Slain2 attenuates brain injury following subarachnoid hemorrhage by controlling axonal microtubule structure in mice

Neuronal injury is accountable for the poor outcome of SAH patients. In this study, oxyhemoglobin (oxyHb) was used to treat cultured primary neurons to simulate SAH, while the SAH model was established by vascular puncture in mice. First, proteomics analysis and western blot assays showed Slain2 as an increased factor in neurons exposed to oxyHb treatment, which has been reported to play an important role in axonal development by regulating microtubule stability. Upregulation of neuronal Slain2 was also detected in the murine SAH model compared with sham surgery. In addition, there was no sex difference in the protein level of Slain2 in either the sham-operated or SAH groups. Furthermore, Slain2 overexpression rescued SAH-induced sensorimotor impairments in mice, while Slain2 knockdown had the opposite effect. Finally, Slain2 overexpression rescued SAH-induced axonal injury both in vivo and in vitro, which was exacerbated by Slain2 knockdown. Thus, we demonstrate here that Slain2 acts as an endogenous protective factor of neuronal axonal microtubule structure, which plays a key role in the protection against SAH-induced neuronal axonal injury. Facilitated axonal microtubule structure by Slain2 overexpression may reduce SAH-induced axonal injury and neurobehavioral dysfunction.