Xu-Ying He

Human umbilical vein-derived dopaminergic-like cell transplantation with nerve growth factor ameliorates motor dysfunction in a rat model of Parkinson's disease.

Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson’s disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.

Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells

BACKGROUND AIMS This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-β (TGF-β), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). METHODS Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-β, PDGF-BB, BDNF, GDNF and NGF. RESULTS The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. CONCLUSIONS The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.

Effect of Endovascular Treatment on Headache in Elderly Patients with Unruptured Intracranial Aneurysms

This study sought to determine if treating unruptured aneurysms in elderly patients has an effect on headaches, a common presenting symptom. Fifty-two of 72 subjects presented with headaches. Nearly 77% reported some improvement of their symptoms following endovascular treatment. The authors concluded that endovascular coiling of unruptured intracranial aneurysms resulted in relief of headache in most of these elderly patients. BACKGROUND AND PURPOSE: The incidence of unruptured intracranial aneurysms is increasing in the elderly population as life expectancy increases, and patients often present with headache. The goal of this study was to determine the effect of endovascular treatment on headache and identify factors associated with headache outcome in elderly patients with unruptured intracranial aneurysms. MATERIALS AND METHODS: A retrospective study was conducted for elderly patients (≥ 65 years old) being treated for unruptured intracranial aneurysms. Headache assessment was performed by a quantitative 11-point headache scale in all patients before and after endovascular treatment. Factors associated with headache outcome were investigated by univariate analyses. RESULTS: A total of 72 patients (mean age, 70.0 years; age range, 65–80 years; 41 women) fulfilled the inclusion criteria. There were 52 patients (72.2%) who presented with preoperative headache (headache score ≥ 1). Among them, 40 (76.9%) reported that headache score had an improvement according to their self-reported quantitative headache score after endovascular treatment. The average headache score was 5.63 preoperatively vs 2.50 postoperatively (P = .000). Twenty patients (27.8%) had no headache before treatment (headache score = 0), of whom 2 (10.0%) reported new onset of headache postoperatively. Only a preoperative headache score was associated with treatment outcome of headache, and a higher headache score predicted a lack of headache relief after endovascular treatment (P = .003). CONCLUSIONS: Endovascular coiling of unruptured intracranial aneurysms resulted in relief of headache in most of the elderly patients. Preoperative headache score was the only statistically significant predictor of headache outcome.

Nefiracetam Attenuates Pro-Inflammatory Cytokines and GABA Transporter in Specific Brain Regions of Rats with Post-Ischemic Seizures.

Background/Aims: Prior studies demonstrated that pro-inflammatory cytokines (PICs) including IL-1β, IL-6 and TNF-α contribute to regulation of epilepsy-associated pathophysiological processes in the specific brain regions, namely the parietal cortex, hippocampus and amygdala. Moreover, GABA transporter type 1 and 3 (GAT-1 and GAT-3) modulating extracellular GABA levels are engaged in the role played by PICs in epileptogenesis. Note that brain ischemic injury also elevates cerebral PICs. Thus, in this report we examined the effects of nefiracetam (NEF), a pyrrolidone derivative, on the levels of IL-1β, IL-6 and TNF-α, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala using a rat model of post-ischemic nonconvulsive seizure (NCS). Methods: NCS was evoked by the middle cerebral artery occlusion (MCAO). ELISA and Western Blot analysis were employed to determine the levels of PICs and GAT-1/GAT-3, respectively. Results: MCAO significantly increased IL-1β, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala as compared with sham control animals (P<0.05 vs. control rats). Also, in these specific brain regions expression of GAT-1 and GAT-3 was amplified; and the levels of GABA were decreased in rats following MCAO (P<0.05 vs. control rats). Systemic administration of NEF significantly attenuated the elevated PICs, amplified GAT-1 and GAT-3 as well as impaired GABA. NEF also attenuated the number of NCS events following MCAO. Conclusion: our data demonstrate that NEF improves post-ischemia evoked-NCS by altering PICs, GABA transporters thereby alleviating GABA in the parietal cortex, hippocampus and amygdala. This support a role for PICs and GABA in engagement of the adaptive responses associated with epileptic activity, but also suggests that NEF has anti-epileptic effects via PICs-GABA mechanisms, having pharmacological implications to target the specific PICs for neuronal dysfunction and vulnerability related to post-ischemic seizures and cognitive impairment.

