Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease.

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals. The comorbidity of the two neurological disorders represents a grave health threat to older populations. This review presents a brief background of the development of novel concepts and their clinical potentials.

Reprogramming Glioblastoma Cells into Non-Cancerous Neuronal Cells as a Novel Anti-Cancer Strategy.

Glioblastoma Multiforme (GBM) is an aggressive brain tumor with a high mortality rate. Direct reprogramming of glial cells to different cell lineages, such as induced neural stem cells (iNSCs) and induced neurons (iNeurons), provides genetic tools to manipulate a cell's fate as a potential therapy for neurological diseases. NeuroD1 (ND1) is a master transcriptional factor for neurogenesis and it promotes neuronal differentiation.

Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: implications for preventive treatments of ischemic stroke and late-onset Alzheimer's disease.

Stroke and late-onset Alzheimer's disease (AD) are risk factors for each other; the comorbidity of these brain disorders in aging individuals represents a significant challenge in basic research and clinical practice. The similarities and differences between stroke and AD in terms of pathogenesis and pathophysiology, however, have rarely been comparably reviewed. Here, we discuss the research background and recent progresses that are important and informative for the comorbidity of stroke and late-onset AD and related dementia (ADRD).

Glycosaminoglycan scaffolding and neural progenitor cell transplantation promotes regenerative immunomodulation in the mouse ischemic brain.

Ischemic stroke is a leading cause of morbidity and mortality, with limited treatments that can facilitate brain regeneration. Neural progenitor cells (NPCs) hold promise for replacing tissue lost to stroke, and biomaterial approaches may improve their efficacy to overcome hurdles in clinical translation. The immune response and its role in stroke pathogenesis and regeneration may interplay with critical mechanisms of stem cell and biomaterial therapies.

Pathogenesis of sporadic Alzheimer's disease by deficiency of NMDA receptor subunit GluN3A.

The Ca hypothesis for Alzheimer's disease (AD) conceives Ca dyshomeostasis as a common mechanism of AD; the cause of Ca dysregulation, however, is obscure. Meanwhile, hyperactivities of N-Methyl-D-aspartate receptors (NMDARs), the primary mediator of Ca influx, are reported in AD. GluN3A (NR3A) is an NMDAR inhibitory subunit.

Conversion of Reactive Astrocytes to Induced Neurons Enhances Neuronal Repair and Functional Recovery After Ischemic Stroke.

The master neuronal transcription factor NeuroD1 can directly reprogram astrocytes into induced neurons (iNeurons) after stroke. Using viral vectors to drive ectopic ND1 expression in gliotic astrocytes after brain injury presents an autologous form of cell therapy for neurodegenerative disease. Cultured astrocytes transfected with ND1 exhibited reduced proliferation and adopted neuronal morphology within 2-3 weeks later, expressed neuronal/synaptic markers, and extended processes.

Cortical Transplantation of Brain-Mimetic Glycosaminoglycan Scaffolds and Neural Progenitor Cells Promotes Vascular Regeneration and Functional Recovery after Ischemic Stroke in Mice.

Stroke causes significant mortality and morbidity. Currently, there are no treatments which can regenerate brain tissue lost to infarction. Neural progenitor cells (NPCs) are at the forefront of preclinical studies for regenerative stroke therapies.

Desflurane and Surgery Exposure During Pregnancy Decrease Synaptic Integrity and Induce Functional Deficits in Juvenile Offspring Mice.

Anesthesia in pregnant women may cause adverse effects in the hippocampus of unborn babies and fetal brain development. The mechanisms underlying pathological changes resulting from anesthetics are unclear. This study tested the hypothesis that exposure to desflurane during pregnancy may impair cognition and memory functions of juvenile offspring.

Protective effects of GPR37 regulation of inflammation and multiple cell death pathways after ischemic stroke in mice.

GPCR 37 (GPR37) is a GPCR expressed in the CNS; its physiological and pathophysiological functions are largely unknown. We tested the role of GPR37 in the ischemic brain of GPR37 knockout (KO) mice, exploring the idea that GPR37 might be protective against ischemic damage. In an ischemic stroke model, GPR37 KO mice exhibited increased infarction and cell death compared with wild-type (WT) mice, measured by 2,3,5-triphenyl-2H-tetrazolium chloride and TUNEL staining 24 h after stroke.

Temporal Gene Expression Profiles after Focal Cerebral Ischemia in Mice.

A cascade of pathological processes is triggered in the lesion area after ischemic stroke. Unfortunately, our understanding of these complicated molecular events is incomplete. In this investigation, we sought to better understand the detailed molecular and inflammatory events occurring after ischemic stroke.

Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures.

Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone of normal and stroke mice.

Neurogenesis in the subventricular zone (SVZ) of the adult brain may contribute to tissue repair after brain injuries. Whether SVZ neurogenesis can be upregulated by specific neuronal activity in vivo and promote functional recovery after stroke is largely unknown. Using the spatial and cell type specific optogenetic technique combined with multiple approaches of in vitro, ex vivo and in vivo examinations, we tested the hypothesis that glutamatergic activation in the striatum could upregulate SVZ neurogenesis in the normal and ischemic brain.

Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice.

Focal cerebral ischemia results in an ischemic core surrounded by the peri-infarct region (penumbra). Most research attention has been focused on penumbra while the pattern of cell fates inside the ischemic core is poorly defined. In the present investigation, we tested the hypothesis that, inside the ischemic core, some neuronal and vascular cells could survive the initial ischemic insult while regenerative niches might exist many days after stroke in the adult brain.

Increased expression of the PI3K enhancer PIKE mediates deficits in synaptic plasticity and behavior in fragile X syndrome.

The PI3K enhancer PIKE links PI3K catalytic subunits to group 1 metabotropic glutamate receptors (mGlu1/5) and activates PI3K signaling. The roles of PIKE in synaptic plasticity and the etiology of mental disorders are unknown. Here, we show that increased PIKE expression is a key mediator of impaired mGlu1/5-dependent neuronal plasticity in mouse and fly models of the inherited intellectual disability fragile X syndrome (FXS).