How I do it? Resection of left ventricular central neurocytoma via trans-sulcal approach.

BACKGROUND: The management of lateral ventricle tumors requires a balance between maximizing safe resection and preserving neurological function. METHOD: The authors present a successful case of a left lateral ventricular central neurocytoma resection. The trans-superior frontal sulcus approach was employed, providing a safe corridor while minimizing damage to the surrounding neuroanatomy. The use of an endoscope further facilitated the procedure, enabling the confirmation of complete tumor removal and the preservation of deep venous drainage and periventricular structures. CONCLUSION: This case highlights the utility of the trans-sulcal approach and the benefits of endoscopic assistance in the management of lateral ventricle tumors.

Combination of Conventional EVD and Ommaya Drainage for Intraventricular Hemorrhage (IVH).

Background: The effect of Ommaya reservoirs on the clinical outcomes of patients with intraventricular hemorrhage (IVH) remains unclear. Objective: We aimed to determine the effect of combining the Ommaya reservoir and external ventricular drainage (EVD) therapy on IVH and explore better clinical indicators for Ommaya implantation. Methods: A retrospective analysis was conducted on patients diagnosed with IVH who received EVD-Ommaya drainage between January 2013 and March 2021. The patient population was divided into two groups: the Ommaya-used group, comprising patients in whom the Ommaya drainage system was activated post-surgery, and the Ommaya-unused group, comprising patients in whom the system was not activated. The study analyzed clinical, imaging, and outcome data of the patient population. Results: A total of 123 patients with IVH were included: 75 patients in the Ommaya-used group and 48 patients in the Ommaya-unused group. The patients in the Ommaya-used group showed a lower 3-month GOS than those in the Ommaya-unused group (p<0.0001). The modified Graeb scale (mGS) in the Ommaya-unused group was significantly lower than that in the Ommaya-used group before the operation (p<0.01) but not after surgery (p>0.05). The GCS in the Ommaya-unused group was significantly lower than that in the other group, and there was a close correlation between the GCS and 3-month GOS (p<0.0001). The GCS score showed significance in predicting the use of Ommaya (p<0.001). Conclusion: The study demonstrated that combining EVD and Ommaya drainage was a safe and feasible treatment for IVH. Additionally, preoperative GCS was found to predict the use of Ommaya drainage in subsequent treatment, providing valuable information for pre-surgery decision-making.

Apelin-Overexpressing Neural Stem Cells in Conjunction with a Silk Fibroin Nanofiber Scaffold for the Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function.

Engineered Extracellular Vesicle-Delivered CRISPR/CasRx as a Novel RNA Editing Tool.

Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide-optimized and EVs-delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)-triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short-acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases.

PS-NPs Induced Neurotoxic Effects in SHSY-5Y Cells via Autophagy Activation and Mitochondrial Dysfunction.

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood-brain barrier and increase the incidence of neurodegenerative diseases. However, information relating to the pathogenic molecular mechanism is still unclear. This study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious mitochondrial damages, as evidenced by inhibited cell proliferation, increased lactate dehydrogenase release, stimulated oxidative stress responses, elevated Ca2+ level and apoptosis, and reduced mitochondrial membrane potential and adenosine triphosphate levels. The increased release of cytochrome c and the overexpression of apoptosis-related proteins apoptotic protease activating factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In addition, the upregulation of autophagy markers light chain 3-II (LC3-II), Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial damages caused by oxidative stress could potentially be involved in the pathological mechanisms for PS-NP-induced neurodegenerative diseases.

Surgical Resection of a Third Ventricle Nongerminomatous Germ Cell Tumor: Two-Dimensional Operative Video.