Predictors of Favorable Outcome of Intracranial Basilar Dissecting Aneurysm

BACKGROUND Management of intracranial basilar dissecting aneurysms has been controversial and challenging, and surgical and conservative treatments usually have a bad prognosis. Our study aimed at evaluating the outcomes of endovascular treatment for these lesions and exploring the predictors of favorable outcome. METHODS We retrospectively reviewed 50 consecutive patients with basilar dissecting aneurysms from January 2006 to January 2013. Twenty-four patients underwent stent-assisted coiling whereas 26 patients underwent conservative treatment. Follow-up outcomes were evaluated using modified Rankin Scale (mRS) score. RESULTS Of the patients treated with stent-assisted coiling, 20 patients had a favorable outcome (mRS score, 0-1), post-treatment recurrence occurred in 3 patients, 1 had rebleeding, and 2 had no rebleeding. Of the patients treated with conservative therapy (observation or anticoagulation), 10 patients had an unfavorable outcome, 2 patients with ruptured aneurysms developed rebleeding, and 8 patients had poor outcome because of infarct progression. Stent-assisted coiling group had a more favorable outcome than the conservatively treated group (83.3% versus 55.2%, P = .019). Initial complete obliteration was related to the favorable outcome in endovascular-treated group (P = .042). Stent placement was the only independent predictor of favorable outcome in the logistic regression analysis (P = .030; odds ratio = 5.828; 95% confidence interval, 1.192-28.503). CONCLUSIONS Patients with basilar artery dissecting aneurysms treated with stent-assisted coiling had a more favorable outcome than the conservatively treated patients. Stent placement and initial complete occlusion were the favorable factors in patients with basilar dissecting aneurysm.

Single-centre comparison of procedural complications, clinical outcome, and angiographic follow-up between coiling and stent-assisted coiling for posterior communicating artery aneurysms

Aneurysm recurrence is a principle limitation of endovascular coiling procedures, especially in posterior communicating artery aneurysms, with reported recurrence rates of >30%. The adjunctive use of self-expandable stents has revolutionised the treatment of intracranial aneurysms, especially for complex morphologies, wide necks, or unfavourable dome-to-neck ratios. However, there are limited data concerning a direct comparison between simple coiling and stent-assisted coiling in posterior communicating artery aneurysms. This study aimed to compare the durability and outcomes of coiling versus stent-assisted coiling procedures. Imaging data of patients with posterior communicating artery aneurysms treated with coiling or stent-assisted coiling between January 2008 and October 2012 were retrospectively analysed. The initial angiographic results, procedural complications, and clinical outcomes were assessed at discharge. Imaging follow-up was performed with cerebral angiography. Complete aneurysm occlusion was achieved on initial angiography in 23/56 (41.1%) stent and 83/235 (35.3%) non-stent patients. At the latest follow-up (mean follow-up 14.3 ± 10.4 months for stent and 13.2 ± 9.5 months for non-stent patients), aneurysms had recurred in 5/47 (10.6%) stent and 57/203 (28.1%) non-stent patients (p=0.014). Procedural complications occurred in 6/56 (10.7%) stent and 27/235 (11.5%) non-stent aneurysms. No rebleeding occurred during clinical follow-up (mean duration, 46.7 months). Recurrence rates at the latest follow-up were significantly lower in patients undergoing stent-assisted coiling than those undergoing simple coiling. Thus, use of the stent-assisted neck remodelling technique in the treatment of wide-necked posterior communicating artery intracranial aneurysms appears to improve the long-term clinical outcome.

Treatment of giant/large internal carotid aneurysms: parent artery occlusion or stent-assisted coiling

Purpose: Treatment of giant/large internal carotid aneurysm is a challenge for neurologists. Previously, parent artery occlusion was the classic therapy; now the stent-assisted coil embolization has become available in recent years, but the optimal therapy is under debate. The goal of the present study was to compare two endovascular treatment modalities in terms of safety, efficacy and short-term outcomes. Methods: All the patients were divided into two groups: Group A: patients who underwent parent artery occlusion, and Group B: patients who underwent stent-assisted coil embolization. Follow-up outcomes were evaluated using the modified Rankin Scale (mRS). Results: After 12 months of follow-up, the favorable outcome (mRS: 0–2) had no statistical significance in both groups (p = 1.00). Patients in group A had greater ischemia compared with patients in group B, but the difference did not reach statistical significance (p = 0.421). In group B, patients had a higher rate of partial occlusion (p = 0.255) and recurrence (10% vs. 0%; p = 0.586). Conclusions: Stent-assisted coiling may not be superior to parent artery occlusion in selected patients after short-term follow-up. Parent artery occlusion is a simple, safe and effective treatment for large/giant internal carotid aneurysms.

