Metabolic Reprogramming in Gliocyte Post-cerebral Ischemia/ Reperfusion: From Pathophysiology to Therapeutic Potential.

Ischemic stroke is a leading cause of disability and death worldwide. However, the clinical efficacy of recanalization therapy as a preferred option is significantly hindered by reperfusion injury. The transformation between different phenotypes of gliocytes is closely associated with cerebral ischemia/ reperfusion injury (CI/RI). Moreover, gliocyte polarization induces metabolic reprogramming, which refers to the shift in gliocyte phenotype and the overall transformation of the metabolic network to compensate for energy demand and building block requirements during CI/RI caused by hypoxia, energy deficiency, and oxidative stress. Within microglia, the pro-inflammatory phenotype exhibits upregulated glycolysis, pentose phosphate pathway, fatty acid synthesis, and glutamine synthesis, whereas the anti-inflammatory phenotype demonstrates enhanced mitochondrial oxidative phosphorylation and fatty acid oxidation. Reactive astrocytes display increased glycolysis but impaired glycogenolysis and reduced glutamate uptake after CI/RI. There is mounting evidence suggesting that manipulation of energy metabolism homeostasis can induce microglial cells and astrocytes to switch from neurotoxic to neuroprotective phenotypes. A comprehensive understanding of underlying mechanisms and manipulation strategies targeting metabolic pathways could potentially enable gliocytes to be reprogrammed toward beneficial functions while opening new therapeutic avenues for CI/RI treatment. This review provides an overview of current insights into metabolic reprogramming mechanisms in microglia and astrocytes within the pathophysiological context of CI/RI, along with potential pharmacological targets. Herein, we emphasize the potential of metabolic reprogramming of gliocytes as a therapeutic target for CI/RI and aim to offer a novel perspective in the treatment of CI/RI.

New strategies for neuro protection in glaucoma.

Glaucoma is a progressive, irreversible loss of retinal ganglion cells (RGCs) and axons that results in characteristic optic atrophy and corresponding progressive visual field defect. The exact mechanisms underlying glaucomatous neuron loss are not clear. The main risk factor for glaucoma onset and development is high intraocular pressure (IOP), however traditional IOP-lowering therapies are often not sufficient to prevent degeneration of RGCs and the vision loss may progress, indicating the need for complementary neuroprotective therapy. This review summarizes the progress for neuro protection in glaucoma in recent 5 years, including modulation of neuroinflammation, gene and cell therapy, dietary supplementation, and sustained-release system.

Calcium Salt of N-(5-Hydroxynicotinoyl)-L-Glutamic Acid Weakens Depressive-Like Behavior and Parkinsonian Syndrome in Experiment on Rodents.

We studied antidepressant and antiparkinsonian properties of N-(5-hydroxynicotinoyl)-Lglutamic acid calcium salt (Ampasse) in rodents. It was found that Ampasse in a dose of 30 mg/kg exhibited antidepressant activity in the forced swimming test in mice and in a dose of 0.1 mg/kg maximally alleviates the symptoms of parkinsonian syndrome induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57Bl/6 mice, and haloperidol-induced catalepsy in rats.

Reversal of TRESK Downregulation Alleviates Neuropathic Pain by Inhibiting Activation of Gliocytes in the Spinal Cord.

Despite the consensus that activation of TWIK-related spinal cord K+ (TRESK) might contribute to the pathogenesis of chronic pain, the specific mechanisms underlying the transfer and development of pain signals still remain obscure. In the present study, we validated that TRESK was expressed in neurons instead of glial cells. Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately. Compared with SNI rats, intrathecal injection of TRESK gene recombinant adenovirus significantly downregulated the expression levels of Cx36 and Cx43 and suppressed the activation of gliocytes in the spinal cord, with hyperalgesia significantly reduced. In conclusion, TRESK contributes to the pathogenesis of NP by upregulation of synaptic transmission and activation of gliocytes.

