| First Author | Nirwane A | Year | 2019 |
| Journal | Acta Neuropathol Commun | Volume | 7 |
| Issue | 1 | Pages | 23 |
| PubMed ID | 30777135 | Mgi Jnum | J:295258 |
| Mgi Id | MGI:6453706 | Doi | 10.1186/s40478-019-0676-8 |
| Citation | Nirwane A, et al. (2019) Mural cell-derived laminin-alpha5 plays a detrimental role in ischemic stroke. Acta Neuropathol Commun 7(1):23 |
| abstractText | At the blood-brain barrier (BBB), laminin-alpha5 is predominantly synthesized by endothelial cells and mural cells. Endothelial laminin-alpha5 is dispensable for BBB maintenance under homeostatic conditions but inhibits inflammatory cell extravasation in pathological conditions. Whether mural cell-derived laminin-alpha5 is involved in vascular integrity regulation, however, remains unknown. To answer this question, we generated transgenic mice with laminin-alpha5 deficiency in mural cells (alpha5-PKO). Under homeostatic conditions, no defects in BBB integrity and cerebral blood flow (CBF) were observed in alpha5-PKO mice, suggesting that mural cell-derived laminin-alpha5 is dispensable for BBB maintenance and CBF regulation under homeostatic conditions. After ischemia-reperfusion (MCAO) injury, however, alpha5-PKO mice displayed less severe neuronal injury, including reduced infarct volume, decreased neuronal death, and improved neurological function. In addition, alpha5-PKO mice also showed attenuated vascular damage (milder BBB disruption, reduced inflammatory cell infiltration, decreased brain edema, and diminished hemorrhagic transformation). Mechanistic studies revealed less severe tight junction protein (TJP) loss and pericyte coverage reduction in alpha5-PKO mice after ischemia-reperfusion injury, indicating that the attenuated ischemic injury in alpha5-PKO mice is possibly due to less severe vascular damage. These findings suggest that mural cell-derived laminin-alpha5 plays a detrimental role in ischemic stroke and that inhibiting its signaling may have a neuroprotective effect. |
