Inflammation, Vasospasm, and Brain Injury after Subarachnoid Hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) can lead to devastating neurological outcomes, and there are few pharmacologic treatments available for treating this condition. Both animal and human studies provide evidence of inflammation being a driving force behind the pathology of SAH, leading to both direct brain injury and vasospasm, which in turn leads to ischemic brain injury. Several inflammatory mediators that are elevated after SAH have been studied in detail. While there is promising data indicating that blocking these factors might benefit patients after SAH, there has been little success in clinical trials. One of the key factors that complicates clinical trials of SAH is the variability of the initial injury and subsequent inflammatory response. It is likely that both genetic and environmental factors contribute to the variability of patients' post-SAH inflammatory response and that this confounds trials of anti-inflammatory therapies. Additionally, systemic inflammation from other conditions that affect patients with SAH could contribute to brain injury and vasospasm after SAH. Continuing work on biomarkers of inflammation after SAH may lead to development of patient-specific anti-inflammatory therapies to improve outcome after SAH.

Intraventricular Fibrinolysis with Tissue Plasminogen Activator is Associated with Transient Cerebrospinal Fluid Inflammation: A Randomized Controlled Trial

“…Inflammation has been implicated as contributing to early and delayed brain injury in patients with aneurysmal SAH, and in contributing to hydrocephalus in patients with IVH. [8][9][10]40 Accordingly, we found significantly higher baseline CSF cytokine concentrations among patients who had poor neurologic outcomes at 6 months. Still, it remains possible that more rapid clearance of blood could have a net benefit, since the ongoing presence of blood in the ventricles and subarachnoid space (probably with more gradual release of hemoglobin breakdown products) also induces inflammation that persists for several days.…”

“…37 Heme itself may be neurotoxic and may induce inflammation, before being degraded into carbon monoxide, biliverdin, and iron by the enzyme heme oxygenase, which becomes markedly upregulated in glial cells in the context of SAH. 4,6,9,38 Iron subsequently accumulates in glial cells and astrocytes, and also reacts with hydrogen peroxide to form reactive oxygen species, which in turn induces oxidative injury and exacerbates inflammation. 4,8,38 It is now well established by randomized trials that pharmacological use of intraventricular TPA accelerates hematoma clearance, both from the ventricles and basal cisterns.…”

Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats

“…Aneurysmal subarachnoid hemorrhage (SAH) is a common and severe neurological disorder, which is associated with high rates of mortality and morbidity [1]. Despite the recent progress in microsurgical and endovascular surgical techniques, the outcome of patients who suffer a SAH remains unsatisfactory [2].…”

Corticosteroids in the Management of Hyponatremia, Hypovolemia, and Vasospasm in Subarachnoid Hemorrhage: A Meta-Analysis

“…It is hypothesized that vasospasm is related to the inflammatory response after SAH [35,36] ; SVS events/total n: corticosteroid = 61/211, control = 137/392). However, in three of these studies [14,15,23] , both control and treatment groups received nimodipine, and in 2 studies [14,15] , the control groups also received a 'low' amount of steroids.…”