Surgical resection of a pineal tumor growing into the third ventricle is difficult owing to the complex neurovascular structures, and nongerminomatous germ cell tumor is the most common malignant tumor in pediatric patients. Removing the tumor efficiently with minimal blood loss while protecting the surrounding neurovascular structure is challenging. We present a surgical case of a 9-year-old patient with a third ventricle nongerminomatous germ cell tumor (Video). Mass effect of the tumor or acute hydrocephalus is the possible reason for the coma. In this case, the reason of coma may be mass effect of the tumor, not the acute hydrocephalus. Informed consent was obtained from the patient's guardian. Intraoperatively we used a modified right head-up park bench position and a linear incision. The right occipital bone flap was designed to cross the superior sagittal sinus and transverse sinus. The primary surgical approach was the occipital transtentorial approach; an alternative was the supracerebellar infratentorial approach. After cutting the tentorium, a spatula was applied to retract the cerebellum and incised tentorium, with no extra brain retraction on the occipital lobe to minimize visual disturbance. The quadrigeminal cistern was opened, and the tumor was yellowish with heterogeneous consistency. Instead of rushing into the tumor debulking, we paid more attention to devascularization of the tumor from bilateral posterior medial choroidal arteries as much as possible. After debulking using an ultrasound aspirator, the tumor was removed in a piecemeal fashion, and the surgical field was inspected using an endoscope for any residue.

Neural Stem Cells Therapy for Ischemic Stroke: Progress and Challenges.

Ischemic stroke, with its high morbidity and mortality, is the most common cerebrovascular accident and results in severe neurological deficits. Despite advances in medical and surgical intervention, post-stroke therapies remain scarce, which seriously affects the quality of life of patients. Over the past decades, stem cell transplantation has been recognized as very promising therapy for neurological diseases. Neural stem cell (NSC) transplantation is the optimal choice for ischemic stroke as NSCs inherently reside in the brain and can potentially differentiate into a variety of cell types within the central nervous system. Recent research has demonstrated that NSC transplantation can facilitate neural recovery after ischemic stroke, but the mechanisms still remain unclear, and basic/clinical studies of NSC transplantation for ischemic stroke have not yet been thoroughly elucidated. We thus, in this review, provide a futher understanding of the therapeutic role of NSCs for ischemic stroke, and evaluate their prospects for future application in clinical patients of ischemic stroke.

Downregulation of Thbs4 caused by neurogenic niche changes promotes neuronal regeneration after traumatic brain injury.

OBJECTIVE: Following brain injury, the neurogenic niche provides a permissive cue for iatrogenesis rather than neurogenesis; reactive astrocytes play essential roles in orchestrating this process, markedly forming a glial scar around the area of damaged brain tissue. The objective of this study was to alter the neurogenic niche at the injured cortex and study its impact on neurogenesis. METHODS: We constructed a stromal cell-derived factor 1 (SDF-1) gradient matrix to attract reactive astrocytes to the glial scar core. RESULTS: SDF-1 reacted with the astrocytes in the injured site. By changing the neurogenic niche of the injured part of the brain after traumatic brain injury (TBI), SDF-1 downregulated thrombospondin 4 (Thbs4) promoting neuronal cell regeneration and playing a beneficial role in nerve function recovery after brain injury. DISCUSSION: The matrix we created in this study could attract and interact with reactive glial cells and, thus, we called it a glial pump. Using the glial pump, we identified a new mechanism of brain injury repair and neuronal regeneration after TBI, which relied on Thbs4 downregulation after the altered neurogenic niche promoted neuronal regeneration and functional recovery.

Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier.

To maintain brain homeostasis, a unique interface known as the blood-brain barrier (BBB) is formed between the blood circulation and the central nervous system (CNS). Major facilitator superfamily domain-containing 2a (Mfsd2a) is a specific marker of the BBB. However, the mechanism by which Mfsd2a influences the BBB is poorly understood. In this study, we demonstrated that Mfsd2a is essential for sphingosine-1-phosphate (S1P) export from endothelial cells in the brain. We found that Mfsd2a and Spinster homolog 2 (Spns2) form a protein complex to ensure the efficient transport of S1P. Furthermore, the S1P-rich microenvironment in the extracellular matrix (ECM) in the vascular endothelium dominates the formation and maintenance of the BBB. We demonstrated that different concentrations of S1P have different effects on BBB integrity. These findings help to unravel the mechanism by which S1P regulates BBB and also provide previously unidentified insights into the delivery of neurological drugs in the CNS.

Using apelin-based synthetic Notch receptors to detect angiogenesis and treat solid tumors.

