Neural stem cells have been found in neurogenic brain regions like the hippocampus, subventricular zone (SVZ), olfactory bulb and in some non-neurogenic regions, i.e. spinal cord. Novel stem cell niches, hosting stem/progenitor cells with neural differentiation potential have also been identified in rat leptomeninges. Immunocytochemical data have revealed nestin-positive cells that did not follow the astrocyte (glial fibrillary acidic proteins, GFAP-), or vascular (integral membrane chondroitin sulphate proteoglycan, NG2-) profiles. Such cells are present from embryonic stages up to adulthood. Tissue extracts with nestin-positive cells can be cultured and expanded in vitro, both as neurospheres and cell populations with stem cell features. Neurospheres are similar to the SVZ-derived neurospheres in terms of multipotency and gene expression. Cultured cells also have the capacity to form synaptic connections. Preliminary electrophysiological profiles of expanded cells were examined at 15 days in vitro. Whole-cell patch-clamp recordings, revealed mostly incomplete functional development, with an early neuron-like appearance. Small rudimentary action potentials were generated by the majority of cells in response to incremental injected depolarizing current steps, starting from a holding potential of -60 mV. Fast overshooting action potentials with a mature configuration characterize mature neurons. Current-voltage relationships revealed various electrophysiological properties, but mainly outward membrane rectification.

Based on the presence or absence of rectification when depolarizing step currents were applied, two basic cell types were observed: the majority of cells were classified as Type I, primarily associated with outward rectification; Type II cells had linear responses to step currents. MAP2-positive cells expressed GluR2 subunits of the ionotropic AMPA-glutamate receptor as well as the glutamate decarboxylase (GAD67), marker of GABAergic neurons. Exogenously-applied glutamate or GABA at 100 mM elicited postsynaptic responses. These data suggest that rat leptomeningeal stem cells can differentiate into fully functional neurons.