Toll‐like receptor 4 modulates cell migration and cortical neurogenesis after focal cerebral ischemia. Issue 11 (25th July 2014)

• Record Type: Journal Article
• Authors: Moraga, Ana; Pradillo, Jesús M.; Cuartero, María I.; Hernández‐Jiménez, Macarena; Oses, Marta; Moro, María A.; Lizasoain, Ignacio
• Is Part Of: FASEB journal. Volume 28:Issue 11(2014)
• Page Start: 4710
• Page End: 4718
• Publication Date: 2014-07-25
• Subjects: innate immunity -- neuroblast -- proliferation -- stroke; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.14-252452
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract : 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.—Moraga, A., Pradillo, J. M., Cuartero, M. I., Hernández‐Jiménez, M., Oses, M., Moro, M. A., Lizasoain, I., Toll‐like receptor 4 modulates cell migration and cortical neurogenesis after focal cerebral ischemia. FASEB J. 28, 4710–4718 (2014). www.fasebj.org