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Erschienen in: Child's Nervous System 1/2009

01.01.2009 | Original Paper

Modulating effect of apolipoprotein E polymorphisms on secondary brain insult and outcome after childhood brain trauma

verfasst von: T. Y. M. Lo, P. A. Jones, I. R. Chambers, T. F. Beattie, R. Forsyth, A. D. Mendelow, R. A. Minns

Erschienen in: Child's Nervous System | Ausgabe 1/2009

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Abstract

Objective

The aim of this study was to determine the relationship between apolipoprotein E (APO E) alleles, the amount of cerebral perfusion pressure (CPP) insult and outcome in children after brain trauma.

Materials and methods

In a prospective two-centre case–control study, the APO E genotypes of 65 critically ill children admitted after brain trauma were correlated with age-related CPP insult quantification, conscious state at the time of discharge from intensive care and global outcome at 6 months post-injury. One hundred sixty healthy age- and sex-matched children were genotyped as controls.

Results

The CPP insult level among the e4 carriers with poor outcome was significantly less than the non-e4 carriers (p = 0.03). Homozygotic e3 patients with good recovery did so despite having suffered nearly 26 times more CPP insult than those who were not e3 homzygous (p = 0.02).

Conclusion

Different APO E alleles may potentially affect cerebral ischaemic tolerance differently in children after brain trauma.
Literatur
1.
Zurück zum Zitat Chambers IR, Treadwell L, Mendelow AD (2000) The cause and incidence of secondary insults in severely head-injured adults and children. Br J Neurosurg 14:424–431PubMedCrossRef Chambers IR, Treadwell L, Mendelow AD (2000) The cause and incidence of secondary insults in severely head-injured adults and children. Br J Neurosurg 14:424–431PubMedCrossRef
2.
Zurück zum Zitat Jones PA, Andrews PJ, Easton VJ, Minns RA (2003) Traumatic brain injury in childhood: intensive care time series data and outcome. Br J Neurosurg 17:29–39PubMedCrossRef Jones PA, Andrews PJ, Easton VJ, Minns RA (2003) Traumatic brain injury in childhood: intensive care time series data and outcome. Br J Neurosurg 17:29–39PubMedCrossRef
3.
Zurück zum Zitat Chesnut RM, Marshall LF, Klauber MR, Blunt BA, Baldwin N, Eisenberg HM, Jane JA, Marmarou A, Foulkes MA (1993) The role of secondary brain injury in determining outcome from severe head injury. J Trauma 34:216–222PubMedCrossRef Chesnut RM, Marshall LF, Klauber MR, Blunt BA, Baldwin N, Eisenberg HM, Jane JA, Marmarou A, Foulkes MA (1993) The role of secondary brain injury in determining outcome from severe head injury. J Trauma 34:216–222PubMedCrossRef
4.
Zurück zum Zitat Miller JD, Becker DP (1982) Secondary insults to the injured brain. J R Coll Surg Edinb 27:292–298PubMed Miller JD, Becker DP (1982) Secondary insults to the injured brain. J R Coll Surg Edinb 27:292–298PubMed
5.
Zurück zum Zitat Teasdale GM, Nicoll JA, Murray G, Fiddes M (1997) Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350:1069–1071PubMedCrossRef Teasdale GM, Nicoll JA, Murray G, Fiddes M (1997) Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350:1069–1071PubMedCrossRef
6.
Zurück zum Zitat Alexander S, Kerr ME, Kim Y, Kamboh MI, Beers SR, Conley YP (2007) Apolipoprotein E4 allele presence and functional outcome after severe traumatic brain injury. J Neurotrauma 24:790–797PubMedCrossRef Alexander S, Kerr ME, Kim Y, Kamboh MI, Beers SR, Conley YP (2007) Apolipoprotein E4 allele presence and functional outcome after severe traumatic brain injury. J Neurotrauma 24:790–797PubMedCrossRef
7.
Zurück zum Zitat Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J, Babaey S, Yehuda B, Groswasser Z (1999) Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology 52:244–248PubMed Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J, Babaey S, Yehuda B, Groswasser Z (1999) Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology 52:244–248PubMed
8.
Zurück zum Zitat Teasdale GM, Murray GD, Nicoll JA (2005) The association between APOE epsilon4, age and outcome after head injury: a prospective cohort study. Brain 128:2556–2561PubMedCrossRef Teasdale GM, Murray GD, Nicoll JA (2005) The association between APOE epsilon4, age and outcome after head injury: a prospective cohort study. Brain 128:2556–2561PubMedCrossRef
9.
