Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPα levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPα (TgsAPPα mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPα mice, and those derived from wild-type mice treated with sAPPα, displayed suppressed β-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.
Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation; however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.
As guest editors of this special issue, we are delighted to present 13 articles that discuss advances in stroke research including translational stroke research, stroke research milestones, and proposals for future directions. Stroke is a major cause of disability, and, according to the Centers for Disease Control and Prevention, is the fifth leading cause of death in the US alone. Possible factors contributing to stroke pathogenesis are elucidated and possible treatment modalities are explored in the following special issue of Cell Transplantation.
We are pleased to announce the exciting news that SAGE Publishing, Inc. is now the new publisher of Cell Transplantation. As SAGE's medical publishing portfolio has continued to grow, they took notice of the potential of our journal and approached us regarding their vision for the continued development of this publication. We feel the advantages of working with SAGE are numerous, and we expect this change will result in expansion of the global reach and impact of the journal. Shinn-Zong (John) Lin and Paul R. Sanberg are pleased to have been asked to remain on as Co-Editors-in-Chief of Cell Transplantation, and we expect that there will be no delay in the publication schedule. The Editorial Board will remain essentially the same, including Samantha Portis as Managing Editor (previously Associate Editor). We're also pleased to welcome our new editorial assistant, Kuan-I (Josephine) Lin from Taiwan. Currently, all submission, editorial, and review processes will remain the same. SAGE will continue to work with the Manuscript Central site, and all published content will remain on IngentaConnect through the end of 2017. On behalf of all who have been involved with Cell Transplantation since its inception in 1992, we would like to acknowledge Cognizant Communication Corporation for recognizing the journal's potential over 26 years ago and for their devotion, development, hard work, and
Traumatic brain injury (TBI) is a debilitating injury that affects numerous individuals, as it may result from trauma sustained by motor vehicle accidents, sports injuries, combat, or other events. The long-term effects of TBI are debilitating and pervasive and can impact an individual's family, career, and overall ability to function in society. This special issue of Cell Transplantation is dedicated to providing new information related to biological therapies for TBI and factors contributing to disability, including discussions about inflammation, the elucidation of new molecular targets, alterations in gene expression, cell therapy, neurogenesis, and therapeutic molecules. This special issue underscores the need for more investigation of TBI and presents a wide array of research currently being conducted.Galgano et al. open the issue by providing background information and reviewing the current clinical treatment modalities for TBI, including surgical interventions and postinjury seizure prophylaxis. Mild TBI is discussed in a second review by Fehily et al., and the final review discusses how changes in dopamine levels may exacerbate the pathogenesis and pathophysiology of TBI.In a study of military personnel with TBI, Devoto et al. discuss the role of inflammation in long-term behavioral and neurological deficits resulting from the injury. The researchers found a relationship between chronic inflammation and brain dysfunction and a relationship between the comorbidity of TBI and post-traumatic stress disorder (PTSD) and inflammation.Other studies in the issue focused on beneficial molecules in TBI therapy. Merkel et al. found that dexamethasone may be a viable option for curbing TBI-associated cocaine dependence, as individuals with TBI are often susceptible to substance abuse. Withania somnifera, a root extract commonly used in traditional medicine, was evaluated as a potential neuroprotective agent for TBI by Saykally et al. Lastly, Allitt et al. found that progesterone helped improve the response profile (neuronal firing) in the cortex of a rat model of TBI.Transplantation studies using extracellular matrix (ECM) and cells are also included in the current issue. Wu et al. used ECM derived from porcine (pig) brains to transplant TBI-modeled mice and found that neurobehavioral function was improved and lesion volume was reduced. Focused ultrasound and magnetic targeting of human neural progenitor cells in rats was explored by Shen et al., who showed that migration of therapeutic cells to the brain was improved. Beretta et al. also transplanted therapeutic cells for a murine model of TBI. Using human neural stem cells (hNSCs), the researchers showed that performance on hippocampal-based memory tasks was improved. Likewise, Wang et al. transplanted a rat model of TBI with mouse-derived neural stem cells (NSCs), which resulted in decreased apoptosis and improved neurological function, as evidenced by neurological severity scores (NSS). The findings in these studies raise the question of whether various patholo...
There is currently a dearth of treatment options for stroke or traumatic brain injury that can restore cognitive and motor function. Regenerative and translational medicine have ushered forth promising new methods for mediating recovery in the central nervous system, the most salient of which are rehabilitation and stem cell therapies that, when combined, result in more pronounced recovery than one approach alone.
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