Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

Abstract

Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are identified. In addition, it is found that many of these mechanisms evolve with time and participate in the pathogenesis of delayed ischemic injury and poor outcome. Therefore, a therapy or therapies focused on these early mechanisms may not only prevent the early brain injury but may also help reduce the intensity of later developing neurological complications. This manuscript reviews the pathological mechanisms of early brain injury after SAH and summarizes the status of current therapies.

Attenuation of neurological injury with early baicalein treatment following subarachnoid hemorrhage in rats

“…The results of our study were in line with those of previous reports as early brain injury treatment after SAH can attenuate some of the devastating secondary injuries from SAH such as vasospasm. 2,21,27 It has long been known that glutamate is detrimental to neurons following SAH. 9,16,34 In an in vitro study, baicalein has been demonstrated to have a protective effect against glutamate-induced neurotoxicity.…”

“…27 Therefore, therapies focused on these early processes may prevent not only early brain injury but also reduce the development of the subsequent neurological sequelae.…”

Early Systemic Procalcitonin Levels in Patients with Aneurysmal Subarachnoid Hemorrhage

“…ROC curve analysis of the two studies revealed an AUC of 0.98 and 0.94, respectively [5,6]. The rupture of an intracranial aneurysm is associated with a sudden ICP increase and may reach values as high as 162 mmHg [3,21,22]. The sharp increase of ICP leads to a decrease of the cerebral perfusion pressure (CPP) with a consequent critical decrease of the cerebral blood flow (CBF) [22][23][24].…”

“…This might be explained as follows: Early brain injury after aSAH cannot be (over-) simplified to transient global cerebral hypoxia due to CBF decrease or arrest. There are several patho-physiological mechanisms that activate within minutes after the initial bleeding such as mechanical and bio-chemical trauma caused by the hematoma itself [3]. Furthermore, it is well known that patients with aSAH are specifically at risk of secondary neurological injury, which may be caused by 1) CVSdependent or -independent delayed ischemic events, aka DCI, 2) ''collateral damage'' in conjunction with the aneurysm securement, and/or 3) rebleeding [1,27].…”

“…More recently, mechanisms of early brain injury have moved center stage in the research focus. It has been suggested that these mechanisms evolve with time and contribute to the path-ogenesis of DCI [3,4]. The rupture of an aneurysm and consequent release of blood into the subarachnoid space leads to an abrupt increase of the intracranial pressure (ICP), which is suggested to cause a brief cerebral perfu-sion arrest [4].…”