Chloroquine Protects Hypoxia/Ischemia-Induced Neonatal Brain Injury in Rats by Mitigating Blood–Brain Barrier Disruption

Neonatal hypoxic-ischemic (H/I) brain damage (HIBD) is a devastating condition for which there are presently no effective therapeutic strategies against its severe neurological deficits in neonates and young children. Traditionally, H/I induces the compromise of the blood–brain barrier (BBB), which causes neuronal cell death, eventually resulting in brain secondary injury. In addition to neonatal HIBD, chloroquine (CQ) has been proved to exert a protective effect on BBB disruption in several brain injury models. The main purpose of this research was to study whether CQ protects the BBB from H/I insult and confers beneficial neuroprotection in the neonatal Rice–Vannucci rat model. Herein, we reported that CQ administration significantly reduced brain damage and improved behavioral dysplasia after H/I injury. Moreover, we demonstrated the protective effects of CQ on BBB integrity, evidenced by ameliorating brain edema and Evans blue extravasation, inhibiting the degeneration of the tight junction and adherens junction proteins, and improving pericyte survival in neonatal rats after HIBD. These findings indicated that CQ administration protected the BBB against H/I injury, thereby ameliorating brain damage and promoting neurofunctional recovery. Collectively, our data demonstrated that CQ played a crucial role in BBB integrity after neonatal H/I injury, which sheds light on the development of therapeutic agents to treat HIBD.