Purpose Design an efficient CEST scheme for exchange‐dependent images with high contrast‐to‐noise ratio. Theory Reassembled saturation transfer (REST) signals were defined as r.Z = r.Z ref ‐ r.Z CEST and the reassembled exchange‐dependen magnetization transfer ratio r.MTR Rex = r.1/ Z ref ‐ r.1/ Z CEST , utilizing the averages over loosely sampled reference frequency offsets as Z ref and over densely sampled target offsets as Z CEST . Using r.MTR Rex measured under 2 B 1,sat values, exchange rate could be estimated. Methods The REST approach was optimized and assessed quantitatively by simulations for various exchange rates, pool concentration, and water T 1 . In vivo evaluation was performed on ischemic rat brains at 7 Tesla and human brains at 3 Tesla, in comparison with conventional asymmetrical analysis, Lorentzian difference (LD), an MTR Rex_ LD. Results For a broad choice of ranges and numbers, Δr.Z and r.MTR Rex exhibited comparable quantification features with conventional LD and MTR Rex _LD, respectively, when B 1,sat ≤ 1 μT. The subtraction of 2 REST values under distinct B 1,sat values showed linear relationships with exchange rate and obtained immunity to field inhomogeneity and variation in MT and water T 1 . For both rat and human studies, REST images exhibited similar contrast distribution to MTR Rex _LD, with superiority in contrast‐to‐noise ratio and acquisition efficiency. Compared with MTR Rex _LD, 2‐B 1,sat subtraction REST images displayed better resistance to B 1 inhomogeneity, with more specific enhanced regions. They also showed higher signals for amide than for nuclear Overhauser enhancement effect in human brain, presumably reflecting the higher increment from faster‐exchanging species as B 1,sat increased. Conclusion Featuring high contrast‐to‐noise ratio efficiency, REST could be a practical exchange‐dependent approach readily applicable to either retrospective Z‐spectra analysis or perspective 6‐offset acquisition.
Objective To explore the relationship between the proliferation of neural stem cells (NSCs)and the expression of β-catenin protein in neonate rats with hypoxic ischemic brain damage (HIBD) after hyperbaric oxygen (HBO) therapy. Methods One hundred and eighty Sprague-Dawley rats aged 7 days were randomly divided into a normal control group (CON) , a HIBD model group and a HBO treatment group. The HIBD model was induced using Rice's method. Beginning 3h after the HIBD, HBO was administered to the HBO treatment group at 2 atmospheres for 60 min, once daily for 7 days. The HIBD model group was not given any treatment. The expression of nestin/β-catenin protein in the subventricular zone of the ischemic brain was double-stained for immunofluorescence and analyzed by confocal scanning microscopy dynamically at 3 hours, 21 hours, and then on the 3rd, 5th, 7th and 14th day of HBO therapy. The expression of whole cell β-catenin and nuclear β-catenin protein in the left brain were also examined by Western blotting at these 6 time points. Linear correlation was used to analyze the correlation between β-catenin and nestin protein. Results The expression of β-catenin protein in NSCs increased initially at the 21st hour after HBO therapy in the model group and the HBO group as compared with the normal control group.β-catenin protein in the model group reached a higher level, though there was no significant difference between model group and the HBO group. At the 5th day of HBO therapy β-catenin protein in the HBO group had reached a significantly higher level than in the model group. At the 14th day the average expression of β-catenin in the HBO group began to decrease. The expression of nestin protein began to increase 21 hours after HBO therapy began, and it peaked at the 7th day of HBO therapy and then decreased. In the HBO group the increase in nestin protein was linearly correlated with that of β-catenin protein. The whole cell β-catenin protein and β-catenin nucleic protein readings increased initially by the 21st hour of HBO therapy and by the 5th day were significantly higher than the levels in the model group. Conclusion HBO treatment is capable of stimulating the proliferation of NSCs in HIBD neonate rats.The proliferation of NSCs is correlated with the activation of β-catenin protein.
Key words:
Hyperbaric oxygen; Hypoxic-ischemic brain damage; Neural stem cells; β-catenin
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) had shown potential in sensing pH changes that occurs early in ischemic stroke. However, detection of mild acidosis is still challenging. To enhance CEST detection for ischemia, we proposed a quantification approach using the residual of inversed Z-spectra, i.e. MTR RexVOPVP = 1/Z exp -1/Z ref , where the reference Z-spectra Z ref was calculated using our previously developed Voxel-wise Optimization of Pseudo Voigt Profile (VOPVP). Simulations were performed at two different exchange rates of amide, representing different pH values. Among all tested quantification methods, including MTR asym , Lorentzian Difference (LD), VOPVP residual (ZVOPVP residual), the analytical solution and MTR RexOPVP , MTR RexVOPVP exhibited the largest difference between the two exchange rates. In vivo CEST-MRI was performed at 7 Tesla in rat brain, at 2 hours after transient ischemia by middle cerebral artery occlusion. Firstly, Z-spectra images were assessed at multiple offsets using histogram analysis, with 3.5 and -3.5 ppm exhibiting significant changes between normal rats and stroke rats (n = 5 each). For all stroke rats, MTR RexVOPVP images (3.5 ppm) exhibited a large area of hypointensity in the lesion hemisphere. In contrast, MTR asym and the three-offsets method failed in detecting such changes, particularly for rats with little changes on T 2w and DWI images. Among all tested methods, MTR RexVOPVP achieved the highest contrast-to-noise ratio between lesion striatum and the contralateral. For amide, amine and NOE, Z residualVOPVP and MTR RexVOPVP showed significant reduced signals in lesions compared to the contralateral, indicating lower pH with slower exchange. But Z-spectra and MTRasym signal did not show such difference. At later time points (6 hrs and 24 hrs), all methods displayed contrast between two hemispheres and MTR RexVOPVP still show the largest contrast between the two hemisphere. Histology confirmed the edema and other damage in the ipsilateral hemisphere at 2 hours post transient ischemia. In summary, MTR RexVOPVP may enhance CEST detection for ischemia.
Background: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. Methods: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl-- cotransporter 1; NKCC1) was performed. Results: rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. Conclusions: MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI.
Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.
5d, a novel analogue of the racemic 3-n-butylphthalide (NBP), has been reported for its free radical scavenging activity in vitro and preventive neuroprotection in vivo. Nevertheless, the mechanism by which 5d attenuated ischemia/reperfusion (I/R) injury is still unknown. Our results showed that 5d significantly increased CK2 activity as well as CK2α and 2α' protein levels after I/R injury. Besides, 5d suppressed the translocation of cytosolic p47phox and Rac1 to the membrane, decreased NOX4 expression and ROS generation. Furthermore, 5d blocked the dissociation between CK2α and Rac1 so as to decrease NADPH oxidase activity. Based on these findings, we propose that the neuroprotective effect of 5d is due to an increase of CK2 activity, which blocks I/R-induced dissociation between CK2α and Rac1, decreases NADPH oxidase activity, inhibits ROS production and finally realizes the neuroprotection of I/R. These findings point to that 5d might be considered an attractive candidate for further studies in ischemic stroke.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)