Summary
Significant progress has been made during the past few decades in stem cell therapy research for various diseases and injury states; however this has not been overwhelmingly translated into approved therapies, despite much public attention and the rise in unregulated ‘regenerative clinics’. In the last decade, preclinical research focusing on mesenchymal stem/stromal cell (MSC) therapy in experimental animal models of hemorrhagic stroke has gained momentum and has led to the development of a small number of human trials. Here we review the current studies focusing on MSC therapy for hemorrhagic stroke in an effort to summarize the status of preclinical and clinical research. Preliminary evidence indicates that MSCs are both safe and tolerable in patients, however future randomized controlled trials are required to translate the promising preclinical research into an effective therapy for hopeful patients.
Degeneration of basal forebrain cholinergic neurons (BFCNs) precedes hippocampal degeneration and pathological amyloid-beta (Aβ) accumulation, and underpins the development of cognitive dysfunction in sporadic Alzheimer’s disease (AD). We hypothesized that degeneration of BFCNs causes a decrease in neurotrophin levels in innervated brain areas, which in turn promotes the development of Aβ pathology and cognitive impairment. Here we show that lesion of septo-hippocampal BFCNs in a pre-symptomatic transgenic amyloid AD mouse model (APP/PS1 mice) increases soluble Aβ levels in the hippocampus, and induces cognitive deficits in a spatial memory task that are not seen in either unlesioned APP/PS1 or non-transgenic littermate control mice. Furthermore, the BFCN lesion results in decreased levels of brain-derived neurotrophic factor (BDNF). However, viral knockdown of neuronal BDNF in the hippocampus of APP/PS1 mice (in the absence of BFCN loss) neither increased the level of Aβ nor caused cognitive deficits. These results suggest that the cognitive decline and Aβ pathology induced by BFCN loss occur independent of dysfunctional neuronal BDNF signaling, and may therefore be directly underpinned by reduced cholinergic neurotransmission.
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