Correlation of iron deposition and change of gliocyte metabolism in the basal ganglia region evaluated using magnetic resonance imaging techniques: an in vivo study.

INTRODUCTION: We assessed the correlation between iron deposition and the change of gliocyte metabolism in healthy subjects' basal ganglia region, by using 3D-enhanced susceptibility weighted angiography (ESWAN) and proton magnetic resonance spectroscopy ((1)H-MRS). MATERIAL AND METHODS: Seventy-seven healthy volunteers (39 female and 38 male subjects; age range: 24-82 years old) were enrolled in the experiment including ESWAN and proton MRS sequences, consent for which was provided by themselves or their guardians. For each subject, the mean phase value gained by ESWAN was used to evaluate the iron deposition; choline/creatine (Cho/Cr) and mI/Cr ratios gained by (1)H-MRS were used to evaluate gliocyte metabolism in the basal ganglia region of both sides. The paired t test was used to test the difference between the two sides of the basal ganglia region. Linear regression was performed to evaluate the relation between mean phase value and age. Pearson's correlation coefficient was calculated to analyze the relationship between the result of ESWAN and (1)H-MRS. RESULTS: There was no difference between the two sides of the basal ganglia region in the mean phase value and Cho/Cr. But in mI/Cr the mean phase value of each nucleus in bilateral basal ganglia decreased with increasing age. There are 16 r-values between the mean phase value and Cho/Cr and mI/Cr in bilateral basal ganglia region. And each of all p-values is less than 0.001 (p < 0.001). CONCLUSIONS: Iron deposition in the bilateral basal ganglia is associated with the change of gliocyte metabolism with increasing age. Iron deposition in each nucleus of the basal ganglia region changes with age.

A novel primary culture and identification method of human retina gliocyte / 中华实验眼科杂志

BackgroundHuman retinal gliocytes play an important role in proliferative diseases,which are the basis of in vitro studies.Researchers have cultured human retinal gliocytes in the past.In our study,we found that the cells we cultured presented a unique shape different from those by other researchers.ObjectiveThis study was to design to produce a new culture and purification method for retinal gliocyte in vitro.Methods Retinal tissue was isolated from human eyeballs and digested using the two-step digestion method (2％ pancreatin and 0.133％collagenase Ⅵ) to harvest the retinal glio cytes.The cells were collected and cultured in endothelial cell-targeted nutrient culture containing 10％ fetal calf serum and supplemented with β-endothelial cell growth factor (ECGF) and sodium heparin,and the culture dishes were coated with fibronectin(FN) to promote the attachment of retinal gliocyte.During the culturing process,the gliocytes were identified by the observation of morphological characteristic and regular histological examination.The identification of the cells also was performed by immunochemistry targeting glial fibrillary acidic protein (GFAP),Vimentin,neuron specific enolase ( NSE ),S-100,CD34,and Ⅷ factor.Results Retinal gliocytes were isolated successfully from the human retina by the two-step digestion method.Primary cultured cells attached after 72 hours and achieved confluency between day 9 and 10 that were aligned petaliform in shape.Regular histological examination after H&E staining showed blue cell nuclei and light red cytoplasm.The target cells presented with strong responses for GFAP and Vimentin and no response for NSE,S-100,CD34 and Ⅷ factor.ConclusionsLarge amount of purified human retinal gliocytes can be obtained by two-step digestion and cultured in endothelial cells-targeted culture medium supplemented with β-ECGF and sodium heparin in plates coated with FN.The cultured cells expressed markers for retinal gliocytes.However,specific features of these cells remain to be further elucidated.

THE EFFECTS OF DIFFERENT INDUCERS ON THE DIFFERENTIATION OF NONHEMATOPOIETIC STEM CELLS INTO NERVE CELLS IN HUMAN UMBILICAL CORD BLOOD (HUCB) / 解剖学报

GFAP.Conclusion RA is the best factor for neurons and astroglia,and RA+EGF+bFGF are the best for oligodendrocytes.