Septic Encephalopathy: Relationship to Serum and Cerebrospinal Fluid Levels of Adhesion Molecules, Lipid Peroxides and S-100B Protein

Abstract

Severe septic illness is often associated with cerebral manifestations such was disturbed consciousness and delirium. Little was known about its effect on the CNS. This is the first study in children that has assessed the direct mediators of brain inflammation and injury with sepsis. The serum and CSF concentrations of soluble intracellular adhesion molecule-1 (sICAM-1) (marker of endothelium-leukocyte interaction), nitric oxide (NO) and lipid peroxide (LPO) (markers for lipid peroxidation) and S-100B protein (marker of astrocytes activation and injury), were measured in 40 children with sepsis of whom 40% had moderate to severe septic encephalopathy. Serum from 25 normal children was used for comparison. Serum values of sICAM-1, NO, LPO and S100B were elevated in patients compared to controls. The greater elevation of the CSF:serum albumin ratio suggests loss of blood-brain barrier integrity. After normalising for CSF:serum albumin ratio, we demonstrated a significant intrathecal synthesis of NO, LPO and S100B. Patients with encephalopathy had elevated serum and CSF levels of sICAM-1, NO, LPO and S100B compared to sepsis only. This study indicates that the brain is vulnerable in children with sepsis. It also suggests that coordinated interactions between immune system, vascular endothelial cells, CNS barriers, astrocytes and brain lipid peroxides, may contribute to septic encephalopathy.

Sepsis-induced alterations in sleep of rats

“…These epidemiologic data demonstrate that sepsis must also be viewed as a long-term chronic condition and that severe sepsis remains a tremendous public health burden in terms of lives lost and cost. However, although sepsis is often associated with cognitive impairment and end-stage encephalopathy [e.g., (20)], relatively little research has focused on the impact of sepsis on central nervous system (CNS) processes.…”

In Vivo Imaging of Septic Encephalopathy

“…MicroRNA (i.e., noncoding small RNA) involved in RNA silencing and posttranscriptional modification [76]. Besides nitric oxide (NO), lipid peroxidase, S100B protein [77], and the prion protein [78] may participate in SE.…”

“…Finally, in addition to our challenges, other candidate biomarkers which employ correlation to the pathological state of SE are recently addressed: S100β (i.e., astrocyte-secreting protein) [77,[118][119][120], free radicals [121,122], ascorbate [123][124][125], and various neuropeptides [126]. In addition, adult neurogenesis was induced in a rat model of SE and the neurogenesis marker (e.g., 5-bromo-2′-deoxyuridine) might be useful [127].…”

Diagnostic Value of S100B Protein in Critical Conditions

“…Выявлена положительная корреляция между кон центрацией S100B в СМЖ и активацией перекисного окисле ния липидов, а также между соотношением S100B и степенью тяжести течения менингита [48]. Обнаружена положительная корреляция между сывороточным S100B с общим содержани ем тиолов в сыворотке, что предположительно указывает на то, что повреждение астроцитов может увеличивать образование S100B в соответствии с тяжестью окислительного стресса [49,50]. Точные механизмы, отвечающие за увеличение интрате кального уровня S100B белка при бактериальных менингитах неизвестны.…”