Activation of p38 MAPK hinders the reactivation of visual cortical plasticity in adult amblyopic mice.

OBJECTIVE: To investigate the impact of p38 mitogen-activated protein kinase (MAPK) signaling on reactivating visual cortical plasticity in adult amblyopic mice. MATERIALS AND METHODS: Reverse suture (RS), environment enrichment (EE), and combined with left intracerebroventricular injection of p38 MAPK inhibitor (SB203580, SB) or p38 MAPK agonist (dehydrocorydaline hydrochloride, DHC) were utilized to treat adult amblyopic mice with monocular deprivation (MD). The visual water task, visual cliff test, and Flash visual-evoked potential were used to measure the visual function. Then, Golgi staining and transmission electron microscopy were used to assess the reactivation of structural plasticity in adult amblyopic mice. Western blot and immunohistochemistry detected the expression of ATF2, PSD-95, p38 MAPK, and phospho-p38 MAPK in the left visual cortex. RESULTS: No statistically significant difference was observed in the visual function in each pre-intervention group. Compared to pre-intervention, the visual acuity of deprived eyes was improved significantly, the impairment of visual depth perception was alleviated, and the P wave amplitude and C/I ratio were increased in the EE + RS, the EE + RS + SB, and the EE + RS + DMSO groups, but no significant difference was detected in the EE + RS + DHC group. Compared to EE + RS + DHC group, the density of dendritic spines was significantly higher, the synaptic density of the left visual cortex increased significantly, the length of the active synaptic zone increased, and the thickness of post-synaptic density (PSD) thickened in the left visual cortex of EE + RS, EE + RS + SB, and EE + RS + DMSO groups. And that, the protein expression of p-p38 MAPK increased while that of PSD-95 and ATF2 decreased significantly in the left visual cortex of the EE + RS + DHC group mice. CONCLUSION: RS and EE intervention improved the visual function and synaptic plasticity of the visual cortex in adult amblyopic mice. However, activating p38 MAPK hinders the recovery of visual function by upregulating the phosphorylation of p38 MAPK and decreasing the ATF2 protein expression.

Regulatory role of the p38 MAPK/ATF2 signaling pathway in visual function and visual cortical plasticity in mice with monocular deprivation.

BACKGROUND: This study aimed to examine the role of the p38 mitogen-activated protein kinase (MAPK)/ activating transcription factor 2 (ATF2) signaling in visual function impairment and visual cortical plasticity in mice with monocular deprivation (MD). METHODS: Visual behavioral tests, including visual water task, visual cliff test, and flash visual evoked potential, were performed on each group. We studied the density of dendritic spines and the synaptic ultrastructure by Golgi staining and transmission electron microscope. We performed Western blot and immunohistochemistry and detected the expression of ATF2, PSD-95, p38 MAPK, and phosphor-p38 MAPK in the left visual cortex. RESULTS: In the MD + SB group, the visual acuity in deprived eyes substantially improved, the impairment of visual depth perception was alleviated, and the P wave amplitude and C/I ratio increased. The density of dendritic spines and the numerical density of synapses increased significantly, the width of the synaptic cleft decreased significantly, and the length of the active synaptic zone and the thickness of post-synaptic density (PSD) increased substantially. The protein expression of phosphor-p38 MAPK decreased, whereas that of PSD-95 and ATF2 increased significantly. CONCLUSIONS: Inhibiting the phosphorylation of p38 MAPK and negative feedback upregulated ATF2 expression, alleviated damage to visual function, and protected against synaptic plasticity in mice with MD.

Amblyopia: progress and promise of functional magnetic resonance imaging.

Amblyopia is a neurodevelopmental disorder characterized by functional deficits in the visual cortex. Functional magnetic resonance imaging (fMRI) is the most commonly used neuroimaging technique for investigating amblyopia. Herein, we systematically searched a PubMed database from inception to December 2021 to highlight the current progress and promises about fMRI technology in amblyopia; amblyopia's neural mechanism, the comparison of different types of amblyopia, and the evaluation of the therapeutic effect were explored. Relevant articles published in English and appropriate cross-references were considered for inclusion, including basic studies, imaging techniques, clinical diagnostic and therapeutic studies, case series, and reviews.

Preoperative prediction of intra-tumoral tertiary lymphoid structures based on CT in hepatocellular cancer.

PURPOSE: Intra-tumoral tertiary lymphoid structures (TLSs) are associated with a favorable prognosis for patients with hepatocellular carcinoma (HCC). We aimed to identify image features related to TLSs and develop a nomogram for preoperative noninvasive prediction of intra-tumoral TLSs. METHODS: This retrospective study enrolled patients with HCC who underwent contrast-enhanced computed tomography before surgery between January 2014 and September 2020. Two radiologists retrospectively and independently reviewed the CT imaging features, and interobserver agreement was assessed. Univariable and multivariable logistic regression analyses were applied to investigate clinical laboratory data and imaging features related to TLSs. A regression-based predictive model and nomogram were constructed using the identified predictors. Nomogram diagnostic performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curves, and validated using 5-fold cross-validation. RESULTS: Ninety-three of the 142 HCCs were TLS + HCCs. Multivariable analyses identified intratumor arteries (odds ratio [OR]: 0.23; 95% confidence interval [CI]: 0.07-0.63; p = 0.007), intratumor hemorrhage (OR: 0.08; 95% CI: 0.01-0.50; p = 0.012), positive HBsAg or HCVAB status (OR: 4.52; 95% CI: 1.65-13.29; p = 0.004), platelet count (≥186.5 × 109 /L, OR: 0.38; 95% CI: 0.16-0.86; p = 0.022), and aspartate transaminase level (≥33.2 IU/l, OR: 0.24; 95% CI: 0.09-0.59; p = 0.003) as independent predictors of intra-tumoral TLSs. AUC of the regression-based model was 0.79 (95% CI:0.72-0.86) and average AUC at 5-fold cross-validation was 0.75 (95% CI: 0.71-0.80). CONCLUSIONS: CT-based nomogram is promising for preoperative prediction of intra-tumoral TLS in HCC.