Clinical Efficacy and Meta-Analysis of Stem Cell Therapies for Patients with Brain Ischemia

Objective. Systematic review and meta-analysis to observe the efficacy and safety of stem cell transplantation therapy in patients with brain ischemia. Methods. We searched Cochrane Library, PubMed, Ovid, CBM, CNKI, WanFang, and VIP Data from its inception to December 2015, to collect randomized controlled trials (RCT) of stem cell transplantation for the ischemic stroke. Two authors independently screened the literature according to the inclusion and exclusion criteria, extracted data, and assessed the risk of bias. Thereafter, meta-analysis was performed. Results. Sixteen studies and eighteen independent treatments were included in the current meta-analysis. The results based upon the pooled mean difference from baseline to follow-up points showed that the stem cell transplantation group was superior to the control group with statistical significance in the neurologic deficits score (NIHSS, MD = 1.57; 95% CI, 0.64-2.51; I2 = 57 %; p = 0.001), motor function (FMA, MD = 4.23; 95% CI, 3.08-5.38; I2 = 0 %; p <0.00001), daily life ability (Barthel, MD = 8.37; 95% CI, 4.83-11.91; I2 = 63 %; p <0.00001), and functional independence (FIM, MD = 8.89; 95% CI, 4.70-13.08; I2 = 79 %; p <0.0001). Conclusions. It is suggested that the stem cell transplantation therapy for patients with brain ischemic stroke can significantly improve the neurological deficits and daily life quality, with no serious adverse events. However, higher quality and larger data studies are required for further investigation to support clinical application of stem cell transplantation

The 2021 yearbook of neurorestoratology

Breakthroughs with rapid changes are the themes of the development in Neurorestoratology this year. Given the very difficult circumstances of the persistent COVID-19 pandemic, most of the colleagues in Neurorestoratology have conducted meaningful research and obtained encouraging results, as described in the 2020 Yearbook of Neurorestoratology. Neurorestorative progress during 2021 depicts recent findings on the pathogenesis of neurological diseases, neurorestorative mechanisms and clinical therapeutic achievements. The pathogenesis and risk factors of Alzheimer\u27s disease were parts of the most prominent hot research topics. Yet, it remains controversial whether β-amyloid accumulation and tau protein deposition are the results of, or the reasons for the neurodegenerative processes. Neurogenesis is an important neurorestorative mechanism, however, it is questionable whether neural stem cells are present in the adult humans brain. Thus, neurogenesis may not derive from endogenous neural stem cells in the adult humans. Neurorestorative treatments were important areas of the 2021 research efforts and these therapies are improving the quality of life in patients with neurological diseases. There was major exploration of cell-based therapies for neurological disease and injury. However, unfortunately several multi-center, double-blind or observing-blind, placebo controlled, randomized clinical trials of mesenchymal stromal cells or products of mesenchymal stem cells failed to show positive results in ischemic stroke when employed in the sub-acute or recovery phases as there were no appreciable differences in the quality of life as compared with controls. Excitingly, increased numbers of clinical investigations of brain–computer interface (BCI) were reported that showed benefits for patients with neurological deficits. In pharmaceutical neurorestorative therapies, Aducanumab (Aduhelm) and Sodium Oligomannate are approved respectively by the United States Food and Drug Administration (USFDA) and the China National Medical Products Administration (NMPA) to treat patients with mild-to-moderate Alzheimer\u27s disease. Although, the decisions to approve these drugs are highly contentious in the medical and scientific community because of the contradictory findings or other problems associated with the drug usage. We believe that repeating low-level evidence studies that showed negative results or scanty evidences in randomized control trials is of little significance. However, we strongly recommend conducting multi-center, double-blind, placebo controlled, randomized clinical trials for promising innovative therapeutic methods to facilitate their possible clinical translation

Engineered Extracellular Vesicles for Drug Delivery in Therapy of Stroke

Extracellular vesicles (EVs) are promising therapeutic modalities for treating neurological conditions. EVs facilitate intercellular communication among brain cells under normal and abnormal physiological conditions. The potential capability of EVs to pass through the blood–brain barrier (BBB) makes them highly promising as nanocarrier contenders for managing stroke. EVs possess several potential advantages compared to existing drug-delivery vehicles. These advantages include their capacity to surpass natural barriers, target specific cells, and stability within the circulatory system. This review explores the trafficking and cellular uptake of EVs and evaluates recent findings in the field of EVs research. Additionally, an overview is provided of the techniques researchers utilize to bioengineer EVs for stroke therapy, new results on EV–BBB interactions, and the limitations and prospects of clinically using EVs for brain therapies. The primary objective of this study is to provide a comprehensive analysis of the advantages and challenges related to engineered EVs drug delivery, specifically focusing on their application in the treatment of stroke

An endovascular approach to ruptured aneurysms of the circumferential branch of the basilar artery

Aneurysms of the basilar perforating arteries are uncommon and those of the circumferential artery are particularly rare. Microsurgical clipping or trapping is the preferred treatment as these aneurysms are usually not accessible for endovascular treatment. We report two patients with ruptured aneurysms arising from the basilar circumferential artery. The first patient, a 66-year-old male, presented with a prepontine hematoma and a delayed filling aneurysm of the basilar circumferential artery. The second patient, a 28-year-old female, presented with a narrow-neck aneurysm of the basilar circumferential artery, associated with an arteriovenous malformation in the left cerebellum. Both patients were treated successfully with endovascular coiling, flow was preserved in the perforating parent vessels and the patients had excellent outcomes. This is the first report of this type of aneurysm being successfully treated by endovascular coiling. The treatment challenges regarding microsurgical and endovascular approaches are discussed. (C) 2011 Elsevier Ltd. All rights reserved

