurons after ischemia. Tyrosine phosphorylation of Trk kinase, an ERK upstream growth factor receptor, was elevated in the DG tissue, and to a lesser extent in the CA1 region. In addition, phosphorylation of activating transcription factor-2 (ATF-2) and c-Jun was selectively increased in CA1 dying neurons during the late period of reperfusion. These findings suggested that the Trk-ERK signaling pathway might be neuroprotective for dentate granule cells. The activation of ATF-2 and c-Jun pathways in the late period of reperfusion in CA1 dying neurons might reflect damage signals in these neurons. These results suggested that the lack of protective signals acting in concert with the presence of damage signals in CA1 neurons after ischemia might contribute to delayed neuronal death after transient forebrain ischemia.

Purpose To characterise longitudinal changes in the retinal microvasculature of type 2 diabetes mellitus (T2DM) as exemplified in a patient with proliferative diabetic retinopathy (PDR) using an adaptive optics scanning light ophthalmoscope (AOSLO). Methods A 35 year old T2DM patient with PDR treated with scatter pan-retinal photocoagulation at the inferior retina one day prior to initial AOSLO imaging along with a 24 year old healthy control were imaged in this study. AOSLO vascular structural and perfusion maps were acquired at four visits over a 20 week period. Capillary diameter and microaneurysm area changes were measured on the AOSLO structural maps. Imaging repeatability was established using longitudinal imaging of microvasculature in the healthy control. Results Capillary occlusion and recanalisation, capillary dilatation, resolution of local retinal haemorrhage, capillary hairpin formation, capillary bend formation, microaneurysm formation, progression and regression were documented over time in a region 2° superior to the fovea in the PDR patient. An identical microvascular network with same capillary diameter was observed in the control subject over time. Conclusions High-resolution serial AOSLO imaging enables in vivo observation of vasculopathic changes seen in diabetes mellitus. The implications of this methodology are significant, providing the opportunity for studying the dynamics of the pathological process, as well as the possibility of identifying highly sensitive and non-invasive biomarkers of end organ damage and response to treatment.

Polymethyl methacrylate (PMMA)-augmented cannulated pedicle-screw fixation has been routinely performed for the surgical treatment of lumbar degenerative diseases. Despite its satisfactory clinical outcomes and prevalence, problems and complications associated with high-strength, stiff, and nondegradable PMMA have largely hindered the long-term efficacy and safety of pedicle-screw fixation in osteoporotic patients. To meet the unmet need for better bone cement for cannulated pedicle-screw fixation, a new injectable and biodegradable nanocomposite that was the first of its kind was designed and developed in the present study. The calcium phosphate-based nanocomposite (CPN) exhibited better anti-pullout ability and similar fluidity and dispersing ability compared to clinically used PMMA, and outperformed conventional calcium phosphate cement (CPC) in all types of mechanical properties, injectability, and biodegradability. In term of axial pullout strength, the CPN-augmented cannulated screw reached the highest force of ~120 N, which was higher than that of PMMA (~100 N) and CPC (~95 N). The compressive strength of the CPN (50 MPa) was three times that of CPC, and the injectability of the CPN reached 95%. In vivo tests on rat femur revealed explicit biodegradation of the CPN and subsequent bone ingrowth after 8 weeks. The promising results for the CPN clearly suggest its potential for replacing PMMA in the application of cannulated pedicle-screw fixation and its worth of further study and development for clinical uses.

Purpose Eyes fellow to nonischemic central retinal vein occlusion (CRVO) were examined for abnormalities, which might explain their increased risk for future occlusion, using adaptive optics scanning light ophthalmoscope fluorescein angiography. Methods Adaptive optics scanning light ophthalmoscope fluorescein angiography foveal microvascular densities were calculated. Nonperfused capillaries adjacent to the foveal avascular zone were identified. Spectral domain optical coherence tomography, ultrawide field fluorescein angiographies, and microperimetry were also performed. Results Ten fellow eyes of nine nonischemic CRVO and 1 nonischemic hemi-CRVO subjects and four affected eyes of three nonischemic CRVO and one nonischemic hemi-CRVO subjects were imaged. Ninety percent of fellow eyes and 100% of affected eyes demonstrated at least 1 nonperfused capillary compared with 31% of healthy eyes. Fellow eye microvascular density (35 ± 3.6 mm−1) was significantly higher than that of affected eyes (25 ± 5.2 mm−1) and significantly lower than that of healthy eyes (42 ± 4.2 mm−1). Compared with healthy controls, spectral domain optical coherence tomography thicknesses showed no significant difference, whereas microperimetry and 2/9 ultrawide field fluorescein angiography revealed abnormalities in fellow eyes. Conclusion Fellow eye changes detectable on adaptive optics scanning light ophthalmoscope fluorescein angiography reflect subclinical pathology difficult to detect using conventional imaging technologies. These changes may help elucidate the pathogenesis of nonischemic CRVO and help identify eyes at increased risk of future occlusion.