Regeneration after severe spinal cord injury cannot occur naturally in mammals. Transplanting stem cells to the injury site is a highly promising method, but it faces many challenges because it relies heavily on the microenvironment provided by both the lesion site and delivery material. Although mechanical properties, biocompatibility, and biodegradability of delivery materials have been extensively explored, their permeability has rarely been recognized. Here, a DNA hydrogel is designed with extremely high permeability to repair a 2 mm spinal cord gap in Sprague–Dawley rats. The rats recover basic hindlimb function with detectable motor‐evoked potentials, and a renascent neural network is formed via the proliferation and differentiation of both implanted and endogenous stem cells. The signal at the lesion area is conveyed by, on average, 15 newly formed synapses. This hydrogel system offers great potential in clinical trials. Further, it should be easily adaptable to other tissue regeneration applications.

Background: The human brain has an extraordinary ability to functionally change or reorganize its structure in response to disease. The aim of this study is to assess the structural and functional plasticity of contralesional medial temporal lobe (MTL) in patients with unilateral MTL glioma.Methods: Sixty-eight patients with unilateral MTL glioma (left MTL glioma, n = 33; right MTL glioma, n = 35) and 40 healthy controls were recruited and scanned with 3D T1 MRI and rest-fMRI. We explored the structure of the contralesional MTL using voxelbased morphometry (VBM) and assessed the memory networks of the contralesional hemisphere using resting-state functional connectivity (rs-FC). The association between FC and cognitive function was assessed with partial correlation analysis.Results: Compared with healthy controls, both patient groups exhibited (1) a large cluster of voxels with gray matter (GM) volume decrease in the contralesional MTL using region of interest (ROI)-based VBM analysis (cluster level p < 0.05, FDR corrected); and (2) decreased intrahemispheric FC between the posterior hippocampus (pHPC) and posterior cingulate cortex (PCC) (p < 0.01, Bonferroni corrected). Intrahemispheric FC between the pHPC and PCC was positively correlated with cognitive function in both patient groups.Conclusion: Using multi-modality brain imaging tools, we found structural and functional changes in the contralesional MTL in patients with unilateral MTL glioma. These findings suggest that the contralesional cortex may have decompensation of structure and function in patients with unilateral glioma, except for compensatory structural and functional adaptations. Our study provides additional insight into the neuroanatomical and functional network changes in the contralesional cortex in patients with glioma.

Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas (GHPA) is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal surgery. Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in tumor angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed that the expression level of EGFL7 and p-EGFR in invasive GHPA was much higher than that of non-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR (p-EGFR). Noticeably, EGFL7 knockdown significantly inhibited activation of EGFR signaling cascades, including p-ERGR, p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478, significantly suppressed migration and invasion of GH3 and GT1-1 cells. In summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR signaling pathway and plays an important role in migration and invasion of invasive GHPA.

BackgroundPrior investigations of language functions have focused on the response profiles of particular brain regions. However, the specialized and static view of language processing does not explain numerous observations of functional recovery following brain surgery. To investigate the dynamic alterations of functional connectivity (FC) within language network (LN) in glioma patients, we explored a new flexible model based on the neuroscientific hypothesis of core-periphery organization in LN.MethodsGroup-level LN mapping was determined from 109 glioma patients and forty-two healthy controls (HCs) using independent component analysis (ICA). FC and mean network connectivity (mNC: l/rFCw, FCb, and FCg) were compared between patients and HCs. Correlations between mNC and tumor volume (TV) were calculated.ResultsWe identified ten separate LN modules from ICA. Compared to HCs, glioma patients showed a significant reduction in language network functional connectivity (LNFC), with a distinct pattern modulated by tumor position. Left hemisphere gliomas had a broader impact on FC than right hemisphere gliomas, with more reduced edges away from tumor sites (p=0.011). mNC analysis revealed a significant reduction in all indicators of FC except for lFCw in right hemisphere gliomas. These alterations were associated with TV in a double correlative relationship depending on the tumor position across hemispheres.ConclusionOur findings emphasize the importance of considering the modulatory effects of core-periphery mechanisms from a network perspective. Preoperative evaluation of changes in LN caused by gliomas could provide the surgeon a reference to optimize resection while maintaining functional balance.

