Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes.

Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

Decreased numbers of circulating endothelial progenitor cells are associated with hyperglycemia in patients with traumatic brain injury.

Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function. However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury, and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels (r = -0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China (approval No. 200501) in January 2015.