D30 Alleviates β2-Microglobulin-Facilitated Neurotoxic Microglial Responses in Isoflurane/Surgery-Induced Cognitive Dysfunction in Aged Mice.

Postoperative cognitive dysfunction (POCD) is a common complication with no effective treatment in elderly patients. POCD, Alzheimer disease (AD), and many other cognitive diseases mostly involve neurotoxic microglia response, and recently, β2-microglobulin (B2M) has been suggested to play a pivotal role. A novel pyromeconic acid-styrene hybrid compound D30 was synthesized by our team and shown to be safe and effective in some neurodegenerative mouse models.

NeuroD1 administration ameliorated neuroinflammation and boosted neurogenesis in a mouse model of subarachnoid hemorrhage.

Background: Subarachnoid hemorrhage (SAH) causes significant long-term neurocognitive dysfunction, which is associated with hippocampal neuroinflammation. Growing evidences have shown that astrocytes played a significant role in mediating neuroinflammation. Recently, in vivo reprogramming of astrocytes to neurons by NeuroD1 or PTBP1 administration has generated a lot of interests and controversies.

Astrocytic connexin 43 deletion ameliorates SNI-induced neuropathic pain by reducing microglia activation.

Neuropathic pain (NP) is a chronic disease caused by damage to the peripheral or central nervous system. Connexin 43 (Cx43), the primary connexin expressed by astrocytes, has been reported to be significantly increased in NP. However, the roles and mechanisms of Cx43 in the development and maintenance of NP remain largely unknown, while microglia activation has been commonly regarded as a key factor of NP.

Bexarotene enhances astrocyte phagocytosis via ABCA1-mediated pathways in a mouse model of subarachnoid hemorrhage.

Background And Purpose: Enhancing phagocytosis can facilitate the removal of inflammatory molecules, limit the toxicity of dead cells and debris, and promote recovery after brain injury. In this study, we aimed to explore the role of bexarotene (Bex), a retinoid X receptor (RXR) agonist, in promoting astrocyte phagocytosis and neurobehavioral recovery after subarachnoid hemorrhage (SAH).

Methods: Mice SAH model was induced by pre-chiasmatic injection of blood.

Nestin+/CD31+ cells in the hypoxic perivascular niche regulate glioblastoma chemoresistance by upregulating JAG1 and DLL4.

Background: Failure of glioblastoma (GBM) therapy is often ascribed to different types of glioblastoma stem-like cell (GSLC) niche; in particular, a hypoxic perivascular niche (HPVN) is involved in GBM progression. However, the cells responsible for HPVNs remain unclear.

Methods: Immunostaining was performed to determine the cells involved in HPVNs.

Dual pathways mediate β-amyloid stimulated glutathione release from astrocytes.

Oxidative stress plays an important role in the progression of Alzheimer's disease (AD) and other neurodegenerative conditions. Glutathione (GSH), the major antioxidant in the central nervous system, is primarily synthesized and released by astrocytes. We determined if β-amyloid (Aβ42), crucially involved in Alzheimer's disease, affected GSH release.

Cell-density-dependent manifestation of partial characteristics for neuronal precursors in a newly established human gliosarcoma cell line.

Gliosarcoma cell line K308 was established from a primary tumor specimen removed from a 51-year-old male Han Chinese patient. Besides the typical characteristics of gliosarcoma cells, K308 cells express abundant glutaminase and can release large amount of glutamate. K308 exhibited cell-density-dependent expression of neuronal precursor markers, particularly nestin.

Activation, permeability, and inhibition of astrocytic and neuronal large pore (hemi)channels.

Astrocytes and neurons express several large pore (hemi)channels that may open in response to various stimuli, allowing fluorescent dyes, ions, and cytoplasmic molecules such as ATP and glutamate to permeate. Several of these large pore (hemi)channels have similar characteristics with regard to activation, permeability, and inhibitor sensitivity. Consequently, their behaviors and roles in astrocytic and neuronal (patho)physiology remain undefined.

Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.

Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function.

