RT Journal Article
T1 Toll‐like receptor 4 modulates cell migration and cortical neurogenesis after focal cerebral ischemia
A1 Moraga Yébenes, Ana
A1 Pradillo Justo, Jesús Miguel
A1 Cuartero Desviat, María Isabel
A1 Hernández Jiménez, Macarena
A1 Oses, Marta
A1 Moro Sánchez, María Ángeles
A1 Lizasoaín Hernández, Ignacio
AB 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.
PB Wiley [Commercial Publisher]
SN 0892-6638
YR 2014
FD 2014-07-25
LK https://hdl.handle.net/20.500.14352/95720
UL https://hdl.handle.net/20.500.14352/95720
LA eng
DS Docta Complutense
RD 6 abr 2025