Dexamethasone impairs neurofunctional recovery in rats following traumatic brain injury by reducing circulating endothelial progenitor cells and angiogenesis.

The administration of glucocorticoids (GCs) after traumatic brain injury (TBI) is controversial. Clinical evidence reveals the deleterious effects of GCs, but the mechanism remains unclear. Previous studies indicate that GCs impair wound healing by affecting endothelial progenitor cell (EPC) function and inhibiting angiogenesis after skin injury. Thus, we hypothesize that the central deleterious effect of GCs is associated with reduced EPCs and angiogenesis after TBI. Using a controlled cortical impact model, we examined the dynamic changes in circulating EPCs and in the regional microcirculation within 14 days of TBI by flow cytometry analysis and contrast-enhanced ultrasound, respectively. The modified neurological severity score (mNSS) and Morris water maze assay were used to assess neurological recovery. Angiogenesis and hippocampal neuron counts were assessed using immunohistochemistry analysis and hematoxylin and eosin staining 14 days after TBI. Compared with the TBI control group, dexamethasone treatment significantly reduced the number of circulating EPCs on days 1, 3, 7 and 14 (P < 0.05); decreased the number of CD31+ cells, the peak intensity and the number of hippocampal neurons on day 14 (P < 0.05); increased the latency on days 12 and 13 (P < 0.05); and reduced the percentage of time spent in the goal quadrant (P < 0.05) on day 14. Similarly, dexamethasone increased the mNSS on days 7 and 14 (P < 0.05). A strong correlation was observed between these results at 14 days after TBI (r = 0.815-0.892, P < 0.05). These data indicate that DEX inhibits the mobilization of EPC levels and angiogenesis around the lesion after TBI, which may contribute to neuronal cell loss and impaired neurofunction.