When the Blood Hits Your Brain: The Neurotoxicity of Extravasated Blood

Abstract

Hemorrhage in the central nervous system (CNS), including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and aneurysmal subarachnoid hemorrhage (aSAH), remains highly morbid. Trials of medical management for these conditions over recent decades have been largely unsuccessful in improving outcome and reducing mortality. Beyond its role in creating mass effect, the presence of extravasated blood in patients with CNS hemorrhage is generally overlooked. Since trials of surgical intervention to remove CNS hemorrhage have been generally unsuccessful, the potent neurotoxicity of blood is generally viewed as a basic scientific curiosity rather than a clinically meaningful factor. In this review, we evaluate the direct role of blood as a neurotoxin and its subsequent clinical relevance. We first describe the molecular mechanisms of blood neurotoxicity. We then evaluate the clinical literature that directly relates to the evacuation of CNS hemorrhage. We posit that the efficacy of clot removal is a critical factor in outcome following surgical intervention. Future interventions for CNS hemorrhage should be guided by the principle that blood is exquisitely toxic to the brain.

Operative management of intracerebral hemorrhage: 3 year experience in multidisciplinary city hospital

“…The mechanisms responsible for brain damage within a cerebral hematoma are numerous and complex: initially, there is a direct effect of acute bleeding into the brain parenchyma, causing a mass effect, which is subsequently accompanied by hemorrhage arrest in about two-thirds of patients. However, in the remaining third of patients, the hematoma continues to grow during the first 24 hours, which contributes to an additional mass effect, midline shift and leads to further neurological deficit and an increased risk of adverse outcomes [8][9][10].…”

Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage

“…Oxyhemoglobin and its metabolites are considered to be the main sources of reactive oxygen species (ROS) in the pathophysiological process of SAH (Hugelshofer et al, 2018). After hemolysis, tetrameric hemoglobin is released from RBCs and degrades gradually, producing toxic intermediates (Stokum et al, 2021). Among them, heme is considered more toxic than hemoglobin (Bulters et al, 2018).…”

Network pharmacological analysis of active components of Tongqiao Huoxue Decoction in the treatment of intracerebral hemorrhage

“…However, the neuroinflammatory cascade triggered by the immune response after ICH further aggravates neurological damage. It has been demonstrated that pathophysiological changes in the NVU and glial network after ICH provide therapeutic targets for ameliorating ICH-induced secondary brain injury (6)(7)(8).…”