Research articleCD47 deficiency improves neurological outcomes of traumatic brain injury in mice

- CD47 gene knockout (KO) inhibited neutrophil infiltration into the brain at 24 h after TBI compared to wild type (WT).
- CD47 KO decreased long-term sensorimotor function deficits up to 21 days after TBI, and reduced brain lesion volume at 21 days post TBI compared to WT.
- CD47 KO increased brain vessel density at 21 days after TBI compared to WT.
- CD 47 KO up-regulated VEGF gene expression in peri-lesion cortex at 7 and 14 days after TBI compared to WT.

CD47 is a receptor for signal-regulatory protein alpha (SIRPα) in self-recognition by the innate immune system, and a receptor of thrombospondin-1 (TSP-1) contributing to vascular impairment in response to stress. However, the roles of CD47 in traumatic brain injury (TBI) have not been investigated. In this study we aimed to test our hypothesis that CD47 mediates early neutrophil brain infiltration and late brain vascular remodeling after TBI. Mice were subjected to TBI using a controlled cortical impact (CCI) device. We examined early phase neutrophil infiltration, and late phase brain vessel density, pro-angiogenic markers VEGF and Ang-1 protein expression, neurological function deficits and lesion volumes for up to three weeks after TBI. Our results show that mice deficient in CD47 (CD47 Knockout) had significantly less brain neutrophil infiltration at 24 h, upregulated VEGF expression in peri-lesion cortex at 7 and 14 days, and increased blood vessel density at 21 days after TBI, compared to wild type (WT) mice. CD47 knockout also significantly decreased sensorimotor function deficits and reduced brain lesion volume at 21 days after TBI. We conclude that CD47 may play pathological roles in brain neutrophil infiltration, progression of brain tissue damage, impairment of cerebrovascular remodeling and functional recovery after TBI.