Holo-transferrin and thrombin can interact to cause brain damage.

BACKGROUND AND PURPOSE Previous studies have suggested that delayed release of hemoglobin degradation products, particularly iron, is involved in intracerebral hemorrhage (ICH)-induced brain injury. However, a recent study found evidence of iron-induced brain injury soon after ICH. This study, therefore, examined whether another iron-containing component of blood, holo-transferrin (holo-Tf), might also induce brain injury either alone or in combination with thrombin, another factor involved in early ICH-induced brain injury. METHODS Male Sprague-Dawley rats received an intracerebral infusion of holo-Tf, apo (noniron-loaded)-Tf, thrombin, or a combination of Tf with thrombin into the right basal ganglia. The rats were euthanized 24 hours later for measurement of brain edema and assessment of DNA damage (single- and double-strand breaks and 8-hydroxyl-2'-deoxyguanosine immunohistochemistry). Iron distribution was examined histochemically. RESULTS Holo-Tf, apo-Tf, and the dose of thrombin used (1 U) all failed to induce brain edema when administered alone. However, the combination of holo-Tf with thrombin (but not apo-Tf with thrombin) caused brain edema, DNA damage, and intracellular iron accumulation in the ipsilateral basal ganglia. CONCLUSIONS These results suggest that in addition to hemoglobin-bound iron, Tf-bound iron may contribute to ICH-induced brain injury and that thrombin may contribute to the latter by facilitating cellular iron uptake.