Hippocampal cholinergic neurostimulating peptide (
HCNP) is known to promote differentiation of septohippocampal cholinergic neurons. The
HCNP precursor protein (
HCNP-pp) may play several roles, for example, as an
ATP-
binding protein,
a Raf kinase inhibitor
protein, and a
phosphatidylethanolamine-binding protein, as well as a precursor for
HCNP. This study therefore aimed to elucidate the involvement of
HCNP-pp in specific neural lineages after
stroke using a hypoxic-ischemic (HI) rat model of
brain ischemia. The specific neural lineages in the hippocampus were investigated 14 days after
ischemia. Some
bromodeoxyuridine (
BrdU)(+) neural progenitor cells in the hippocampus of hypoxic, HI, or
sham-operated rats expressed
HCNP-pp. Almost half of the
BrdU(+)/
HCNP-pp(+) cells also expressed the oligodendrocyte lineage marker
2',3'-cyclic nucleotide 3'-phosphodiesterase, whereas only a few
BrdU(+)/
HCNP-pp(+) cells in the hippocampus in HI brains expressed the neuronal lineage marker, doublecortin (DCX). Interestingly, no
BrdU(+)/
HCNP-pp(+) progenitor cells in hypoxic, HI, or
sham-operated brains expressed the astrocyte lineage marker,
glial fibrillary acidic protein. Together with previous in vitro data, the results of this study suggest that the expression level of
HCNP-pp regulates the differentiation of neural progenitor cells into specific neural lineages in the HI hippocampus, indicating that neural stem cell fate can be controlled via the
HCNP-pp mediating pathway.