Effects of pro-inflammatory cytokines on apolipoprotein E secretion by a human astrocytoma cell line (CCF-STTG1)

Petzold

Kerr

et al. 2003

Stroke

Background and Purpose-The apolipoprotein E (APOE) ⑀4 allele has been associated with unfavorable outcome after subarachnoid hemorrhage (SAH), suggesting that apoE plays an important role in the response of the brain to SAH. We determined the concentration of apoE in the cerebrospinal fluid (CSF) of patients with SAH and a control group to test the hypothesis that alterations in CSF apoE reflect the response of the brain to SAH and are correlated with the severity of injury and outcome. Methods-ApoE and S100B (a marker of brain injury) were measured by ELISA in CSF from a non-brain-injured control group and patients with SAH. The severity of SAH was determined from the Glasgow Coma Scale, and the clinical outcome was determined from the Glasgow Outcome Scale. Results-In contrast to increased CSF concentration of S100B, CSF apoE concentration was significantly lower in patients after SAH than in control subjects (Mann-Whitney test, PϽ0.0001). SAH patients with more severe injury and less favorable outcome had lower CSF apoE concentration than did patients with milder injury and better clinical outcome (Fisher exact test, Pϭ0.02). Conclusions-The concentration of apoE in the CSF decreases after SAH, despite the likely leakage of plasma apoE into the CSF. We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury, where, in view of previous data, it may have a protective role.

Section: Discussionmentioning

confidence: 99%

“…19 In brief, rabbit polyclonal anti-human apoE antibody (Dako) diluted in 0.02 mol/L citrate buffer was used as the capture antibody. The coated plate was washed with PBS and then blocked with 2% BSA.…”

Section: Apoe Assaymentioning

confidence: 99%

Decreased Cerebrospinal Fluid Apolipoprotein E After Subarachnoid Hemorrhage

Petzold

Kerr

et al. 2003

Stroke

“…ApoE was assayed by immunoassay as previously described (Kay et al, 2003b;Starck et al, 2000). Total tau (Innogenetics, Ghent, Belgium), Ab 1-40 and Ab 1-42 (BioSource International, Camarillo, CA) were assayed with commercial kits according to the manufacturers instructions.…”

Section: Methodsmentioning

confidence: 99%

Alterations in Cerebrospinal Fluid Apolipoprotein E and Amyloidβ-Protein after Traumatic Brain Injury

Petzold²,

Kerr³

et al. 2003

Journal of Neurotrauma

There is evidence that apolipoprotein E (apoE) and amyloid beta-protein (Abeta), which are implicated in the pathology of chronic neurodegenerative disorders, are involved in the response of the brain to acute injury; however, human in vivo evidence is sparse. We conducted a prospective observational study to determine the magnitude and time-course of alterations in cerebrospinal fluid (CSF) apoE and Abeta concentrations after traumatic brain injury (TBI), and the relationship of these changes to severity of injury and clinical outcome. Enzyme linked immunosorbant assay (ELISA) was used to assay apoE, Abeta(1-40) and Abeta(1-42) in serial CSF samples from 13 patients with TBI and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury. There was a significant decrease in CSF apoE (p < 0.001) and Abeta (p< 0.001) after TBI contrasting the observed elevation in CSF S100B (p < 0.001) and tau (p < 0.001) concentration. There was significant correlation (r = 0.67, p = 0.01) between injury severity and the decrease in Abeta(1-40) concentration after TBI. In vivo, changes in apoE and Abeta concentration occur after TBI and may be important in the response of the human brain to injury.

“…"In-house" enzyme-linked immunosorbant assays (ELISAs) were used to measure CSF S100B and apoE according to published methods (Green et al, 1997;Starck et al, 2000). In brief, for S100B, 96 well microtitre plates were coated with 200 mL of 0.05 M carbonate buffer containing monoclonal anti-S100B (Affinity Research Products, Exeter, U.K.).…”

Section: Methodsmentioning

confidence: 99%

“…In vitro studies report reduced apoE concentrations in astrocyte culture medium in response to pro-inflammatory cytokines, which are known to be elevated after TBI (Baskin et al, 1997;Starck et al, 2000).…”

mentioning

confidence: 99%

Cerebrospinal Fluid Apolipoprotein E Concentration Decreases after Traumatic Brain Injury

Petzold

Kerr

et al. 2003

Journal of Neurotrauma

The APOE epsilon4 allele has been associated with unfavorable outcome after several types of acute brain injury, yet the biological mechanisms underlying this observation are poorly understood. Postmortem and experimental brain injury studies suggest the presence of increased amounts of apolipoprotein E (apoE) within the neuropil after acute brain injury. We assayed the concentration of apolipoprotein E in the cerebrospinal fluid (CSF) of non-injured controls and patients with traumatic brain injury (TBI) to determine whether differences exist, and if these differences correlate with injury severity and clinical outcome. CSF apoE and S100B, a marker of injury severity, were measured by enzyme linked immunosorbant assay. CSF was sampled from 27 traumatic brain injury patients (mean age 32, median 25, range 16-65 years) within 3 days of injury, and 28 controls (mean age 40, median 37, range 19-73 years). The TBI patients all had a Glasgow Coma Score (GCS) of less than eight (i.e., severe head injury). Clinical outcome was determined using the Glasgow Outcome Score (GOS). The average concentration of apoE in the CSF of controls was 12.4 mg/L (95% CI: 10.5-14.3 mg/L) and in TBI patients was 3.7 mg/L (95% CI: 2.1-4.1 mg/L; Mann-Whitney: p < 0.0001). In contrast, the concentration of S100B in the CSF of TBI patients was significantly higher than that of controls (Mann-Whitney: p < 0.0001). We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury where in view of previous data, it may have a protective role.