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.