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To explore the functional changes of the frontal eye field (FEF) and relevant brain regions and its role in the pathogenesis of intermittent exotropia (IXT) children via functional magnetic resonance imaging (fMRI). Twenty‐four IXT children (mean age, 11.83 ± 1.93 years) and 28 normal control (NC) subjects (mean age, 11.11 ± 1.50 years) were recruited. During fMRI scans, the IXT children and NCs were provided with static visual stimuli (to evoke sensory fusion) and dynamic visual stimuli (to evoke motor fusion and vergence eye movements) with binocular disparity. Brain activation in the relevant brain regions and clinical characteristics were evaluated. Group differences of brain activation and brain‐behavior correlations were investigated. For dynamic and static visual disparity relative to no visual disparity, reduced brain activation in the right FEF and right inferior occipital gyrus (IOG), and increased brain activation in the left middle temporal gyrus complex (MT+) were found in the IXT children compared with NCs. Significant positive correlations between the fusional vergence amplitude and the brain activation values were found in the right FEF, right IPL, and left cerebellum in the NC group. Positive correlations between brain activation values and Newcastle Control Scores (NCS) were found in the left MT+ in the IXT group. For dynamic visual disparity relative to static visual disparity, reduced brain activation in the right middle occipital gyrus, left cerebellum, and bilateral IPL was found in the IXT children compared with NCs. Significant positive correlations between brain activation values and the fusional vergence amplitude were found in the right FEF and right cerebellum in the NC group. Negative correlations between brain activation values and NCS were found in the right middle occipital gyrus, right cerebellum, left IPL, and right FEF in the IXT group. These results suggest that the reduced brain activation in the right FEF, left IPL, and cerebellum may play an important role in the pathogenesis of IXT by influencing fusional vergence function. While the increased brain activation in the left MT+ may compensate for this dysfunction in IXT children. [ABSTRACT FROM AUTHOR]

KCNQ/M potassium channels play a vital role in neuronal excitability; however, it is required to explore their pharmacological modulation on N‐Methyl‐ d‐aspartic acid receptors (NMDARs)‐mediated glutamatergic transmission of neurons upon ischemic insults. In the current study, both presynaptic glutamatergic release and activities of NMDARs were measured by NMDAR‐induced miniature excitatory postsynaptic currents (mEPSCs) in cultured cortical neurons of C57 mice undergoing oxygen and glucose deprivation (OGD) or OGD/reperfusion (OGD/R). The KCNQ/M‐channel opener, retigabine (RTG), suppressed the overactivation of postsynaptic NMDARs induced by OGD and then NO transient; RTG also decreased OGD‐induced neuronal death measured with MTT assay, suggesting the beneficial role of KCNQ/M‐channels for the neurons exposed to ischemic insults. However, when the neurons exposed to the subsequent reperfusion, KCNQ/M‐channels played a differential role from its protective effect. OGD/R increased presynaptic glutamatergic release, which was further augmented by RTG or decreased by KCNQ/M‐channel blocker, XE991. Reactive oxygen species (ROS) were produced partly in a NO‐dependent manner. In addition, XE991 decreased neuronal injuries upon reperfusion measured with DCF and PI staining. Meanwhile, the addition of RTG upon OGD or XE991 upon reperfusion can reverse OGD or OGD/R‐reduced mitochondrial membrane potential. Our present study indicates the dual role of KCNQ/M‐channels in OGD and OGD/R, which will decide the fate of neurons. Provided that activation of KCNQ/M‐channels has differential effects on neuronal injuries during OGD or OGD/R, we propose that therapy targeting KCNQ/M‐channels may be effective for ischemic injuries but the proper timing is so crucial for the corresponding treatment. [ABSTRACT FROM AUTHOR]

Remote ischemic postconditioning (RIPC) is a promising neuroprotective strategy for ischemic stroke. Here, we employed a focal ischemic stroke mouse model to test the hypothesis that poststroke collateral circulation as a potent mechanism of action underlying the therapeutic effects of immediate RIPC. During reperfusion of cerebral ischemia, the mice were randomly assigned to receive RIPC, granulocyte colony‐stimulating factor (G‐CSF) as a positive control, or no treatment. At 24 hr, we found RIPC and G‐CSF increased monocytes/macrophages in the dorsal brain surface and in the spleen, coupled with enhanced leptomeningeal collateral flow compared with nontreatment group. Blood monocytes depletion by 5‐fluorouracil (5‐FU) significantly limited the neuroprotection of RIPC or G‐CSF treatment. The protein expression of proangiogenic factors such as Ang‐2 was increased by ischemia, but treatment with either RIPC or G‐CSF showed no further upregulation. Thus, immediate RIPC confers neuroprotection, in part, by enhancing leptomeningeal collateral circulation in a mouse model of ischemic stroke. [ABSTRACT FROM AUTHOR]

Stroke is one of the leading causes of death in the world, but its underlying mechanisms remain unclear. Both conventional protein kinase C ( cPKC)γ and ubiquitin C-terminal hydrolase L1 ( UCHL1) are neuron-specific proteins. In the models of 1-hr middle cerebral artery occlusion ( MCAO)/24-hr reperfusion in mice and 1-hr oxygen-glucose deprivation ( OGD)/24-hr reoxygenation in cortical neurons, we found that cPKCγ gene knockout remarkably aggravated ischaemic injuries and simultaneously increased the levels of cleaved (Cl)-caspase-3 and LC3-I proteolysis product LC3- II, and the ratio of TUNEL-positive cells to total neurons. Moreover, cPKCγ gene knockout could increase UCHL1 protein expression via elevating its mRNA level regulated by the nuclear factor κB inhibitor alpha (IκB-α)/nuclear factor κB ( NF-κB) pathway in cortical neurons. Both inhibitor and sh RNA of UCHL1 significantly reduced the ratio of LC3- II/total LC3, which contributed to neuronal survival after ischaemic stroke, but did not alter the level of Cl-caspase-3. In addition, UCHL1 sh RNA reversed the effect of cPKCγ on the phosphorylation levels of mTOR and ERK rather than that of AMPK and GSK-3β. In conclusion, our results suggest that cPKCγ activation alleviates ischaemic injuries of mice and cortical neurons through inhibiting UCHL1 expression, which may negatively regulate autophagy through ERK- mTOR pathway. [ABSTRACT FROM AUTHOR]

