title: Injection of neural progenitor cells attenuates decrease in level of connexin 43 in brain capillaries after cerebral ischemia.
abstract: Although functional disruption of the cerebrovasculature, which is called the "neurovascular unit (NVU)", may lead to amplification of ischemia-induced injury, changes in the gap junctional proteins within the NVU and their pathophysiological roles after brain injury remain controversial. We previously demonstrated that the intravenous injection of neural progenitor cells (NPCs) have therapeutic potential for improving the spatial learning dysfunction and depression-like behaviors observed after cerebral ischemia. In this study, we investigated whether severe cerebral ischemia would alter the expression of gap junctional proteins in isolated brain capillaries and examined the effect of intravenous injection of NPCs on the levels of these proteins. Cerebral ischemia induced a sustained decrease in the level of the gap junctional protein connexin 43 (Cx43) in the isolated brain capillaries, whereas the level of aquaporin 4 (AQP-4) was transiently increased. The injection of NPCs increased the level of Cx43 compared that of vehicle in the microsphere embolism (ME) rats, suggesting this decrease to be a possible mechanism for disruption of the astrocyte-endothelial cell interface within the NVU without causing any changes in the level of AQP-4 and N-cadherin. We also demonstrated that some of the intravenously injected NPCs migrated into the blood vessels in the peri-infarct area. These results suggest that the intravenous injection of the NPCs would remodel the NVU after severe cerebral ischemia, which remodeling might be associated with functional improvement following the NPC injection.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Moriyama
authors.forename: Norio
authors.initials: N
authors.lastname: Takagi
authors.forename: Chisa
authors.initials: C
authors.lastname: Itokawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015820:Cadherins / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D058953:Neural Stem Cells / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar
chemical_list: D051401:Aquaporin 4; D015820:Cadherins; D018031:Connexin 43