Angiogenesis is a necessary process for solid tumor growth. Cellular markers for endothelial cell proliferation are potential targets for identifying the vasculature of tumors in homeostasis. Here we customize the behaviors of engineered cells to recognize Apj, a surface marker of the neovascular endothelium, using synthetic Notch (synNotch) receptors. We designed apelin-based synNotch receptors (AsNRs) that can specifically interact with Apj and then stimulate synNotch pathways. Cells engineered with AsNRs have the ability to sense the proliferation of endothelial cells (ECs). Designed for different synNotch pathways, engineered cells express different proteins to respond to angiogenic signals; therefore, angiogenesis can be detected by cells engineered with AsNRs. Furthermore, T cells customized with AsNRs can sense the proliferation of vascular endothelial cells. As solid tumors generally require vascular support, AsNRs are potential tools for the detection and therapy of a variety of solid tumors in adults.

Shikonin ameliorates D-galactose-induced oxidative stress and cognitive impairment in mice via the MAPK and nuclear factor-κB signaling pathway.

Oxidative stress acts as the major causative factor for various age-associated neurodegenerative diseases, triggering cognitive and memory impairments. In the present study, the underlying neuroprotective mechanism governing how shikonin acts against D-galactose (D-gal)-induced memory impairment, neuroinflammation and neuron damage was examined. The results revealed that chronic administration of D-gal [150 mg/kg intraperitoneally (i.p.)] in mice caused cognitive and memory impairments, as determined by Morris water-maze test. Shikonin treatment, however, alleviated D-gal-induced memory impairment and reversed the D-gal-induced neural damage and apoptosis. Furthermore, western blotting and the results of morphological analysis revealed that shikonin treatments markedly reduced D-gal induced neuroinflammation through inhibition of astrocytosis as determined by glial fibrillary acidic protein (GFAP) detection, and downregulating other inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6. Moreover, shikonin treatment led to inhibition of the activation of nuclear factor-κB (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs), preventing neurodegeneration. Hence, taken together, the results of the present study suggested that shikonin attenuated D-gal-induced memory impairment, neuroinflammation and neurodegeneration, possibly via the NF-κB/mitogen-activated protein kinase (MAPK) pathway. Our data suggest that shikonin could be a promising, endogenous and compatible antioxidant candidate for age-associated neurodegenerative diseases, including Alzheimer's disease.

A Prevascularization Strategy Using Novel Fibrous Porous Silk Scaffolds for Tissue Regeneration in Mice with Spinal Cord Injury.

Spinal cord injury (SCI) represents an extremely debilitating condition for which no efficacious treatment is available. Because spinal cord does not have satisfactory capacity for revascularization after injury, it seems to be a promising way to modulate the lesion environment by reperfusion to promote a regenerative phenotype. Although engineered scaffolds provide a platform to deliver therapeutic cells and neurotrophic factors, slow and insufficient vascularization of large tissue constructs negatively impacts the survival and function of these transplanted cells. In this study, we cocultured our fibrous porous silk scaffold (FPSS) with ADAMTS13-overexpressing human umbilical vein endothelial cells (HUVECs) in vitro and transplanted this prevascularized construct into an SCI mouse model. The prevascularized system exhibited a tube-like structure in vitro, promoted vascular infiltration and microvascular network formation after transplantation, and recruited more neural cells to the lesion site. Twenty-eight days later, behavioral analysis showed that locomotor recovery was significantly improved in treated animals compared with control animals. Taken together, our results suggest that the FPSS-HUVECs system promoted neovascularization, guided axon growth at the injury site, and improved the microenvironment. Therefore, this prevascularization system may provide a better therapeutic option for SCI.

Regulation of autophagy in mesenchymal stem cells modulates therapeutic effects on spinal cord injury.

Transplantation with mesenchymal stem cells (MSCs) has shown beneficial effects in treating spinal cord injury. Autophagy is an evolutionarily conserved process of degradation and recycling of cellular components that plays an important role in tissue homeostasis and cellular survival. Whether regulating autophagy in MSCs may affect their therapeutic potential in spinal cord injury repair has not yet been determined. In this study, autophagy was inhibited in MSCs with lentiviruses expressing short hairpin RNA (shRNA) to knock down Becn-1 expression, and autophagy was upregulated in MSCs under nutrient starvation. These MSCs were then labelled with Hoechst and applied to spinal cord-injured rats to evaluate their therapeutic effects. After transplanting MSCs into rats with spinal cord injuries, functional recovery, immunohistochemistry, and remyelination analyses were performed. After inducing autophagy, the MSCs exhibited an accumulation of LC3-positive autophagosomes in the cytoplasm. The expression levels of neurotrophic factors, including vascular endothelial growth factor and brain derived neurotrophic factor, were significantly higher in autophagic MSCs than normal MSCs. The in vivo study showed that more labelled MSCs migrated to the lesion site after induction of autophagy. Inducing autophagy in MSCs promoted functional recovery after spinal cord injury, whereas functional recovery was weak after inhibiting autophagy in MSCs. In contrast to the autophagy inhibition group, transplanting autophagic MSCs exhibited a greater positive impact on axon regeneration, growth of serotonergic fibers, blood vessel regeneration, and myelination, indicating a multifactorial contribution to spinal cord injury repair. These results suggest that autophagy plays important roles in MSCs during spinal cord injury repair. Regulation of autophagy in MSCs before in vivo transplantation may be a potential therapeutic interventional strategy for spinal cord injury.