We previously reported that conventional protein kinase C (c PKC)β participated in hypoxic preconditioning-induced neuroprotection against cerebral ischemic injury, and collapsin response-mediated protein 2 ( CRMP2) was identified as a c PKCβ interacting protein. In this study, we explored the regulation of CRMP2 phosphorylation and proteolysis by c PKCβ, and their role in ischemic injury of oxygen-glucose deprivation ( OGD)-treated cortical neurons and brains of mice with middle cerebral artery occlusion-induced ischemic stroke. The results demonstrated that c PKCβ-mediated CRMP2 phosphorylation via the c PKCβ-selective activator 12-deoxyphorbol 13-phenylacetate 20-acetate ( DOPPA) and inhibition of calpain-mediated CRMP2 proteolysis by calpeptin and a fusing peptide containing TAT peptide and the calpain cleavage site of CRMP2 ( TAT- CRMP2) protected neurons against OGD-induced cell death through inhibiting CRMP2 proteolysis in cultured cortical neurons. The OGD-induced nuclear translocation of the CRMP2 breakdown product was inhibited by DOPPA, calpeptin, and TAT- CRMP2 in cortical neurons. In addition, both c PKCβ activation and CRMP2 proteolysis inhibition by hypoxic preconditioning and intracerebroventricular injections of DOPPA, calpeptin, and TAT- CRMP2 improved the neurological deficit in addition to reducing the infarct volume and proportions of cells with pyknotic nuclei in the peri-infact region of mice with ischemic stroke. These results suggested that c PKCβ modulates CRMP2 phosphorylation and proteolysis, and c PKCβ activation alleviates ischemic injury in the cultured cortical neurons and brains of mice with ischemic stroke through inhibiting CRMP2 proteolysis by phosphorylation. [ABSTRACT FROM AUTHOR]

Purpose To assess whether a Valsalva manoeuver influences intra-ocular pressure ( IOP), cerebrospinal fluid pressure ( CSF- P) and, by a change in the trans-laminar cribrosa pressure difference, optic nerve head morphology. Methods In the first part of the study, 20 neurological patients (study group 'A') underwent measurement of IOP and lumbar CSF-P measurement in a lying position before and during a Valsalva manoeuver. In the second study part, 20 healthy subjects (study group 'B') underwent ocular tonometry and confocal scanning laser tomography of the optic nerve head before and during a Valsalva manoeuver. Results During the Valsalva manoeuver in study group 'A', the increase in CSF-P by 10.5 ± 2.7 mmHg was significantly (p < 0.001) higher than the increase in IOP by 1.9 ± 2.4 mmHg. The change in CSF-P was not significantly (p = 0.61) correlated with the change in IOP. During the Valsalva manoeuver in study group 'B', IOP increased by 4.5 ± 4.2 mmHg and optic cup volume (p < 0.001), cup/disc area ratio (p = 0.02), cup/disc diameter ratio (p = 0.03) and maximum optic cup depth (p = 0.01) significantly decreased, while neuroretinal rim volume (p = 0.005) and mean retinal nerve fibre layer thickness (p = 0.02) significantly increased. Conclusions The Valsalva manoeuver-associated short-term increase in CSF-P was significantly larger than a simultaneous short-term increase in IOP. It led to a Valsalva manoeuver-associated decrease or reversal of the trans-laminar cribrosa pressure difference, which was associated with a change in the three-dimensional optic nerve head morphology: optic cup-related parameters decreased and neuroretinal rim-related parameters enlarged. These findings may be of interest for the pathogenesis of glaucomatous optic neuropathy. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2012) 120, 830-841. Abstract We previously reported the involvement of conventional protein kinase C (cPKC) βII, γ, novel PKC (nPKC) ε and their interacting proteins in hypoxic pre-conditioning (HPC)-induced neuroprotection. In this study, the large-scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs and their PKC-isoform specific gene network in mouse brain after HPC and 6 h middle cerebral artery occlusion (MCAO). We found 4 up-regulated and 13 down-regulated miRNAs in the cortex of HPC mice, 26 increased and 39 decreased gene expressions of miRNAs in the peri-infarct region of 6 h MCAO mice, and 11 up-regulated and 22 down-regulated miRNAs in the peri-infarct region of HPC and 6 h MCAO mice. Based on Diff Score, 19 differentially expressed miRNAs were identified in HPC and 6 h MCAO mouse brain. Then the miRNA-gene-network of 19 specified miRNAs target genes of cPKCβII, γ and nPKCε-interacting protein was predicted by using bioinformatics analysis of genome databases. Furthermore, the down-regulated miR-615-3p during HPC had a detrimental effect on the oxygen-glucose deprivation (OGD)-induced N2A cell injury. These results suggested that the identified 19 miRNAs, notably miR-615-3p, might target these genes of cPKCβII, γ and nPKCε-interacting proteins involved in HPC-induced neuroprotection. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Valsalva manoeuver, intraocular pressure, cerebrospinal fluid pressure, optic disc topography: Beijing intracranial and intra-ocular pressure study" in 2013 issue is presented.