Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage–induced secondary brain injury and as potential targets for intervention

Abstract

<jats:p>Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, <jats:italic>N</jats:italic>-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.</jats:p>

Naringin Reverses Neurobehavioral and Biochemical Alterations in Intracerebroventricular Collagenase-Induced Intracerebral Hemorrhage in Rats

“…Divalent iron ions, inflammatory cells such as microglia and neutrophils interact with lipid and generate free radicals. Activated neutrophils also interact with respiratory chain, and result in the release of a large amount of reactive oxygen species, nitric oxide and a decrease in superoxide dismutase (SOD) due to its excessive consumption [10,11,12,13]. Furthermore, as human brain is rich in mitochondria and unsaturated fats such as myelin, it is vulnerable to free radical damage and lipid peroxidation.…”

Effects of thrombin on the secondary cerebral injury of perihematomal tissues of rats after intracerebral hemorrhage

“…Thrombin-mediated overactivation of microglia and leukocytes can cause pathological damage to the central nervous system, and it is a potential therapeutic target for reducing tissue damage (Hu et al, 2011;Babu et al, 2012). Hirudin is a known, potent, specific, and exogenous inhibitor of thrombin.…”

Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage

“…Previous MRI investigations and animal experiments supported a vasogenic origin of PHE in ICH rather than cytotoxicity or ischemia [37][38][39][40]. Due to the fact that hematoma evacuation was not performed in either group, an additional mechanism must be responsible for the difference in edema formation [41]. The difference in PHE formation might be due to the DC itself.…”