Macrophage depletion alters the blood-nerve barrier without affecting Schwann cell function after neural injury

Previous work has shown that, during the early phases of chronic nerve compression (CNC) injury, axonal pathology is absent while Schwann cells undergo a dramatic process of cellular turnover with marked proliferation. It is known that macrophages may release Schwann cell mitogens, so we sought to explore the role of macrophages in CNC injury by selectively depleting the population of hematogenously derived macrophages in nerves undergoing CNC injury by injecting clodronate liposomes at days 1, 3, and 6 postinjury and evaluating both the integrity of the blood-nerve barrier (BNB) and Schwann cell function. Integrity of the BNB was evaluated by intravenously injecting Evans blue albumin (EBA), and Schwann cell number was determined via stereologic techniques. The BNB was clearly altered by 2 weeks postinjury and continued to disintegrate at later time points. Macrophage depletion attenuated this response at all observed time points. Quantification of Schwann cell nuclei in CNC nerves showed no differences between compressed sections of macrophage-depleted and nondepleted animals. Although macrophages are largely responsible for the increased vascular permeability associated with CNC injury, it is likely that the Schwann cell response to CNC injury is not influenced by macrophage-derived mitogenic signals but rather must be mediated via alternative mechanisms.