Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage.

Brandon A Miller,Monica Chau,Gustavo Pradilla,Nefize Turan

doi:10.1155/2014/384342

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.

Highlights

Subarachnoid hemorrhage (SAH) remains a devastating disease, leaving survivors with neurological injuries that range from subtle cognitive deficits to disabling cerebral infarctions
There is no clear explanation for the heterogeneity among patients with SAH, with some recovering well and others worsening after their initial ictus
L-citrulline administration has been shown to prevent posthemorrhagic cerebral vasospasm in the transgenic Hp 2-2 model of SAH, improve neurological function as determined by PGA scores, and reverse the decrease in upregulation of inducible NOS (iNOS) and eNOS expression in Hp 2-2 animals compared with baseline levels in mice [126]

Summary

Introduction

Subarachnoid hemorrhage (SAH) remains a devastating disease, leaving survivors with neurological injuries that range from subtle cognitive deficits to disabling cerebral infarctions. While treatment continues to evolve and improve, there are few therapies that treat the underlying pathological mechanisms of SAH. There is no clear explanation for the heterogeneity among patients with SAH, with some recovering well and others worsening after their initial ictus. We will discuss the evidence supporting the role of inflammation as a direct mediator of neurological injury after SAH and a causative factor of post-SAH vasospasm. We hypothesize that the diffuse inflammatory response after SAH results in acute and chronic neurological injury and vasospasm and that patients with more severe inflammatory responses may experience worse outcomes after SAH. An improved understanding of the inflammatory pathways activated after SAH will likely lead to novel therapies and improved patient outcomes

Evidence for Acute Inflammation after Subarachnoid Hemorrhage

Evidence for Inflammation in Animal Models of SAH

The Role of Inflammation in Vasospasm after SAH

Findings

Discussion

Conclusion