Downregulation of P2X7 receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia.

Oligodendrocyte precursor cells (OPCs) are the predominant oligodendrocyte-lineage stage in the cerebral hemispheres of neonatal rat. Prior studies have shown that OPCs are highly vulnerable to hypoxic-ischemic injury, yet the mechanisms are not well understood. P2X(7) receptor (P2X(7)R) is an ATP-gated ion channel that has unusual properties and plays very complex roles in a variety of neuropathologic conditions. However, little is known about the involvement of P2X(7)R in OPCs development and injury. The present study was aimed at examining the presence of P2X(7)R in OPCs and evaluating the change of the receptor expression after hypoxia ischemia. Using Immunofluorescence, RT-PCR, and western blot analysis, we demonstrated that OPCs expressed P2X(7)R in vitro and in vivo. Activation of P2X(7)R in OPCs in response to 3'-O-(4-benzoyl) benzoyl-ATP (BzATP) led to an increased mobilization of intracellular calcium [Ca(2+)]i, formation of large pores and cell death. These functional responses were sensitive to pretreatment of cells with the P2X(7)R antagonist, Brilliant Blue G (BBG, 100 nM), which was a selective antagonist for P2X(7)R in nanomole range. A decrease in P2X(7)R expression was observed in cultured OPCs after exposure to oxygen-glucose deprivation (OGD) for 2 h in vitro. Using a neonatal hypoxic-ischemic injury model in postnatal 3 rats, the similar downregulation was also detected in ischemic cerebral cortex, subcortical white matter and hippocampus compared with sham operation controls. In conclusion, the present data demonstrated that OPCs expressed functional P2X(7)R. The post-ischemic downregulation of P2X(7)R suggested a role for this receptor in the pathophysiology of hypoxic-ischemic brain injury.

A morphological and electrophysiological study on the postnatal development of oligodendrocyte precursor cells in the rat brain.

A widespread population of cells in CNS is identified by specific expression of the NG2 chondroitin sulphate proteoglycan and named as oligodendrocyte precursor cell (OPC). OPCs may possess stem cell-like characteristics, including multipotentiality in vitro and in vivo. It was proposed that OPCs in the CNS parenchyma comprise a unique population of glia, distinct from oligodendrocytes and astrocytes. This study confirmed that NG2 immunoreactive OPCs were continuously distributed in cerebral cortex and hippocampus during different postnatal developmental stages. These cells rapidly increased in number over the postnatal 7 days and migrate extensively to populate with abundant processes both in developing cortex and hippocampus. The morphology of OPCs exhibited extremely complex changes with the distribution of long distance primary process gradually increased from neonatal to adult CNS. Immunohistochemical studies showed that OPCs exhibited the morphological properties that can be distinguished from astrocytes. The electrophysiological properties showed that OPCs expressed a small amount of inward Na(+) currents which was distinguished from Na(+) currents in neurons owing to their lower Na-to-K conductance ratio and higher command voltage step depolarized maximum Na(+) current amplitude. These observations suggest that OPCs can be identified as the third type of macroglia because of their distribution in the CNS, the morphological development in process diversity and the electrophysiological difference from astrocyte.

Poly-lactic acid and agarose gelatin play an active role in the recovery of spinal cord injury.

Objective To investigate the role of poly-lactic acid and agarose gelatin in promoting the functional recovery of the injured spinal cord. Methods Poly-lactic acid (PLA) or agarose was embedded in the space between two stumps of the hemisectioned spinal cord. Immunohistochemistry was used to show astroglia proliferation and the infiltration of RhoA-positive cells. Locomotor activity recovery was evaluated by testing the function of hindlimbs. Results Astroglias and RhoA labeled non-neuronal cells accumulated in the area adjacent to the implant, while the number of RhoA-positive cells was decreased dramatically in the absence of implant. Animals implanted with agarose gelatin recovered more quickly than those with PLA, concomitant with a higher survival rate of the neurons. Conclusion Both PLA and agarose gelatin benefited the recovery of spinal cord after injury by providing a scaffold for astroglia processes. Modulation of the rigidity, pore size and inner structure of PLA and agarose gelatin might make these biodegradable materials more effective in the regeneration of the central nervous system (CNS).