Background and Objective: Large suprasellar tumors often compress the optic chiasm and give rise to visual impairment. Most patients have significantly improved visual function at 1 to 4 months after chiasmal decompression surgery, and only a few individuals regain normal vision at 1 week after surgery. How the recovery of visual function in these patients affects the visual cortex is not fully understood. In this study, we aimed to investigate alterations in brain functional connectivity (FC) in suprasellar tumor patients with visual improvement using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: This longitudinal study was conducted on 13 suprasellar tumor patients who had ophthalmological examinations and rs-fMRI at the following time points: within 1-week preoperation (Pre-op), 1-week postoperation (Post-1w) and 1-month postoperation (Post-1m). The visual impairment score (VIS), local functional correlation (LCOR) and FC values were subjected to one-way ANOVA. Pearson correlation coefficients between changes in the LCOR and clinical factors were calculated. Results: The VIS was significantly decreased at both Post-1w and Post-1m compared to that at Pre-op. Whole-brain analysis of LCOR values showed that the left V1 (primary occipital cortex) was increased significantly at Post-1m compared to that at Pre-op (p < 0.05, FDR corrected). ROI analysis exhibited a significant negative correlation between the LCOR and VIS changes at Post-1m compared to those at Pre-op (p < 0.05, r =-0.60). FC analysis within the visual network showed that the FC strengths were significantly increased between the left V5 and the left V4, right V3a, left V3, left V2d, and right V5 at Post-1m compared to those at Pre-op (p < 0.05, FDR corrected). Additionally, the FC strengths were significantly increased between the left V5 and the left V1, right orbital-frontal gyrus and left posterior supramarginal gyrus at the whole-brain network level at Post-1m compared to those at Pre-op (p < 0.05, FDR corrected). Conclusions: Postoperative visual improvement can be reflected by the increased FC of the visual cortex at Post-1w and Post-1m, especially at Post-1m. The LCOR value of the left V1 was associated with improved visual outcomes and may be used to objectively assess early visual recovery after chiasmal decompression at Post-1m.

Poor prognosis is often expected after the treatment of intracerebral haemorrhage (ICH) when the approach lacks effective neuroprotective interventions. Minocycline (Mino) is a promising clinical neuroprotective candidate for acute ICH therapy that mainly inhibits activation of microglia/macrophages. However, to address iron neurotoxicity, ferroptosis, and oxidative stress‐induced multiple neuroinjury mechanisms, the neuroprotective effect of minocycline still urgently needs to be enhanced. To address this issue, procyanidins (PACs), typical natural polyphenols, is used to improve the neuroprotective effect of Mino by constructing PACs‐Mino nanoparticles (NPs) using 3‐aminophenylboronic acid as the crosslinker. The yielding NPs possessed improved antioxidant and iron‐removing capacities in vitro. More importantly, PACs‐Mino NPs exerted excellent therapeutic effects on ICH, showing improved neuroprotective activity and resulting in neurobehavioral recovery, in an in vitro cellular model and an in vivo ICH rat model. This study can provide a general strategy that uses natural polyphenols to boost the performance of drugs for ICH treatment, and the results may be further extended to other injuries of the central nervous system, such as brain injury and spinal cord injury.

Severe spinal cord injury (SCI) leads to permanent, complete paraplegia and places considerable mental and economic burdens on patients, compared with mild to moderate SCI. However, the dose-related effects of the neural stem/precursor cell (NSPC) transplantation on the injury microenvironment, NSPC survival, axonal growth, neuronal distribution, the composition of neurons, oligodendrocytes, and astrocytes in the lesion area and functional recovery have not yet been quantitatively evaluated in the context of severe SCI. In our study, we acutely transplanted 2.5×104 or 1.5×105 NSPCs/μl into the site of transection SCI. We found that high-dose NSPC transplantation exerted immunomodulatory and neuroprotective effects in the acute phase of severe SCI. In addition, one week later, a remarkable positive relationship was observed between the transplantation dose and the number of surviving NSPCs in severe SCI. At 8 weeks postgrafting, subjects that received the higher cell dose exhibited abundant nerve regeneration, extensive neuronal distribution, increased proportions of neurons and oligodendrocytes, and nascent functional neural network formation in the lesion area. Notably, a significant functional recovery was also observed. Our data suggest that it is important to consider potential dose-related effects on donor cell survival, neuronal distribution, and locomotor recovery in the development of preclinical NSPC transplantation therapy for severe SCI.

Growth hormone (GH) and its anabolic mediator, insulin-like growth factor-1 (IGF-1), have a critical role in the central nervous system. However, their detailed roles in the adult human brain are not clear. In this study, structural MRIs of 48 patients with GH-secreting pituitary adenoma (GH-PA), 48 sex-and age-matched clinical Non-Functional pituitary adenoma patients (NonFun-PA) and healthy controls (HCs) were assessed using voxelbased morphometry (VBM) and region-based morphometry (RBM). Correlation analyses helped determine the relationships between serum hormone levels and brain structure. The whole-brain gray matter volume (GMV) and white matter volume (WMV) significantly increased at the expense of cerebrospinal fluid volume (CSFV) in GH-PA (Bonferroni corrected, p<0.01). The increase in GMV and reduction in CSFV were significantly correlated with serum GH/IGF-1 levels (p<0.05). VBM showed significant correlations of the GMV/WMV alteration pattern between GH-PA vs HCs and GH-PA vs NonFun-PA and widespread bilateral clusters of significantly increased GMV and WMV in GH-PA (pFDR<0.05). RBM showed obviously increased GMV/WMV in 54 of 68 brain regions (p<0.05) in GH-PA compared to HCs. Our results provide imaging evidence that serum GH/IGF-1 contributes to brain growth, which may be a potential treatment option for neurodegenerative disorders and brain injury in humans.