Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.
Humans ; Astrocytes/pathology* ; Chronic Pain/pathology* ; Neuroglia/physiology* ; Neurons/physiology* ; Synaptic Transmission ; Chronic Disease

Diabetes patients tend to have the gastrointestinal motility disorder. Although the relationship between the motility disorder and both the neurons and Cajal cells in the enteric nervous system (ENS) is well established, little is known about the role of enteric glial cells (EGCs) in gastric motility in diabetes. This study aimed to examine the expression of the glial marker S100B and morphology of EGCs in gastric tissues and the relationship between activated EGCs and the damage of gastric emptying in diabetic models. The diabetic model of rat was induced with 1% streptozotocin (STZ). The model rats at 7-14 days and at 56-63 days were defined as early diabetic rats and advanced diabetic rats, respectively, and normal rats at the two time periods served as their corresponding controls. The gastric emptying rate of the rats was tested by using the phenol red solution. The ultrastructure of EGCs in the gastric antrum was observed by the transmission electron microscopy, and the expression of S100B in the myenteric plexus was immunohistochemically detected. The results showed that the gastric emptying rate was significantly increased in the early diabetic rats and decreased in the advanced diabetic rats when compared with their corresponding control rats (P<0.01 for both). The ultrastructure of EGCs was mostly normal in both the early diabetic and control groups. Vacuolization of mitochondria and expansion of endoplasmic reticulum occurred in both the advanced diabetic group and its control group, and even the structure of smooth muscle cells and intestinal neurons was destroyed in the advanced diabetic group. The expression level of S100B in the advanced diabetic group was significantly decreased compared with its control group (P<0.05). It was obviously increased in the early diabetic control group when compared with the advanced diabetic control group (P<0.05). However, there was no significant difference in the S100B expression between the early diabetic group and its control group (P>0.05). The findings suggested that the gastric motility dysfunction in diabetes may be associated with the changes of morphology and number of EGCs in the myenteric plexus.
Animals ; Diabetes Mellitus, Experimental ; pathology ; Gastrointestinal Motility ; physiology ; Male ; Neuroglia ; pathology ; Rats ; Rats, Sprague-Dawley

Glial scar formed by central nervous system (CNS) injury is the main inhibitory barrier of nerve regeneration. How to promote axonal regeneration after injury,how to accelerate neural network reconstruction and how to improve brain function recovery have become a hot problem to be solved in the field of neuroscience. This article focuses on the recent advances of therapeutic strategies for axonal regeneration.
Animals ; Astrocytes ; pathology ; Brain Injuries ; pathology ; physiopathology ; Cicatrix ; prevention & control ; Humans ; Nerve Regeneration ; Neuroglia ; pathology ; Neuronal Plasticity ; physiology ; Neurons ; physiology ; Proteoglycans ; metabolism ; Spinal Cord Injuries ; pathology ; physiopathology

Apoptosis ; Extracellular Matrix Proteins ; metabolism ; Glaucoma ; pathology ; Glutamic Acid ; metabolism ; Humans ; Neuroglia ; pathology ; physiology ; Nitric Oxide Synthase ; physiology ; Optic Nerve ; physiology ; Optic Nerve Diseases ; pathology ; Retinal Ganglion Cells ; pathology ; Tumor Necrosis Factor-alpha ; physiology

Neurogenesis can be induced by pathological conditions such as cerebral ischemia. However the molecular mechanisms or modulating reagents of the reactive neurogenesis after the cerebral ischemia are poorly characterized. Retinoic acid (RA) has been shown to increase neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain neuroblasts. Here, we examined whether RA can modulate the reactive neurogenesis after the cerebral ischemia. In contrast to our expectation, RA treatment decreased the reactive neurogenesis in subventricular zone (SVZ), subgranular zone (SGZ) and penumbral region. Furthermore, RA treatment also decreased the angiogenesis and gliosis in penumbral region.
Animals ; Brain/blood supply ; Cell Differentiation ; Cell Proliferation ; Ischemic Attack, Transient/metabolism/*pathology ; Male ; Neovascularization, Pathologic ; Neuroglia/pathology/physiology ; Neurons/pathology/*physiology ; Rats ; Rats, Sprague-Dawley ; Tretinoin/*pharmacology/physiology

OBJECTIVEInducible nitric oxide synthase (iNOS) is a main rate-limiting enzyme resulting in over-production of nitric oxide following hypoxia-ischemia (HI). The aim of this study was to observe the expression of iNOS protein and gliacyte apoptosis in the brains of premature rats after HI, in order to explore possible relationships of iNOS with white matter damage (WMD).

METHODSOne hundred and twelve 2-day-old premature rats were randomly subjected to right carotid ligation followed by 4 hrs hypoxic stress (WMD group) or sham operation (control group). The pups were sacrificed at 1, 3, 6, 12 hrs, and 1, 3 and 7 days after HI. Immunohistochemical technique was applied to determine the iNOS expression in periventricular white matter tissues. Gliacyte apoptosis was detected in these tissues by TUNEL.

RESULTSCompared with the control group, iNOS expression began to increase 1 hr after HI and reached the peak 1 day after HI in the WMD group. Gliacyte apoptosis increased 1 hr after HI and peaked 1 day after HI in the WMD group compared with the control group.

CONCLUSIONSIn the neonatal rats with WMD, the expression of iNOS may be involved in the ischemic cellular events including apoptosis, and plays a role in the pathophysiological process of WMD.

