Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury

Pilitsis, Julie G.; Coplin, William M.; O’Regan, Michael H.; Wellwood, Jody; Díaz, Fernando G.; Fairfax, Marilynn R.; Michael, Daniel B.; Phillis, John W.

doi:10.1016/s0304-3940(03)00803-6

Cited by 78 publications

(60 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in studies of Alzheimer (33) and Parkinson (34) diseases, neither free nor acyl-carnitine levels significantly correlate with disease. Free fatty acids were shown to increase in patients with traumatic brain injury (35), stroke (36), and subarachnoid hemorrhage (37), yet a decrease in fatty acid concentrations was demonstrated in multiple sclerosis (38) and Alzheimer disease (39).…”

Section: Discussionmentioning

confidence: 99%

“…Sections 6 μm long were cut from the paraffin blocks, mounted on glass slides, and either subjected to hematoxylin and eosin staining (Sigma-Aldrich), in situ hybridization analysis, or immunohistochemical staining. In situ hybridization analysis was performed as previously described (65) using 35 S-labeled single-strand RNA probes consisting of fragments of the rhesus monkey PLA1A or PLA2G4C, obtained by RT-PCR amplification using oligonucleotides derived from the homologous GenBank sequences, cloned into a vector with opposable RNA bacteriophage promoters, and sequence verified. In addition to the antisense probe hybridization, controls included sense probe hybridization.…”

Section: Monkeys and Siv Rhesus Monkeys Were Intravenously Inoculatementioning

confidence: 99%

See 1 more Smart Citation

Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques

Wikoff¹,

Pendyala²,

Siuzdak³

et al. 2008

J. Clin. Invest.

127

113

View full text Add to dashboard Cite

HIV infiltrates the CNS soon after an individual has become infected with the virus, and can cause dementia and encephalitis in late-stage disease. Here, a global metabolomics approach was used to find and identify metabolites differentially regulated in the cerebrospinal fluid (CSF) of rhesus macaques with SIV-induced CNS disease, as we hypothesized that this might provide biomarkers of virus-induced CNS damage. The screening platform used a non-targeted, mass-based metabolomics approach beginning with capillary reverse phase chromatography and electrospray ionization with accurate mass determination, followed by novel, nonlinear data alignment and online database screening to identify metabolites. CSF was compared before and after viral infection. Significant changes in the metabolome specific to SIV-induced encephalitis were observed. Metabolites that were increased during infection-induced encephalitis included carnitine, acyl-carnitines, fatty acids, and phospholipid molecules. The elevation in free fatty acids and lysophospholipids correlated with increased expression of specific phospholipases in the brains of animals with encephalitis. One of these, a phospholipase A2 isoenzyme, is capable of releasing a number of the fatty acids identified. It was expressed in different areas of the brain in conjunction with glial activation, rather than linked to regions of SIV infection and inflammation, indicating widespread alterations in infected brains. The identification of specific metabolites as well as mechanisms of their increase illustrates the potential of mass-based metabolomics to address problems in CNS biochemistry and neurovirology, as well as neurodegenerative diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Monkeys and Siv Rhesus Monkeys Were Intravenously Inoculatementioning

confidence: 99%

Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques

Wikoff¹,

Pendyala²,

Siuzdak³

et al. 2008

J. Clin. Invest.

127

113

View full text Add to dashboard Cite

show abstract

“…For PC, the mean ratio of DHA-to AA-containing species was significantly affected by the injury (F (1,36) ϭ18.1, PϽ0.001), and there was an interaction between the brain regions and injury (F (2,30) ϭ20.1, PϽ0.001). Post hoc analyses showed a decrease in the mean ratio of DHA-to AA-containing PC species within the hippocampi and cortices of injured compared to control mice (PϽ0.05; Fig.…”

