Huancong Zuo

Synergistic Effect of Neural Stem Cells and Olfactory Ensheathing Cells on Repair of Adult Rat Spinal Cord Injury

Spinal cord injury (SCI) is a common clinical disease that places a heavy burden on families and society. Cellular therapy provides a method of giving a supplement of cells lost in the injury and promoting functional recovery after SCI. Neural stem cells (NSCs) and olfactory ensheathing cells (OECs) are two most promising cell types. NSCs have the potential of differentiating into neurons and glial cells, and OECs could help the axons of neurons pass through the glial scar to promote functional recovery. NSCs were isolated from the cortices of fetal rats on days 12–14 of embryonic development and OECs were isolated from the olfactory bulbs of adult rats. In vitro coculture studies demonstrated OECs could promote NSCs to differentiate into neurons. Four groups of rats that had been 3/4 spinal cord transectioned at T9 were injected with DMEM/F12 solution, NSCs, OECs, and NSCs + OECs, respectively, 7 days post-SCI. Twelve weeks postoperation, the hindlimb locomotor function of rats in the cotransplantation group was significantly improved compared with that in the other three groups. Histological observation and immunohistochemical staining of NF-200 both showed new nerve fibers across the injured region. Cotransplantation of NSCs and OECs might have a synergistic effect on promoting neural regeneration and improving the recovery of locomotion function. Cotransplantation of NSCs and OECs was better than a single graft of either NSCs or OECs. These findings have provided a new way of thinking in the treatment of SCI.

Phosphorylation of tau protein over time in rats subjected to transient brain ischemia

Transient brain ischemia has been shown to induce hyperphosphorylation of the microtubule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction between tau, glycogen synthase kinase (GSK)-3β and protein phos-phatase 2A. The results confirmed that tau protein was dephosphorylated during brain ischemia; in addition, the activity of GSK-3β was increased and the activity of protein phosphatase 2A was decreased. After reperfusion, tau protein was hyperphosphorylated, the activity of GSK-3β was decreased and the activity of protein phosphatase 2A remained low. Importantly, the interaction of tau with GSK-3β and protein phosphatase 2A was altered during ischemia and reperfusion. Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3β and protein phosphatase 2A, and improve learning and memory ability of rats after transient brain ischemia. The present study demonstrated that it was the interaction of tau with GSK-3β and protein phosphatase 2A, rather than their individual activities, that dominates the phosphorylation of tau in transient brain ischemia. Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke. The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.

Decreased expression of microRNA-107 predicts poorer prognosis in glioma.

The expression level of microRNA-107 (miR-107) has been proved to be decreased in many human malignant cancers. Especially in glioma, accumulating evidence indicates that miR-107 may play important parts in cell proliferation, apoptosis, and invasion in glioma. However, its clinical significance in glioma has not been investigated. This study aims at investigating the relationship between miR-107 expression level and clinical significance and analyzing its value of miR-107 in valuing the prognosis of glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of miR-107 in 80 glioma and 17 normal brain tissues. The results showed the miR-107 expression level in glioma tissues was significantly lower than those in normal brain tissues (p < 0.001). The decreased expression of miR-107 in glioma was positively associated with high WHO grade (p < 0.001), low Karnofsky performance score (KPS) (p < 0.001), and large tumor size (p < 0.001) and had a significant impact on overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) according to Kaplan–Meier survival with log-rank test. Finally, Cox regression analyses showed that low miR-107 expression (p < 0.001) might be an independent prognostic parameter to predict poor prognosis. In conclusion, it is the first data to prove that expression level of miR-107 may be a novel and valuable prognostic factor in glioma.

Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury

Amyloid β-peptide, a major component of senile plaques in Alzheimers disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimers disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid β-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid β-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3β were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid β-peptide administration than those under-going cerebral ischemia-reperfusion or amyloid β-peptide administration alone. Conversely, the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid β-peptide administration. These findings suggest that amyloid β-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.

Cell transplantation as a pain therapy targets both analgesia and neural repair.

Cell transplantation is a potentially powerful approach for the alleviation of chronic pain. The strategy of cell transplantation for the treatment of pain is focused on cell-based analgesia and neural repair. (1) Adrenal medullary chromaffin cells and the PC12 cell line have been used to treat cancer pain and neuropathic pain in both animal models and human cases. As biological or living minipumps, these cells produce and secrete pain-reducing neuroactive substances if administered directly into the spinal subarachnoid space. (2) Cell implantation for pain neurorestorative therapy is a new concept and an emerging research field for pain control along with neural repair. Possible neurorestorative mechanisms include neuroprotective, neurotrophic, neuroreparative, neuroregenerative, neuromodulation, or neuroconstructive interventions, as well as immunomodulation and enhancing the microcirculation. These factors may ultimately restore the damaged or irritated condition of the lesioned nerves. The growing preclinical and clinical data show that neural stem/progenitor cells, olfactory ensheathing cells, mesenchymal stromal cells, and CD34+ cells have the capacity to manage intractable pain and improve neurological functions. Cell delivery routes include local, intrathecal, or intravascular implants. Although these strategies are still in their infancy phase for pain neurorestoratology, cell-based therapies could open up new avenues for the relief of pain. In this review, these aspects are critically analyzed based on our own investigations. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Axial MR diffusion tensor imaging and tractography in clinical diagnosed and pathology confirmed cervical spinal cord astrocytoma

