Abstract
The present study aimed to investigate a possibility of brain repair from diseased or damaged disorders mediated by cell-free filtrate of neural stem cell (NSC) lysates (FNSCL). Mouse NSCs were isolated from the brains of embryos at 15 day postcoitum (dpc). The expression of the Nestin was examined by immunocytochemical technique. Sonication of NSCs cultured and nestin-positive was performed in a bath-type sonicator, and the cell-free filtrate was recovered from a filtrative step of the lysates. The animals in the monosodium glutamate MSG group received intragastric(ig) administration of MSG (2.0 g/kg per day) for 10 days the animals in the MSG+NSCs and MSG+FNSCL groups received intracerebroventricular transplantation of 10 ?l of NSC suspension, approximately 1.0×105 cells, or intracerebroventricular injection of 10 ?l of cell-free filtrate of lysates of approximately 1.0×105 NSCs on day 1 and day 11 after 10-d MSG exposure, respectively. The mice in control and MSG group were intracerebroventricularly administered with 10 ?l of DMEM instead of NSCs or FNSCL. On 11 day after intracerebroventricular transplantation of NSCs or intracerebroventricular injection of FNSCL, the test of Y-maze discrimination learning were performed, and then the histopathology of the animal brains was studied, to analyze MSG-induced functional and morphological changes and the effects of intracerebroventricular transplantation of NSCs or intracerebroventricular injection of FNSCL on the brain repair from MSG-induced excitotoxic injury. Both intracerebroventricular transplantation of NSCs and intracerebroventricular injection of FNSCL facilitated the brain repair following glutamate-induced excitotoxic injury in adult mice, suggesting that there are certain NSC factors inside NSCs which are effective in repairing glutamate-induced excitotoxic brain injury. Administration of FNSCL might be a cell-free-based therapeutic strategy to repair diseased or damaged central nervous system CNS tissue.
Highlights
Exitotoxicity, a pathological process by which neural cells are damaged by overstimulation of its membrane receptors due to excessive exposure to the neurotransmitter glutamate, has been implicated as one of the key factors contributing to neuronal injury and death in a wide range of both acute and chronic neurodegenerative disorders
Using an experimental model of excitotoxic brain injury following exposure to glutamate, we demonstrated that both intracerebroventricular transplantation of neural stem cell (NSC) andt intracerebroventricular injection of FNSCL facilitated the brain repair following glutamate-induced excitotoxic injury in adult mice
The results suggest that both intracerebroventricular NSC transplantation and intracerebroventricular injection of FNSC facilitated nearly the repair of brain structure following glutamate-induced excitotoxic injury in adult mice, suggesting that there are certain NSC factors inside NSCs which are effective in repairing glutamate-induced excitotoxic brain injury
Summary
Exitotoxicity, a pathological process by which neural cells are damaged by overstimulation of its membrane receptors due to excessive exposure to the neurotransmitter glutamate, has been implicated as one of the key factors contributing to neuronal injury and death in a wide range of both acute and chronic neurodegenerative disorders. We sucessfully established an experimental model of excitotoxic brain injury following exposure to glutamate, in which ig excessive administration of MSG results in a series of behavioral disorders, and obvious histopathological brain lesion in adult mice [4]. Cells for transplantation must be nontransformed, well characterized, able to migrate toward sites of diseased or damaged CNS tissues, and able to differentiate into the appropriate cell types. Cultures containing human neural stem and progenitor cells (neurospheres) have the capacity to proliferate and differentiate into the major phenotypes of the adult brain. These properties make them optimal candidates for therapeutic transplantation in cases of neurological diseases that involve cell loss. Stem cell transplantation through cell replacement or as vector for gene delivery is a potential strategy for the treatment of neurodegenerative diseases [5]
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