The longitudinal changes of BOLD response and cerebral hemodynamics from acute to subacute stroke. A fMRI and TCD study

<p>Abstract</p> <p>Background</p> <p>By mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke.</p> <p>This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response.</p> <p>We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases.</p> <p>Results</p> <p>As patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearman's rho = 0.734; p = 0.01).</p> <p>Conclusions</p> <p>The hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.</p

The Tight Junction Associated Signalling Proteins ZO-1 and ZONAB Regulate Retinal Pigment Epithelium Homeostasis in Mice

Cell-cell adhesion regulates the development and function of epithelia by providing mechanical support and by guiding cell proliferation and differentiation. The tight junction (TJ) protein zonula occludens (ZO)-1 regulates cell proliferation and gene expression by inhibiting the activity of the Y-box transcription factor ZONAB in cultured epithelial cells. We investigated the role of this TJ-associated signalling pathway in the retinal pigment epithelium (RPE) in vivo by lentivirally-mediated overexpression of ZONAB, and knockdown of its cellular inhibitor ZO-1. Both overexpression of ZONAB or knockdown of ZO-1 resulted in increased RPE proliferation, and induced ultrastructural changes of an epithelial-mesenchymal transition (EMT)-like phenotype. Electron microscopy analysis revealed that transduced RPE monolayers were disorganised with increased pyknosis and monolayer breaks, correlating with increased expression of several EMT markers. Moreover, fluorescein angiography analysis demonstrated that the increased proliferation and EMT-like phenotype induced by overexpression of ZONAB or downregulation of ZO-1 resulted in RPE dysfunction. These findings demonstrate that ZO-1 and ZONAB are critical for differentiation and homeostasis of the RPE monolayer and may be involved in RPE disorders such as proliferative vitroretinopathy and atrophic age-related macular degeneration

Diffraction and reflection of antiplane shear waves in a cracked couple stress elastic material

We investigate the effect of a semi-infinite rectilinear crack on diffraction and reflection of antiplane shear waves in an elastic solid with microstructure. Waves are induced by moving shear traction vectors applied at the faces of the crack. The material behavior is described by the indeterminate theory of couple stress elasticity considering micro inertia. This elastic constitutive model accounts for the material microstructure and it is a special case of the micropolar theory; it was developed by Koiter [3] for the quasi-static regime and later extended by Eringen [1] to include dynamic effects. The full-field solution is obtained through integral transforms and the Wiener-Hopf technique [5] and it may be used as a bulding block to solve general wave propagation problems in a cracked half-space in antiplane deformation. The solution differs significantly from the classical result given in [2] for isotropic elastic materials. Indeed, unlike classical elasticity, antiplane shear Rayleigh waves are supported in couple stress materials [4]. A complicated wave pattern appears which consists of entrained waves extending away from the crack, reflected Rayleigh waves, localized waves irradiating from and body waves scattered by the crack-tip. Wave diffraction and interference brings an important contribution to the stress intensity factors originally presented in [6] in the static framework. Resonance is triggered when the applied loading is fed into the crack-tip at Rayleigh speed and this result is confirmed by the evaluation of the energy release rate

Structural diversity of angiotensin-converting enzyme : insights from structure-activity comparisons of two Drosophila enzymes.

The crystal structure of a Drosophila angiotensin-converting enzyme (ANCE) has recently been solved, revealing features important for the binding of ACE inhibitors and allowing molecular comparisons with the structure of human testicular angiotensin-converting enzyme (tACE). ACER is a second Drosophila ACE that displays both common and distinctive properties. Here we report further functional differences between ANCE and ACER and have constructed a homology model of ACER to help explain these. The model predicts a lack of the Cl–-binding sites, and therefore the strong activation of ACER activity towards enkephalinamide peptides by NaCl suggests alternative sites for Cl– binding. There is a marked difference in the electrostatic charge of the substrate channel between ANCE and ACER, which may explain why the electropositive peptide, MKRSRGPSPRR, is cleaved efficiently by ANCE with a low Km, but does not bind to ACER. Bradykinin (BK) peptides are excellent ANCE substrates. Models of BK docked in the substrate channel suggest that the peptide adopts an N-terminal β-turn, permitting a tight fit of the peptide in the substrate channel. This, together with ionic interactions between the guanidino group of Arg9 of BK and the side chains of Asp360 and Glu150 in the S2' pocket, are possible reasons for the high-affinity binding of BK. The replacement of Asp360 with a histidine in ACER would explain the higher Km recorded for the hydrolysis of BK peptides by this enzyme. Other differences in the S2' site of ANCE and ACER also explain the selectivity of RXPA380, a selective inhibitor of human C-domain ACE, which also preferentially inhibits ACER. These structural and enzymatic studies provide insight into the molecular basis for the distinctive enzymatic features of ANCE and ACER

Results in the treatment of paralytic calcaneus-valgus feet with the Westin technique

Between 1988 and 2003, 23 patients with paralytic calcaneus-valgus feet were submitted to the Westin procedure and 17 patients (25 feet) were re-evaluated. Nine patients were male and eight were female. The mean age at the surgical procedure was 8±5 years. The aetiology of paralysis was sequelae of poliomyelitis in 6 patients (8 feet) and of myelomeningocele in 11 patients (17 feet). The mean follow-up period was 6±6 years. The results were analysed clinically and radiographically considering the decrease of the retropulsion, the patient’s satisfaction, and the increase of the lateral tibiocalcaneal angle. Results were considered satisfactory when the patients showed a decrease of the retropulsion during gait, improvement of the gait pattern, and an increase of the tibiocalcaneal angle. As an overall result, 16 patients (94.2%) were satisfied and 1 patient (two feet) dissatisfied with the outcome. The increase of the tibiocalcaneal angle was significant for the myelomeningocele patients (P=0.001), but not for poliomyelitis (P=0.053). No statistical relation between the follow-up period and the increase of the tibiocalcaneal angle was found (r=0.04). The authors concluded that the Westin procedure is a good technique for the treatment of paralytic calcaneus valgus feet with myelomeningocele