Section: Ratios Of Dha-to Aa-containing Pc Pe and Pi Species Acrossmentioning

confidence: 99%

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

et al. 2014

View full text Add to dashboard Cite

Phospholipid (PL) abnormalities are observed in the cerebrospinal fluid of patients with traumatic brain injury (TBI), suggesting their role in TBI pathology. Therefore, PL levels were examined in a TBI mouse model that received 1.8 mm deep controlled cortical impact injury or craniectomy only (control). The rotarod and Barnes maze acquisition and probe tests were performed within 2 wk after injury, with another probe test performed 3 mo postinjury. Liquid chromatography/mass spectrometry analyses were performed on lipid extracts from several brain regions and plasma from injured and control mice collected at 3 mo postinjury. Compared to controls, injured mice with sensorimotor and learning deficits had decreased levels of cortical and cerebellar phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels, while hippocampal PC, sphingomyelin and PE levels were elevated. Ether PE levels were lower in the cortices and plasma of injured animals. Polyunsaturated fatty acid-containing PC and PE species, particularly ratios of docosahexaenoic acid (DHA) to arachidonic acid, were lower in the hippocampi and cortices and plasma of injured mice. Given the importance of DHA in maintaining neuronal function and resolving inflammation and of peroxisomes in synthesis of ether PLs, normalizing these PLs may be a useful strategy for treating the chronic pathology of TBI.-Abdullah, L., Evans, J. E., Ferguson, S., Mouzon, B., Montague, H., Reed, J., Crynen, G., Emmerich, T., Crocker, M., Pelot, R., Mullan, M., Crawford, F. Lipidomic analyses identify injury-specific phospholipid changes 3 months after traumatic brain injury. FASEB J. 28, 5311-5321 (2014). www.fasebj.org Key Words: controlled cortical impact ⅐ mass spectrometry ⅐ phosphatidylcholine ⅐ phosphatidylethanolamine ⅐ phosphatidylinositol ⅐ sphingomyelin Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States among adults from both the civilian and military populations. Due to the improvements made in military body armor and combat helmets over the past 2 decades, the rate of severe TBI associated with Iraq and Afghanistan deployments has decreased to 1% of the total TBI sustained by military personnel, a rate that is lower than those reported for previous deployments (1-3). Estimates from the U.S. Centers for Disease Control and Prevention suggest that severe TBI remains an important issue in the civilian population. In 2010, 2.5 million admissions to emergency departments were due to TBI (4) contributing to about a third of injury related deaths in the United States. The annual U.S. costs associated with TBI are estimated to be $75 billion, largely attributed to medical care, loss of productivity, and long-term disability (5). Although mild TBI occurs more frequently than severe TBI, the latter has the largest adverse effect on the activities of daily living of injured individuals and accounts for 90% of the total TBI-related medical costs (5). The primary injury is caused by the immediate force of the trauma a...

show abstract

“…Further supporting reports demonstrated that in traumatic brain injury, free fatty acid (FFA) levels increase significantly in the cerebrospinal fluid (CSF), and are recognized as markers of brain injury. In particular, the concentration of palmitate almost doubled as compared to control, above 1100 g/L in the CSF of traumatic brain injury versus around 600 g/L in control (Pilitsis et al, 2003;Pilitsis et al, 2001;Zamir et al, 1991). FFAs in plasma can cross the blood-brain barrier (Dhopeshwarkar and Mead, 1973;Smith and Nagura, 2001), and high fat diets increase the uptake of fatty acids by the brain from the plasma (Karmi et al, 2010;Wang et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

P3–076: Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes

Liu

Martin

Kohler

et al. 2013

Alzheimer's & Dementia

View full text Add to dashboard Cite

Deregulation of calcium has been implicated in neurodegenerative diseases, including Alzheimer's disease (AD). Previously, we showed that saturated free-fatty acid, palmitate, causes AD-like changes in primary cortical neurons mediated by astrocytes. However, the molecular mechanisms by which conditioned media from astrocytes cultured in palmitate induces AD-like changes in neurons are unknown. This study demonstrates that this condition media from astrocytes elevates calcium level in the neurons, which subsequently increases calpain activity, a calcium-dependent protease, leading to enhance p25/Cdk5 activity and phosphorylation and activation of the STAT3 (signal transducer and activator of transcription) transcription factor. Inhibiting calpain or Cdk5 significantly reduces the upregulation in nuclear level of pSTAT3, which we found to transcriptionally regulate both BACE1 and presenilin-1, the latter is a catalytic subunit ofsecretase. Decreasing pSTAT3 levels reduced the mRNA levels of both BACE1 and presenilin-1 to near control levels. These data demonstrate a signal pathway leading to the activation of STAT3, and the generation of the amyloid peptide. Thus, our results suggest that STAT3 is an important potential therapeutic target of AD pathogenesis.

show abstract

Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury

Cited by 78 publications

References 11 publications

Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques

Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

P3–076: Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes

Contact Info

Product

Resources

About