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

Platelet-derived growth factor receptor β (PDGFRβ) dynamically changes after brain injury, possibly mediating the neuroprotective role of soluble homodimers of the platelet-derived growth factor β subunit (PDGF-BB) that is secreted by microcirculation cells. The aim of this study was to determine whether binding of PDGF-BB to astrocytic PDGFRβ 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 PDGFRβ 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 PDGFRβ, accompanied by improved levels of synaptic recovery and cognitive function. Soluble PDGF-BB and astrocytic PDGFRβ 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. [ABSTRACT FROM AUTHOR]