Comparative efficacy of Glubran and polyvinyl-alcohol particles in the embolization of meningiomas

Purpose: Preoperative embolization of meningiomas decreases intraoperative bleeding and shortens operation time. However, in meningiomas predominantly vascularized by the internal carotid artery (ICA) or vertebral artery (VA) branches, embolization of external carotid artery feeder branches may lead to a hemodynamic increase in blood supply from the ICA or VA, whereas embolization of ICA or VA feeder branches with particle embolic agents may be associated with complications. This study investigated the safety and efficacy of Glubran, a liquid embolic agent, for the embolization of this type of meningioma compared with polyvinyl-alcohol (PVA) particles. Materials and methods: From January 2006 to June 2015, 157 consecutive patients (98 females; mean age = 48.3 years) who suffered from meningiomas and were preoperatively referred for embolization were retrospectively analyzed. Glubran (n = 40) and PVA (n = 55) were used to devascularize tumors. Sixty-two patients were not embolized because of dangerous anastomosis or other tumor characteristics. Intraoperative blood loss, intraoperative time, degree of angiographic devascularization and embolization-related complications were analyzed. Results: The intraoperative blood loss and operative time were significantly lower in the Glubran-embolized versus non-embolized group. Furthermore, Glubran embolization significantly reduced intraoperative blood loss and operative time for meningiomas that received their primary blood supply from the ICA and/or VA compared with PVA embolization. Conclusions: Preoperative meningioma embolization with Glubran decreases intraoperative blood loss and operative time. Furthermore, embolization with Glubran produces more effective devascularization compared with PVA for meningiomas supplied by the ICA and/or VA. Thus, Glubran may represent a better embolic agent for this meningioma subtype.

Treatment of unruptured vertebral dissecting aneurysms: internal trapping or stent-assisted coiling

Purpose: Endovascular treatment is an attractive approach for the treatment of unruptured vertebral dissecting aneurysms, and includes internal trapping and stent-assisted coil embolization. However, the optimal therapy remains debatable. We reviewed our experience with both endovascular treatment modalities and compared the safety, efficacy, and short-term outcomes for each approach. Materials and Methods: We retrospectively reviewed 65 consecutive patients with unruptured vertebral dissecting aneurysms who underwent endovascular treatment between January 2003 and January 2014. 24 patients underwent endovascular internal trapping (group A) while 41 patients underwent stent-assisted coiling (group B). Thirteen patients underwent single stent with coiling while 28 patients underwent double or three stent-assisted coiling. Short-term outcomes were evaluated using the modified Rankin Scale. Results: A favorable clinical outcome was achieved in 58 of 65 patients. Procedure-related complications included ischemic symptoms (n = 6) and recurrence (n = 4). There was no statistical difference in modified Rankin Scale scoring between groups. Group A patients had more ischemia symptoms compared with group B patients (p = 0.043), Group B patients had higher recurrence rates compared with group A patients, but the difference had no statistical significance (p = 1.00). However, recurrence only occurred in patients who underwent stent-assisted coiling alone (p = 0.046). Conclusion: Stent-assisted coiling for unruptured vertebral dissecting aneurysms may maintain artery patency. Multilayer disposition of stents with coils may decrease complications and facilitate aneurysm occlusion. Larger, prospective studies are necessary to determine the long-term outcomes of reconstructive therapy.

Photothrombosis combined with thrombin injection establishes a rat model of cerebral venous sinus thrombosis

OBJECTIVE Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening disease and an animal model for in-depth study of CVST is needed. This study aimed to develop a rat model suitable for studying clinically relevant aspects of CVST and investigating its dynamic pathophysiological changes during a 7-day period. METHOD A photothrombosis method was used to create a rat sinus-vein thrombosis model. A spot size-adjustable Diode Pumped Solid State laser (DPSS) combined with thrombin injection occluded the rostral and caudal superior sagittal sinus (SSS). The model was used to evaluate pathophysiological changes at different time points over 7 days. Evans Blue dye injection was used to detect alterations in blood-brain barrier (BBB) permeability. Brain water content was also measured. Moreover, we examined changes in brain infarct volume, neurological function, as well as histology after induction of CVST. RESULT CVST in rats significantly altered BBB permeability, consistent with the development of brain edema. It was accompanied by an increase in brain infarct volume and deficits in neurological function that began on day 1, peaked on day 2, and typically improved by day 7 due to the neuroprotective effects of angiogenesis and gliocyte proliferation. CONCLUSION In this study, we describe a rat model that produces clinically relevant pathophysiology and pathology that will facilitate evaluation of therapeutic regimens for CVST. Furthermore, our results indicate a period of optimal clinical intervention for patients with CVST, which may reduce the probability of dependency and death.