Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage

Abstract

We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 AE 19 years) with Fisher's grade ! III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR ¼ 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ! III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

White matter T2 hyperintensities and blood‐brain barrier disruption in the hyperacute stage of subarachnoid hemorrhage in male mice: The role of lipocalin‐2

“…Li et al recently examined BBB leakage and brain endothelial tight junction protein changes in a similar endovascular perforation model of SAH but in rat. They found evidence of a biphasic BBB disruption with an early opening as early as 30 minutes that peaks at 3 hours and a later disruption that peaks at 72 hours post‐SAH.…”

“…after SAH, the exact mechanisms have not been fully elucidated. [5][6][7] Studies examining very early changes (hyperacute) may help elucidate the relationship between different forms of injury. For example, ultra-early BBB disruption was recently reported in cerebral ischemia and specifically targeting that endothelial injury could block later brain injury and long-term behavioral deficits.…”

Elevated Systemic IL-10 Levels Indicate Immunodepression Leading to Nosocomial Infections after Aneurysmal Subarachnoid Hemorrhage (SAH) in Patients

“…Interleukin (IL)-10 has been shown to be the master regulator of immunity, infection and immunodepression [10,11]. IL-10 is secreted by almost all types of immune cells under different conditions and is co-induced with proinflammatory cytokines via pathways that have negative regulatory feedback loops, in order to limit damage to the host [12]. For example, IL-10 inhibits the production of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-12, IL-18, G-CSF, TNF-α, PAF and LIF, as well as chemokines such as MCP-1, MCP-5, MIP-1α, MIP-1β, RANTES, CXCL8, IP-10, MIP-2 and KC [12,13].…”

The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats

“…In one study, the plasma HMGB1 in patients with SAH upon admission was significantly higher than that in healthy controls and the levels of HMGB1 were associated with long-term poor neurological outcomes [10]. In experimental SAH, cytosolic HMGB1 has been significantly increased in neurons and microglia in rats, contributing to the induction of neuroinflammation and brain injury following SAH [11,12]. An increase in the expression of HMGB1 and its receptor TLR4 in the basilar artery after SAH has been recently demonstrated [13,14].…”