Remodeling of cerebrospinal fluid lipoprotein particles after human traumatic brain injury

Andrew D. Kay, Stephen P. Day, Mary Kerr, James A.R. Nicoll, Chris J. Packard, Muriel J. Caslake

Research output: Contribution to journalArticle

Abstract

The association between possession of the APOE epsilon4 allele and unfavourable outcome after traumatic brain injury (TBI) suggests that the apolipoprotein E protein (apoE) plays a key role in the response of the human brain to injury. ApoE is known to regulate cholesterol metabolism in the periphery through its action as a ligand for receptor mediated uptake of lipoprotein particles (Lps). Greater understanding of cholesterol metabolism in the human central nervous system may identify novel treatment strategies applicable to acute brain injury. We report findings from the analysis of lipoproteins in the cerebrospinal fluid (CSF) of patients with TBI and non-injured controls, testing the hypothesis that remodeling of CSF lipoproteins reflects the response of the brain to TBI. CSF Lps were isolated from the CSF of controls and patients with severe TBI by size exclusion chromatography, and the lipoprotein fractions analysed for cholesterol, phospholipid, apoAI, and apoE. There was a marked decrease in apoE containing Lps in the TBI CSF compared to controls (p=0.002). After TBI there was no significant decrease in apoAI containing CSF Lps (CSF LpAI), but the apoAI resided on smaller sized particles than in control CSF. There was a population of very small sized Lps in TBI CSF, which were associated with the increased cholesterol (p=0.0001) and phospholipid (p=0.040) seen after TBI. The dramatic loss of apoE containing Lps from the CSF, and the substantial increase in CSF cholesterol, support the concept that apoE and cholesterol metabolism are intimately linked in the context of acute brain injury. Treatment strategies targeting CNS lipid transport, required for neuronal sprouting and synaptogenesis, may be applicable to traumatic brain injury.

Original languageEnglish
Pages (from-to)717-23
Number of pages7
JournalJournal of Neurotrauma
Volume20
Issue number8
DOIs
Publication statusPublished - 8 Jul 2003
Externally publishedYes

Fingerprint

Lipoproteins
Cerebrospinal Fluid
Apolipoproteins E
Cholesterol
Brain Injuries
Proteins
Phospholipids
Traumatic Brain Injury
Gel Chromatography
Central Nervous System
Alleles
Ligands
Lipids
Brain
Therapeutics

Keywords

  • Adolescent
  • Adult
  • Apolipoprotein A-I
  • Apolipoproteins E
  • Brain Injuries
  • Cholesterol
  • Chromatography, Gel
  • Humans
  • Lipoproteins
  • Middle Aged
  • Phospholipids
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Kay, Andrew D. ; Day, Stephen P. ; Kerr, Mary ; Nicoll, James A.R. ; Packard, Chris J. ; Caslake, Muriel J. / Remodeling of cerebrospinal fluid lipoprotein particles after human traumatic brain injury. In: Journal of Neurotrauma. 2003 ; Vol. 20, No. 8. pp. 717-23.
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Remodeling of cerebrospinal fluid lipoprotein particles after human traumatic brain injury. / Kay, Andrew D.; Day, Stephen P.; Kerr, Mary; Nicoll, James A.R.; Packard, Chris J.; Caslake, Muriel J.

In: Journal of Neurotrauma, Vol. 20, No. 8, 08.07.2003, p. 717-23.

Research output: Contribution to journalArticle

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AU - Kay, Andrew D.

AU - Day, Stephen P.

AU - Kerr, Mary

AU - Nicoll, James A.R.

AU - Packard, Chris J.

AU - Caslake, Muriel J.

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AB - The association between possession of the APOE epsilon4 allele and unfavourable outcome after traumatic brain injury (TBI) suggests that the apolipoprotein E protein (apoE) plays a key role in the response of the human brain to injury. ApoE is known to regulate cholesterol metabolism in the periphery through its action as a ligand for receptor mediated uptake of lipoprotein particles (Lps). Greater understanding of cholesterol metabolism in the human central nervous system may identify novel treatment strategies applicable to acute brain injury. We report findings from the analysis of lipoproteins in the cerebrospinal fluid (CSF) of patients with TBI and non-injured controls, testing the hypothesis that remodeling of CSF lipoproteins reflects the response of the brain to TBI. CSF Lps were isolated from the CSF of controls and patients with severe TBI by size exclusion chromatography, and the lipoprotein fractions analysed for cholesterol, phospholipid, apoAI, and apoE. There was a marked decrease in apoE containing Lps in the TBI CSF compared to controls (p=0.002). After TBI there was no significant decrease in apoAI containing CSF Lps (CSF LpAI), but the apoAI resided on smaller sized particles than in control CSF. There was a population of very small sized Lps in TBI CSF, which were associated with the increased cholesterol (p=0.0001) and phospholipid (p=0.040) seen after TBI. The dramatic loss of apoE containing Lps from the CSF, and the substantial increase in CSF cholesterol, support the concept that apoE and cholesterol metabolism are intimately linked in the context of acute brain injury. Treatment strategies targeting CNS lipid transport, required for neuronal sprouting and synaptogenesis, may be applicable to traumatic brain injury.

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KW - Adult

KW - Apolipoprotein A-I

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KW - Brain Injuries

KW - Cholesterol

KW - Chromatography, Gel

KW - Humans

KW - Lipoproteins

KW - Middle Aged

KW - Phospholipids

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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