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.