OBJECTIVE To evaluate the diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) features of cervical spinal cord astrocytoma. METHODS Eleven patients with cervical spinal cord astrocytomas and 10 healthy volunteers were recruited in this study. Conventional magnetic resonance imaging (MRI) and axial DTI were performed on a 3.0T MRI system. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values for the lesions were measured. DTT was performed using the principal diffusion direction method. RESULTS ADC values of the lesions and the normal-appearing tissue around the tumour (NATAT) on T2-weighted imaging (T2WI) increased. The ADC values of the lesions were higher. The FA values of the lesions and the NATAT decreased significantly, with the lesions having lower FA values. The RD value (1.36±0.49) of the tumours was significantly higher than those found in the healthy controls, but similar for the AD value (1.84±0.56). There were no differences in ADC or FA values between lesions and NATAT in McCormick Type I vs. Type II patients. Based on the DTT, 7 patients with solid mass tumours were classified as Type I. One patient with a solid mass, 2 patients with cystic degeneration inside the lesions, and 1 patient with a cyst around the mass were classified as Type II. CONCLUSIONS FA values of the cervical spinal cord astrocytoma decreased, but the ADC values increased. DTI was sensitive for the evaluation of pathological changes that could not be visualized on T2WI. Our preliminary study indicates that DTT can be used to guide operation planning, and that axial images of DTT may be more valuable.

Repairing skull defects in children with nano-hap/collagen composites: A clinical report of thirteen cases

ObjectiveTo evaluate the clinical results of repairing skull defects with biomimetic bone (nano-hap/collagen composites, NHACs) in children.MethodsThirteen children with skull defects were treated ...

Controlled release of nerve growth factor and basic fibroblast growth factor combined with small-gap anastomosis enhances sciatic nerve regeneration

ObjectivesNerve regeneration after peripheral nerve injury is a slow process with a limited degree of functional recovery, resulting in a high disability rate. Thus, accelerating the rate of nerve regeneration and improving the degree of nerve repair is a clinical challenge. This study aimed to investigate the role of growth factor gel combined with small-gap nerve anastomosis in the regeneration of sciatic nerve injury in rats. This was achieved by injecting nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) gel into a silicon chamber that bridged the transection of the nerve.MethodsIn 27 randomly chosen Sprague Dawley rats, a sharp blade was used to transect the right hind leg sciatic nerve. The rats were divided into 3 groups: in groups A and B, silicon tubes containing NGF and bFGF gel or saline, respectively, were used to bridge the nerve proximal and distal ends (3-mm gap), and in group C, the nerve proximal and distal ends were directly sutured. Eight weeks after surgery, the sciat...

Novel Method to Identify the Precentral Gyrus and Its Detailed Functional Distribution in Real Brain Surfaces Using Reconstructed 3D Brain Surface Imaging

Objective: To study the use of reconstructed 3D brain surface imaging (RBSI) to identify the precentral gyrus and its detailed functional distribution in epileptic patients. Method: A total of 12 refractory epilepsy cases that need intracranial electrode implantation were studied. In these patients, pre-operative magnetic resonance imaging (MRI) and functional MRI (fMRI) were conducted, and a cranial computed tomography (CT) scan was performed after electrode implantation. The RBSI was accomplished using Brain Voyager software based on MRI data, and then the 3D brain surface was integrated with the subdural electrode CT scan. The precentral gyrus was found in the reconstructed brain surface imaging according to their anatomical shape, and then were identified in the surgical field by comparing the exposed gyrus in the RBSI with the help of intraoperative photographs. Results: Total 12 cases of precentral gyrus was found and marked in the RBSI. There were 101 electrodes covering the precentral gyrus and 73 (72%) of them had motor response to electrical stimulation. In the contrast, (the area which is 1 cm ahead of the precentral gyrus), the motor response rate was 13% (17/130) (p < 0.05). During fMRI, 100% of the precentral gyrus and 58% (7/12) of post central gyrus was activated during hand movement. Whereas, no activation of the areas ahead of precentral gyrus was seen showing a significant difference between precentral gyrus and gyrus ahead. Conclusion: Our results demonstrated that using RBSI technique, it is possible to identify the precentral gyrus with precision.