Aloin attenuates cognitive impairment and inflammation induced by d-galactose via down-regulating ERK, p38 and NF-κB signaling pathway.

Oxidative stress is considered as major culprit for neurodegenerative diseases and triggers cognitive and memory impairments. The present study mainly aimed to study the protective effects and underlying mechanisms of aloin on d-galactose (d-gal) induced ageing mice. Our results demonstrated that chronic administration of d-gal (150 mg kg-1) in mice caused spontaneous and cognitive impairments, as determined by open-field test and Morris water-maze test. Aloin treatment significantly ameliorated histopathological damage, attenuated the microglia activation and reduced levels of inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in the hippocampus. Moreover, it effectively suppressed the level of reactive oxygen species (ROS) and increased antioxidant enzymes activities. Further data showed that these protective effects were accompanied by inhibition of the activation of nuclear factor kappa B and the phosphorylation of p38 and ERK. In conclusion, the present study suggests that aloin can ameliorate d-gal induced oxidative stress, cognitive impairment and inflammation, possibly via mediating the ERK, p38 and NF-κB signaling pathways.

Cell Labeling with Cy3 through DNA Hybridization for Assessing Neural Stem Cells Survival and Differentiation.

Neural stem cells (NSCs) have been attractive donor sources for cell therapy in traumatic brain injuries (TBI). Monitoring the fate of transplanted cells, including the survival and differentiation, will provide vital information to assess the outcome during the therapy time course. However, the current labeling methods are based on the principles of cell endocytosis, demanding relatively high fluorescent probes concentration and long incubation time, which may affect the proliferation and differentiation of transplanted cells. In our study, an efficient and relatively fast labeling strategy for NSCs with Cy3 based on DNA hybridization was proposed for monitoring the fate of transplanted cells. The oligo[dA]20 conjugated with Cy3 was anchored on NSCs which had modified with oligo[dT]20 via the oligo[dT]20-oligo[dA]20 hybridization. This labeling system did not affect the viability of labeled NSCs. After implantation of labeled NSCs into the brain, immunohistology demonstrated implanted cells were able to survive and differentiate into mature neural cells as long as one month. In conclusion, the DNA hybridization system can be used as an efficient cell labeling method in cell therapy.

Schwannoma of the Fourth Ventricle: Report of Two Cases and Review of Literature.

BACKGROUND: Schwannomas have been reported in several unusual intracranial locations. Here we report 2 cases of extremely rare schwannomas originating in the fourth ventricle, without attachment to the surrounding structures. The clinical course, radiologic and pathological features, treatment, and follow-up are described. CASE DESCRIPTION: Case 1 was a 49-year-old man who presented with symptoms of paroxysmal dizziness and vomiting. Magnetic resonance imaging (MRI) showed a mixed solid-cystic mass occupying the inferior half of the fourth ventricle. Complete excision of the tumor was performed via midline suboccipital craniectomy. The histological diagnosis was intraventricular schwannoma. Case 2 was an 18-year-old man with chronic vertigo and progressive gait unsteadiness. MRI revealed a heterogeneously enhancing lesion completely filling the fourth ventricle. An Ommaya tube was placed in the ventricle to relieve symptoms of hydrocephalus, followed by tumor resection performed via a suboccipital craniotomy. Histopathological examination confirmed the diagnosis of schwannoma. CONCLUSIONS: Fourth ventricular schwannomas are rare but should be considered in the differential diagnosis of contrast-enhancing intraventricular tumors in both children and adults. Although their etiopathological origin may differ from that of extra-axial schwannomas, their imaging, histology, and clinical course appear to be identical, and these tumors should be managed similarly.

