Toll-like receptor 4 (TLR4) mediates brain damage after
stroke. Now our objective is to determine TLR4 involvement in
stroke-induced neurogenesis.
Stroke was induced by permanent
middle cerebral artery occlusion in wild-type and TLR4-deficient mice. Stereological and densitometric analysis of immunofluorescence-labeled brain sections and FACS analysis of cell
suspensions were performed. Our results show that subventricular zone (SVZ) cell proliferation after
stroke depends on
infarct size. Second, when comparing brains with similar lesions, TLR4 attenuated SVZ proliferation, as shown by a decrease in
prominin-1(+)/EGFR(+)/
nestin(-) cells (type-C cells) at 1-2 d, and in
BrdU(+) cells at 7 d, in TLR4(+/+) vs. TLR4(-/-) mice. Interestingly, 7 d after the
infarct, neuroblasts in TLR4(+/+) mice migrated farther distances, reaching areas closer to the lesion than those in TLR4-deficient mice. However, at 14 d, TLR4-deficient mice presented a higher number of neuroblasts in all migratory zones than the TLR4(+/+) counterparts, which suggests that TLR4 deficiency delays neuroblast migration. Consistently, TLR4(+/+) mice showed an increased number of interneurons (NeuN(+)/
BrdU(+)/GAD67(+) cells) in peri-
infarct cortex 14-28 d after
stroke. Our data indicate that, despite a negative effect on SVZ cell proliferation, TLR4 plays an important role in
stroke-induced neurogenesis by promoting neuroblasts migration and increasing the number of new cortical neurons after
stroke.