A Prospective Study of Nonfunctioning Pituitary Adenomas: Presentation Management and Clinical Outcome

A prospective study was performed to evaluate the presentation, therapeutic management, and clinical outcome of nonfunctioning pituitary adenomas (NFPAs). In most of 385 consecutive patients, NFPAs were macroadenomas. The mean follow-up duration was 5.5 ± 1.4 years. Presentation was dominated by headache, visual disturbance, and hypopituitarism. Pituitary apoplexy (clinical and subclinical) was observed in 88 patients. Appropriate steroids replacement was given before surgery. Endoscope-assisted transsphenoidal surgery (TSS) was performed, and was well tolerated by all patients. At discharge, visual disturbances were improved in 215 (87.6%) patients who had complained of visual impairment preoperatively. The shorter the time from presentation of pituitary apoplexy to surgery, the better the outcome in visual function. Seventy-two (18.7%) patients developed transient diabetes insipidus (DI) and 85 (22.1%) patients developed hyponatremia, but all these improved within six weeks. Hypocortisolism was confirmed in 84 (21.8%) patients with an abnormal postoperative day 2 (POD2) 0800 serum cortisol level and in 122 (31.7%) patients with an abnormal POD6 0800 serum cortisol level. Hypothyroidism occurred in 135 (35.1%) patients. Steroids replacement was thus given immediately. Eight (2.1%) patients needed lifetime hormone substitution. No adrenal crisis occurred. Five (1.3%) patients died within six weeks. Residual tumors were confirmed in 79 patients (20.8%) by postoperative four-month enhanced MR imaging. Tumor recurrence or regrowth occurred in 56 patients (14.7%) during the follow-up period. These patients required repeat TSS or radiosurgery. The findings of this study support the use of TSS as a feasible initial treatment for NFPAs. With appropriate perioperative management of abnormal fluid, electrolyte, and endocrinological function, TSS was associated with minimum morbidity and was well tolerated by patients regardless of age. However, close screening of pituitary function and adequate neuroradiological follow-up should be performed after surgery for detection of tumor recurrence or regrowth. The indications for repeat TSS and postoperative radiosurgery in residual or recurrent NFPAs should be better defined. © 2010 Springer Science+Business Media, LLC

Expressions of Fas/DcR3 and RGD-FasL mediated apoptosis in pituitary adenomas

Purpose: To detect the expressions of Fas/DcR3 and to investigate the cytotoxic effects of RGD-FasL on pituitary adenoma cells. Materials and Methods: Fas/DcR3 mRNAs were detected by Reverse transcription polymerase chain reaction (RT-PCR) and their surface expressions were measured by flow cytometry. Cytotoxicities exerted by FasL and newly-constructed RGD-FasL on tumor cells were measured with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic cells were examined by electron microscopy and the induced apoptosis was determined by agarose gel electrophoresis. The cell cycle was assessed by flow cytometry with ANNEXIN V FITC/PI. The expressions of caspases, Bcl-2, RANKL and JNK2 were detected by Western blotting. Results: Fas/DcR3 was expressed in GH3/MMQ/AtT20 cells. The cytotoxic effects of RGD-FasL on tumor cells were seen in a dose-dependent manner. These cells showed the same sensitivity to RGD-FasL as to FasL. RGD-FasL induced apoptosis and G1/G0 arrest. The expressions of caspase-8/9/3, RANKL, JNK2 were increased while that of Bcl-2 was decreased with treatment of RGD-FasL. Conclusions: Fas can be a novel target for the treatment of pituitary adenomas. RGD-FasL induces apoptosis of pituitary adenoma cells through caspase activation

A prospective study of nonfunctioning pituitary adenomas: presentation, management, and clinical outcome

State Administration of Foreign Experts Affairs of ChinaA prospective study was performed to evaluate the presentation, therapeutic management, and clinical outcome of nonfunctioning pituitary adenomas (NFPAs). In most of 385 consecutive patients, NFPAs were macroadenomas. The mean follow-up duration was 5.5 +/- A 1.4 years. Presentation was dominated by headache, visual disturbance, and hypopituitarism. Pituitary apoplexy (clinical and subclinical) was observed in 88 patients. Appropriate steroids replacement was given before surgery. Endoscope-assisted transsphenoidal surgery (TSS) was performed, and was well tolerated by all patients. At discharge, visual disturbances were improved in 215 (87.6%) patients who had complained of visual impairment preoperatively. The shorter the time from presentation of pituitary apoplexy to surgery, the better the outcome in visual function. Seventy-two (18.7%) patients developed transient diabetes insipidus (DI) and 85 (22.1%) patients developed hyponatremia, but all these improved within six weeks. Hypocortisolism was confirmed in 84 (21.8%) patients with an abnormal postoperative day 2 (POD2) 0800 serum cortisol level and in 122 (31.7%) patients with an abnormal POD6 0800 serum cortisol level. Hypothyroidism occurred in 135 (35.1%) patients. Steroids replacement was thus given immediately. Eight (2.1%) patients needed lifetime hormone substitution. No adrenal crisis occurred. Five (1.3%) patients died within six weeks. Residual tumors were confirmed in 79 patients (20.8%) by postoperative four-month enhanced MR imaging. Tumor recurrence or regrowth occurred in 56 patients (14.7%) during the follow-up period. These patients required repeat TSS or radiosurgery. The findings of this study support the use of TSS as a feasible initial treatment for NFPAs. With appropriate perioperative management of abnormal fluid, electrolyte, and endocrinological function, TSS was associated with minimum morbidity and was well tolerated by patients regardless of age. However, close screening of pituitary function and adequate neuroradiological follow-up should be performed after surgery for detection of tumor recurrence or regrowth. The indications for repeat TSS and postoperative radiosurgery in residual or recurrent NFPAs should be better defined