Animals ; Animals, Newborn ; Apoptosis ; Brain ; pathology ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; In Situ Nick-End Labeling ; Leukoencephalopathies ; metabolism ; pathology ; Neuroglia ; pathology ; Nitric Oxide ; physiology ; Nitric Oxide Synthase Type II ; analysis ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study in vivo the endogenous self-repair mechanism in immature white matter induced by ischemia in neonatal rats with periventricular leukomalacia (PVL).

METHODSFive-day-old neonatal Sprague-Dawley (SD) rats were randomly divided into sham and PVL groups. Rat model of PVL was prepared by ligation of the right common carotid artery following 2 hours of exposure to 8% oxygen. Pathological changes and myelination in the white matter were assessed under light and electron microscopy at 7 and 21 days after PVL. O4-positive OL precursor cells in the white matter were determined with immunofluorescence staining. Activation, proliferation, migration and differentiation of glial progenitor cells in SVZ were observed using immunofluorescent double labeling of either NG2 (marker of progenitor cells) and 5-bromodeoxyuridine (BrdU), or O4 (marker of OL precursor cells) and BrdU.

RESULTSAll rats in the PVL group manifested either mild or severe white matter injury under light microscopy, and had higher pathological scores of white matter compared with the sham group at 7 and 21 days after PVL (P<0.05). Electron microscopy showed that the number and thickness of myelin sheath in the PVL group were significantly reduced compared with the sham group (P<0.01). O4-positive OL precursor cells in the white matter observed under fluorescence microscopy were significantly reduced in the PVL group compared with the sham group (P<0.05). BrdU/NG2-positive cells in the SVZ increased significantly in the PVL group 48 hours after PVL and migrated into the periventricular area, reaching a peak on day 7 after PVL. BrdU/O4-positive newborn cells began to appear in the periventricular area 72 hours after PVL, and the number of BrdU/O4-positive cells in the PVL group was statistically more than in the sham group on day 21 after PVL (P<0.05).

CONCLUSIONSIschemia may induce brain self-repair in neonatal rats, resulting in activation and proliferation of NG2 glial progenitor cells in the SVZ migration and differentiation into OL precursor cells in periventricular white matter.

Animals ; Animals, Newborn ; Brain ; pathology ; Brain Ischemia ; pathology ; Bromodeoxyuridine ; metabolism ; Cell Differentiation ; Disease Models, Animal ; Humans ; Infant, Newborn ; Leukomalacia, Periventricular ; pathology ; Myelin Sheath ; physiology ; Neuroglia ; pathology ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; pathology

The expression of two intermediate filaments, nestin and vimentin, was studied in spinal cord injury (SCI) to elucidate their roles in the formation of glial scars. Rats were sacrificed 1, 4, and 7 days after induction of compression injury of the spinal cord using an aneurysm clip. The affected spinal cords were studied using antibodies against nestin and vimentin intermediate filaments. One day after spinal cord injury, some clusters of nestin-positive vessels were detected in the center of the injury, but few were seen in other cell types. Vimentin immunostaining was detected in some glial cells in the center and its level of immunoreactivity was enhanced in the ependymal cells of the central canal. On days 4 and 7 after spinal cord injury, astrocytes and some ependymal cells in the central canal were stained positively for nestin and increased expression of nestin was observed in vessels. Vimentin was detected in some macrophages and astrocytes in the lesions. Nestin was co-localized with glial fibrillary acidic protein in some glial cells in SCI. These findings imply that spinal cord cells in adult animals have embryonic capacity, and these cells are activated after injury, which in turn contributes to repair of spinal cord injury through formation of a glial scar.
Animals ; Cicatrix/pathology ; Glial Fibrillary Acidic Protein/analysis ; Immunohistochemistry ; Intermediate Filament Proteins/analysis ; Intermediate Filaments/*physiology ; *Nerve Tissue Proteins ; Neuroglia/*pathology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries/*pathology ; Vimentin/analysis

OBJECTIVETo investigate the involvement of bone marrow stem cell-derived astrocytes (BMDSCs) in the formation of glia limitans after brain injury.

METHODSIn a female SD rat model of brain injury, green fluorescence protein (GFP)-labeled BMDSCs from male SD rats were transplanted via the caudal vein 24 h after the injury. The rats were sacrificed at 2, 4 and 8 weeks after the transplantation, and immunohistochemistry for glial fibrillary acidic protein (GFAP) was performed to observe the astrocytes. The fluorescence emitted by GFP was observed to identify the presence of the bone marrow-derived stem cells, and the GFAP(+)/GFP(+) cells in the glia limitnas were detected under fluorescence microscopy. RESULTS The GFAP(+)/GFP(+) cells were found in the glia limitans between the brain lesion and normal brain tissue.

CONCLUSIONBone marrow stem cell-derived astrocytes is involved in glia limitans formation after brain injury, which can be of significance in brain injury recovery and implantation of engineered materials.

Animals ; Astrocytes ; cytology ; physiology ; Bone Marrow Cells ; cytology ; metabolism ; Brain Injuries ; pathology ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Green Fluorescent Proteins ; Male ; Mesenchymal Stromal Cells ; cytology ; Neuroglia ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.
Animals ; Astrocytes/cytology* ; Axons/physiology* ; Cell Transplantation ; Disease Models, Animal ; Electric Stimulation ; Humans ; Microglia/cytology* ; Motor Neurons/cytology* ; Nerve Regeneration ; Neuroglia/cytology* ; Neuronal Plasticity ; Neurons/cytology* ; Oligodendroglia/cytology* ; Pyramidal Tracts/pathology* ; Recovery of Function ; Regenerative Medicine/methods* ; Spinal Cord Injuries/therapy*