Early Brain Injury After Subarachnoid Hemorrhage: Incidence and Mechanisms

Abstract

Aneurysmal subarachnoid hemorrhage is a devastating condition causing significant morbidity and mortality. While outcomes from subarachnoid hemorrhage have improved in recent years, there continues to be significant interest in identifying therapeutic targets for this disease. In particular, there has been a shift in emphasis toward secondary brain injury that develops in the first 72 hours after subarachnoid hemorrhage. This time period of interest is referred to as the early brain injury period and comprises processes including microcirculatory dysfunction, blood-brain-barrier breakdown, neuroinflammation, cerebral edema, oxidative cascades, and neuronal death. Advances in our understanding of the mechanisms defining the early brain injury period have been accompanied by improved imaging and nonimaging biomarkers for identifying early brain injury, leading to the recognition of an elevated clinical incidence of early brain injury compared with prior estimates. With the frequency, impact, and mechanisms of early brain injury better defined, there is a need to review the literature in this area to guide preclinical and clinical study.

Morphometric Study of the Initial Ventricular Indices to Predict the Complications and Outcome of Aneurysmal Subarachnoid Hemorrhage

“…There are data from small cohort studies that show the positive clinical effect of glucocorticoid treatment in SAH patients [ 32 , 33 , 34 ]. This effect might show up in the early phase of SAH by the suppression of microenvironmental and systemic cytokine releases involved in different pathways of an early brain injury [ 35 , 36 ]. Moreover, the increased downregulation of inflammatory cytokines by continuous dexamethasone administration can also contribute to the prevention of secondary SAH complications such as DCI.…”

Neuroradiological diagnosis and therapy of cerebral vasospasm after subarachnoid hemorrhage

“…After an aneurysmal subarachnoid hemorrhage (SAH), brain damage can occur for various, partly unrelated reasons. The initial bleeding trauma (early brain injury [EBI]) can result primarily in an increase in intracranial pressure with possibly fatal effects on cerebral perfusion pressure [1][2][3]. A secondary damage phase begins approximately on the third day after an SAH.…”

“…Nach einer aneurysmatischen Subarachnoidalblutung (SAB) können Hirnschädigungen aus verschiedenen, teils unverbundenen Ursachen entstehen. Das initiale Blutungstrauma (Early brain injury [EBI]) kann vor allem zu einem Anstieg des intrakraniellen Drucks mit auch möglichen fatalen Einwirkungen auf den zerebralen Perfusionsdruck führen [1][2][3]. Verzögert ab etwa Tag 3 nach SAB tritt eine sekundäre Schädigungsphase auf.…”

Conditioning-based therapeutics for aneurysmal subarachnoid hemorrhage – A critical review

“…The pathophysiological drivers of secondary brain injury after SAH are commonly divided between those leading to early brain injury (EBI) versus those contributing to delayed cerebral ischemia (DCI), although these mechanisms are not mutually exclusive (Figure 1). 5 –15 EBI refers to secondary brain injury occurring within the first three days after SAH, 6 –9 with BBB breakdown, cerebral edema, neuroinflammation, increased intracranial pressure, and neuronal cell death identified as key contributors to this form of secondary brain injury. 6 –9,13 –15 DCI is a phenomenon in which new neurological deficits develop well after ictus, typically 4–12 days, with a peak incidence of 7–10 days post-SAH.…”

“…5 –15 EBI refers to secondary brain injury occurring within the first three days after SAH, 6 –9 with BBB breakdown, cerebral edema, neuroinflammation, increased intracranial pressure, and neuronal cell death identified as key contributors to this form of secondary brain injury. 6 –9,13 –15 DCI is a phenomenon in which new neurological deficits develop well after ictus, typically 4–12 days, with a peak incidence of 7–10 days post-SAH. 9 –15 Cerebral vasospasm was once thought to be the sole contributor to, and was used synonymously with, DCI; however, recent evidence implicates that microvascular autoregulatory dysfunction, 16,17 microthrombosis, 18,19 and cortical spreading depression 20 –22 also play significant pathophysiological roles.…”