Crosstalk between soluble PDGF-BB and PDGFRβ promotes astrocytic activation and synaptic recovery in the hippocampus after subarachnoid hemorrhage

Platelet-derived growth factor receptor beta (PDGFR beta) dynamically changes after brain injury, possibly mediating the neuroprotective role of soluble homodimers of the platelet-derived growth factor beta subunit (PDGF-BB) that is secreted by microcirculation cells. The aim of this study was to determine whether binding of PDGF-BB to astrocytic PDGFR beta enhanced crosstalk among the various components of the neurovascular unit, leading to synaptic recovery after subarachnoid hemorrhage (SAH). The soluble PDGF-BB from the cerebrospinal fluid (CSF) of patients with SAH was measured. The relationship between PDGF-BB treatment and astrocytic PDGFR beta signaling was further explored in vivo and in vitro in experimental SAH models. Compared with the levels in the control samples, the PDGF-BB protein levels in the CSF of patients with SAH were significantly increased. After the generation of experimental SAH, astrocyte activation markers were markedly induced by the binding of PDGF-BB to astrocytic PDGFR beta, accompanied by improved levels of synaptic recovery and cognitive function. Soluble PDGF-BB and astrocytic PDGFR beta signaling are essential for the neuroprotective effect in the hippocampus and the coculture system in vitro after SAH that otherwise leads to cognitive dysfunction and neuronal damage.-Zhou, X., Wu, Q., Lu, Y., Zhang, X., Lv, S., Shao, J., Zhou, Y., Chen, J., Hou, L., Huang, C., Zhang, X. Crosstalk between soluble PDGF-BB and PDGFR beta promotes astrocytic activation and synaptic recovery in the hippocampus after subarachnoid hemorrhage.