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.

Figure 1

Schematic of a coronal projection of a ruptured cerebral aneurysm and contributing factors that result in cerebral vasospasm after SAH and delayed ischemic injury. Many inflammatory factors are hypothesized to contribute to brain injury and vasospasm after SAH. The interface between subarachnoid blood, brain parenchyma, and the cerebral vasculature is the likely location for induction of inflammatory cascades that lead to brain injury and vasospasm after SAH.