Exsanguination Postconditioning of ICH (EPIC-H) Using the Lancet for Brain Bleed in Rodents, Preliminary Study

Abstract

Cerebral iron overload contributes to free-radical damage and secondary brain injury following intracerebral hemorrhage (ICH). Phlebotomy most effectively removes iron from the human body, compared with any pharmacological agent (e.g., chelator), and does not impact mean arterial blood pressure. For centuries, this ancient method was a treatment for stroke. This is the first controlled scientific evaluation of this approach after ICH. Femoral catheterization occurred at 30 min following collagenase infusion. Three different exsanguination volumes were tested: 1, 2, 3 ml (approximately 5–15 % (normotensive) loss of total blood volume; or 3.33–10 ml/kg) compared with ICH and sham controls. Brain water content, hemorrhage size, and neuroscore were measured 24 h later. Preliminary analysis of the data demonstrated that therapeutic phlebotomy occurring shortly after ICH in adult rats significantly decreased brain edema and hemorrhagic size at 1 day after the brain injury. However, the neuroscore was unchanged compared with untreated animals. Therefore, exsanguination therapy after ICH using the traditional phlebotomy approach may eventually ameliorate early brain injury (hemorrhage and edema) in further human studies, despite equivocal changes in the short-term neurological functional ability. In meantime, translational studies must further delineate the involvement of specific neuroprotective molecules, sympathetic responses, hemodynamic-vasoactive mediators, or neuroendocrine factors involved in this apparent postconditioning approach following ICH in rodents.