Insufficient remyelination due to impaired oligodendrocyte precursor cell (OPC) differentiation and maturation is strongly associated with irreversible white matter injury (WMI) and neurological deficits. We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2 (LCN2) in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1 (EGR1) as the key signals contributing to LCN2-mediated insufficient OPC remyelination. In LCN-knockdown and OPC EGR1 conditional-knockout mice, we discovered enhanced OPC differentiation in developing and injured white matter (WM); consistent with this, the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical, acute WMI due to subarachnoid hemorrhage and typical, chronic WMI due to multiple sclerosis. This potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.
Mice ; Animals ; Remyelination/physiology* ; Oligodendrocyte Precursor Cells/metabolism* ; White Matter ; Subarachnoid Hemorrhage/metabolism* ; Lipocalin-2/metabolism* ; Early Growth Response Protein 1/metabolism* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Cell Differentiation/physiology* ; Brain Injuries/metabolism*

Objective To explore the effects of diethylenetriamine/nitric oxide (DETA/NO)on capillary spasm and early brain injury (EBI)after subarachnoid hemorrhage (SAH)in rats.Methods Sixty-nine male Sprague-dawley rats were randomized into three groups:sham group,SAH group and DETA/NO group.SAH model was established by wearing out the willis ring with thread and then Garcia neurological score was observed in the general animals.The expressions of alpha smooth muscle actin (αSMA)and PDGFRβwere detected by dual immunofluorescence staining;nitric oxide kit was used for detecting brain tissue NO concentration.Changes in the hemoglobin-stimulated capillaries were observed in rat slices.Results Three days after surgery,neurological deficit score was remarkably improved in DETA/NO group compared with that in SAH group (P<0 .0 5 ). Immunofluorescence results showed that the expressions of peri-capillaryαSMA and PDGFRβwere significantly increased after SAH (P<0.05 ),and that DETA/NO could down-regulate the expressions (P<0.05 ).NO concentration was greatly reduced about 3 hours after SAH and then gradually increased;DETA/NO could maintain the concentration of NO at an early stage (P<0 .0 5 ).The capillary contraction was observed in slices perfused with hemoglobin;DETA/NO could alleviate capillary spasm.Conclusion DETA/NO can alleviate the severity of capillary spasm and EBI after SAH in rats.

By genetic recombinant technique, the rat GDNF cDNA was recombinated to the retroviral vector pLXSN. The recombinant plasmid pLXSN-GDNF was verified by digestion with restriction endonucleases and PCR. Then neural stem cells (NSCs) were infected with pLXSN-GDNF. Immunocytochemistry, RT-PCR and western-blot were used to detect the transfection effect. Results showed that GDNF cDNA was cloned into retroviral vector pLXSN correctly, and the pLXSN-GDNF can infect NSCs efficiently. These results provide the possibility for transplantation and gene therapy with GDNF of nervous system diseases and injury.
Adenoviridae ; genetics ; Animals ; Cloning, Molecular ; DNA, Complementary ; genetics ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; genetics ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; Neurons ; cytology ; Rats ; Recombinant Proteins ; genetics ; Stem Cells ; cytology

Neurobiology is to study the structure,function,development and regeneration of the nervous system at molecular,cellular and whole level.The objective of neurobiological teaching is to explore the importont and difficult points in teaching' the present article attempts to design a project pattern in practical course of neurobiology,which is suited to learning mode of medical college students.

Objective To investigate the effects of chitin on the functional recovery after sciatic nerve axotomy. Methods Upon silicone-tubulization of the transected sciatic nerve in the adult rats, either 0.9% saline or 1% chitin solution was injected into the silicone chamber. The status of functional recovery of the injured sciatic nerve was observed by electrophysiological analysis, hydrogen-peroxide oxidoreductase (HRP) retrograde trace method, and axon morphometric analysis at 30 and 90 d respectively after sciatic nerve transection. Results ① Chitin shortened the latent period of CMAP by 1.79 ms and 1.29 ms, promoted the nerve conduction velocity by 16.00 m/s and 22.00 m/s, enhanced the amplitude by 8.17 mv and 12.42 mv, respectively, at 30 and 90 d after sciatic nerve transection (P

Objective To investigate the effects of ATP, suramin, ivermectin (IVM) and low pH value on pyramidal cells of rat hippocampus. Methods Pyramidal cells were rapidly dissociated from the hippocampus of 7-day postnatal rats by mechanical and enzymatic methods. Effects of ATP, suramin, IVM and low pH value on P2X receptor of neurons were studied by the technique of whole cell patch clamp. Results The transmembrane current was affected by ATP and suramin. There were different effects of IVM and low pH value on ATP induced current on different neurons. Conclusion There is extensive expression of P2X receptor on hippocampus pyramidal cells of rats. The expression of P2X receptors subunits are different among neurons.

Objective To investigate the expression of P2X receptors in CA1 subfield of rat hippocampus and the effect of hypoxia on the expression. Methods We set up the hypoxia animal model of high altitude and observed the expression of P2X receptors by using immunohistochemical staining before and after hypoxia. Results Immunohistochemistry showed that there were several sub-type of P2X receptors expressed in hippocampus CA1 neurons. After long term hypoxia, the expression of these receptors was increased. Conclusion there were abundant of P2X receptors expressed on the hippocampus CA1 neurons. Hypoxia affects the expression P2X receptors.

Objective To observe the expression and phosphorylation of N-methyl-D-aspartate (NMDA) receptor NR1 subunit in rat cortex and hippocampus under high altitude hypoxia. Methods The adult SD rats were exposed to hypobaric hypoxia imitating 5 500-meter high altitude for 8 h daily for 3, 7, 14, 21 d. Immunohistochemical staining, Western blotting and co-immunoprecipitation were used to detect the expression and phosphorylation of NR1 in rat cortex and hippocampus. Results Both immunohistochemistry and Western blotting showed NR1 expression in rat cortex and hippocampus was increased under hypoxia in a time-dependent manner. The tyrosine phosphorylation of hypoxia groups was increased, and reached the peak on day 14 after hypoxia, then decreased, still higher than that of control groups till day 21 (P

Objective To observe the time course of the changes in nitric oxide (NO) content and the activity of NO synthase (NOS) during hippocampal long term potentiation (LTP) in vitro . Methods The production and maintenance of LTP were detected by using extracelluar electrophysiological recording. NO content and NOS activity were determined by biochemical reaction. The expression of NOS mRNA was detected by in situ hybridization. Results Conditioning stimulation for 10 min induced LTP production and significant increases in NO content, NOS activity and expression of NOS mRNA. However, at 60 min after conditioning stimulation, LTP remained stably but NO content and NOS activity returned to the pre conditioning stimulation level. Moreover, the NOS mRNA was overexpressed at the early stage of LTP production. Conclusion Significant NO changes may occur at the early stage of LTP formation.