Sustained delivery of glial cell-derived neurotrophic factors in collagen conduits for facial nerve regeneration.

Facial nerve injury caused by traffic accidents or operations may reduce the quality of life in patients, and recovery following the injury presents unique clinical challenges. Glial cell-derived neurotrophic factor (GDNF) is important in nerve regeneration; however, soluble GDNF rapidly diffuses into body fluids, making it difficult to achieve therapeutic efficacy. In this work, we developed a rat tail derived collagen conduit to connect nerve defects in a simple and safe manner. GDNF was immobilized in the collagen conduits via chemical conjugation to enable controlled release of GDNF. The GDNF delivery system prevented rapid diffusion from the site without impacting bioactivity of GDNF; degradation of the collagen conduit was inhibited owing to the chemical conjugation. The artificial nerve conduit was then used to examine facial nerve regeneration across a facial nerve defect. Following transplantation, the artificial nerve conduits degraded gradually without causing dislocations and serious inflammation, with good integration into the host tissue. Functional and histological tests indicated that the artificial nerve conduits were able to guide the axons to grow through the defect, reaching the distal stumps. The degree of nerve regeneration in the group that was treated with the artificial nerve conduit approached that of the autograft group, and exceeded that of the other conduit grafted groups. STATEMENT OF SIGNIFICANCE: In this study, we developed artificial nerve conduits consisting of GDNF immobilized on collagen, with the aim of providing an environment for nerve regeneration. Our results show that the artificial nerve conduits guided the regeneration of axons to the distal nerve segment. GDNF was immobilized stably in the artificial nerve conduits, and therefore retained a sufficient concentration at the target site to effectively promote the regeneration process. The artificial nerve conduits exhibited good biocompatibility and facilitated nerve regeneration and functional recovery with an efficacy that was close to that of an autograft, and better than that of the other conduit grafted groups. Our approach provides an effective delivery system that overcomes the rapid diffusion of GDNF in body fluids, promoting peripheral nerve regeneration. The artificial nerve conduit therefore qualifies as a putative candidate material for the fabrication of peripheral nerve reconstruction devices.

Stem Cell Tracking Technologies for Neurological Regenerative Medicine Purposes.

The growing field of stem cell therapy is moving toward clinical trials in a variety of applications, particularly for neurological diseases. However, this translation of cell therapies into humans has prompted a need to create innovative and breakthrough methods for stem cell tracing, to explore the migration routes and its reciprocity with microenvironment targets in the body, to monitor and track the outcome after stem cell transplantation therapy, and to track the distribution and cell viability of transplanted cells noninvasively and longitudinally. Recently, a larger number of cell tracking methods in vivo were developed and applied in animals and humans, including magnetic resonance imaging, nuclear medicine imaging, and optical imaging. This review has been intended to summarize the current use of those imaging tools in tracking stem cells, detailing their main features and drawbacks, including image resolution, tissue penetrating depth, and biosafety aspects. Finally, we address that multimodality imaging method will be a more potential tracking tool in the future clinical application.

Evaluation of the Bone-ligament and tendon insertions based on Raman spectrum and its PCA and CLS analysis.

Injuries to the Anterior Cruciate Ligament (ACL) and Rotator Cuff Tendon (RCT) are common in physically active and elderly individuals. The development of an artificial prosthesis for reconstruction/repair of ACL and RCT injuries is of increasing interest due to the need for viable tissue and reduced surgically-related co-morbidity. An optimal prosthesis design is still elusive, therefore an improved understanding of the bone-soft tissue interface is extremely urgent. In this work, Raman spectral mapping was used to analyze, at the micron level, the chemical composition and corresponding structure of the bone-soft tissue interface. Raman spectroscopic mapping was performed using a Raman spectrometer with a 785 nm laser coupled to a microscope. Line-mapping procedure was performed on the ACL and RCT bone insertion sites. The classical least squares (CLS) fitting model was created from reference spectra derived from pure bone and soft-tissue components, and spectral maps collected at multiple sites from ACL and RCT specimens. The results suggest that different source of interface shows different boundary, even they seems have the same components. Compared to the common histology results, it provided intact molecular information that can easily distinguished some relative component change.