Novel hypoglycemic injury mechanism: N-methyl-D-aspartate receptor-mediated white matter damage.

Objective: Hypoglycemia is a common adverse event and can injure central nervous system (CNS) white matter (WM). We determined whether glutamate receptors were involved in hypoglycemic WM injury.

Methods: Mouse optic nerves (MON), CNS WM tracts, were maintained at 37°C with oxygenated artificial cerebrospinal fluid (ACSF) containing 10mM glucose.

Identification of glutathione S-transferase pi as a protein involved in Parkinson disease progression.

Parkinson disease (PD) typically affects the cortical regions during the later stages of disease, with neuronal loss, gliosis, and formation of diffuse cortical Lewy bodies in a significant portion of patients with dementia. To identify novel proteins involved in PD progression, we prepared synaptosomal fractions from the frontal cortices of pathologically verified PD patients at different stages along with age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique.

Pharmacological "cross-inhibition" of connexin hemichannels and swelling activated anion channels.

The study of ion channels has relied heavily on the use of pharmacological blocking agents. However, many of these agents have multiple effects, which may compromise interpretation of results when the affected mechanisms/pathways mediate similar functions. Volume regulated anion channels (VRAC) and connexin hemichannels can both mediate the release of glutamate and taurine, although these channels have distinct activation stimuli and hemichannels, but not VRAC, are permeable to Lucifer Yellow (LY).

White matter vulnerability to ischemic injury increases with age because of enhanced excitotoxicity.

Stroke incidence increases with age and this has been attributed to vascular factors. We show here that CNS white matter (WM) is intrinsically more vulnerable to ischemic injury in older animals and that the mechanisms of WM injury change as a function of age. The mouse optic nerve was used to study WM function.

Excitotoxic mechanisms of ischemic injury in myelinated white matter.

Axonal injury and dysfunction in white matter (WM) are caused by many neurologic diseases including ischemia. We characterized ischemic injury and the role of glutamate-mediated excitotoxicity in a purely myelinated WM tract, the mouse optic nerve (MON). For the first time, excitotoxic WM injury was directly correlated with glutamate release.

Functional connexin "hemichannels": a critical appraisal.

"Hemichannels" are defined as the halves of gap junction channels (also termed connexons) that are contributed by one cell; "hemichannels" are considered to be functional if they are open in nonjunctional membranes in the absence of pairing with partners from adjacent cells. Several recent reviews have summarized the blossoming literature regarding functional "hemichannels", in some cases encyclopedically. However, most of these previous reviews have been written with the assumption that all data reporting "hemichannel" involvement really have studied phenomena in which connexons actually form the permeability or conductance pathway.

Sensitization to brain antigens after stroke is augmented by lipopolysaccharide.

After stroke, the blood-brain barrier is transiently disrupted, allowing leukocytes to enter the brain and brain antigens to enter the peripheral circulation. This encounter of normally sequestered brain antigens by the systemic immune system could therefore present an opportunity for an autoimmune response to brain to occur after stroke. In this study, we assessed the immune response to myelin basic protein (MBP) in animals subjected to middle cerebral artery occlusion (MCAO).

Functional hemichannels in astrocytes: a novel mechanism of glutamate release.

Little is known about the expression and possible functions of unopposed gap junction hemichannels in the brain. Emerging evidence suggests that gap junction hemichannels can act as stand-alone functional channels in astrocytes. With immunocytochemistry, dye uptake, and HPLC measurements, we show that astrocytes in vitro express functional hemichannels that can mediate robust efflux of glutamate and aspartate.

Modulation of glial glutamate transport through cell interactions with the extracellular matrix.

Glial glutamate transport plays a pivotal role in maintaining glutamate homeostasis in the central nervous system. Expression of glutamate transporters is highly regulated during brain development, and a number of pathological conditions are associated with deficits in expression and/or function of glutamate transports. While several soluble factors have been shown to regulate the expression of glutamate transporter, the contribution of cell-cell interaction and cell-environmental interaction in the regulation of glutamate transport is unknown.