Zurück zum Zitat Colton CA, Needham LK, Brown C, Cook D, Rasheed K, Burke JR, Strittmatter WJ, Schmechel DE, Vitek MP (2004) APOE genotype-specific differences in human and mouse macrophage nitric oxide production. J Neuroimmunol 147:62–67PubMedCrossRef Colton CA, Needham LK, Brown C, Cook D, Rasheed K, Burke JR, Strittmatter WJ, Schmechel DE, Vitek MP (2004) APOE genotype-specific differences in human and mouse macrophage nitric oxide production. J Neuroimmunol 147:62–67PubMedCrossRef
10.
Zurück zum Zitat Mazur-Kolecka B, Dickson D, Frackowiak J (2006) Induction of vascular amyloidosis-beta by oxidative stress depends on APOE genotype. Neurobiol Aging 27:804–814PubMedCrossRef Mazur-Kolecka B, Dickson D, Frackowiak J (2006) Induction of vascular amyloidosis-beta by oxidative stress depends on APOE genotype. Neurobiol Aging 27:804–814PubMedCrossRef
11.
Zurück zum Zitat Aono M, Lee Y, Grant ER, Zivin RA, Pearlstein RD, Warner DS, Bennett ER, Laskowitz DT (2002) Apolipoprotein E protects against NMDA excitotoxicity. Neurobiol Dis 11:214–220PubMedCrossRef Aono M, Lee Y, Grant ER, Zivin RA, Pearlstein RD, Warner DS, Bennett ER, Laskowitz DT (2002) Apolipoprotein E protects against NMDA excitotoxicity. Neurobiol Dis 11:214–220PubMedCrossRef
12.
Zurück zum Zitat Mattson MP (1997) Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev 77:1081–1132PubMed Mattson MP (1997) Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev 77:1081–1132PubMed
13.
Zurück zum Zitat Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31:545–548PubMed Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31:545–548PubMed
14.
Zurück zum Zitat Chambers IR, Jones PA, Lo TY, Forsyth RJ, Fulton B, Andrews PJ, Mendelow AD, Minns RA (2006) Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury. J Neurol Neurosurg Psychiatry 77:234–240PubMedCrossRef Chambers IR, Jones PA, Lo TY, Forsyth RJ, Fulton B, Andrews PJ, Mendelow AD, Minns RA (2006) Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury. J Neurol Neurosurg Psychiatry 77:234–240PubMedCrossRef
15.
Zurück zum Zitat Cumming AM, Robertson FW (1984) Polymorphism at the apoprotein-E locus in relation to risk of coronary disease. Clin Genet 25:310–313PubMedCrossRef Cumming AM, Robertson FW (1984) Polymorphism at the apoprotein-E locus in relation to risk of coronary disease. Clin Genet 25:310–313PubMedCrossRef
16.
Zurück zum Zitat Chiang MF, Chang JG, Hu CJ (2003) Association between apolipoprotein E genotype and outcome of traumatic brain injury. Acta Neurochir (Wien) 145:649–653 discussion 53–4CrossRef Chiang MF, Chang JG, Hu CJ (2003) Association between apolipoprotein E genotype and outcome of traumatic brain injury. Acta Neurochir (Wien) 145:649–653 discussion 53–4CrossRef
17.
Zurück zum Zitat Lynch JR, Pineda JA, Morgan D, Zhang L, Warner DS, Benveniste H, Laskowitz DT (2002) Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Ann Neurol 51:113–117PubMedCrossRef Lynch JR, Pineda JA, Morgan D, Zhang L, Warner DS, Benveniste H, Laskowitz DT (2002) Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Ann Neurol 51:113–117PubMedCrossRef
18.
Zurück zum Zitat McCarron MO, Hoffmann KL, DeLong DM, Gray L, Saunders AM, Alberts MJ (1999) Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes. Neurology 53:2176–2179PubMed McCarron MO, Hoffmann KL, DeLong DM, Gray L, Saunders AM, Alberts MJ (1999) Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes. Neurology 53:2176–2179PubMed
19.
Zurück zum Zitat Quinn TJ, Smith C, Murray L, Stewart J, Nicoll JA, Graham DI (2004) There is no evidence of an association in children and teenagers between the apolipoprotein E epsilon4 allele and post-traumatic brain swelling. Neuropathol Appl Neurobiol 30:569–575PubMedCrossRef Quinn TJ, Smith C, Murray L, Stewart J, Nicoll JA, Graham DI (2004) There is no evidence of an association in children and teenagers between the apolipoprotein E epsilon4 allele and post-traumatic brain swelling. Neuropathol Appl Neurobiol 30:569–575PubMedCrossRef
20.
Zurück zum Zitat Rantala M, Savolainen MJ, Kervinen K, Kesaniemi YA (1997) Apolipoprotein E phenotype and diet-induced alteration in blood pressure. Am J Clin Nutr 65:543–550PubMed Rantala M, Savolainen MJ, Kervinen K, Kesaniemi YA (1997) Apolipoprotein E phenotype and diet-induced alteration in blood pressure. Am J Clin Nutr 65:543–550PubMed
21.
Zurück zum Zitat Uusitupa M, Sarkkinen E, Kervinen K, Kesaniemi YA (1994) Apolipoprotein E phenotype and blood pressure. Lancet 343:57PubMedCrossRef Uusitupa M, Sarkkinen E, Kervinen K, Kesaniemi YA (1994) Apolipoprotein E phenotype and blood pressure. Lancet 343:57PubMedCrossRef
22.
Zurück zum Zitat Uusitupa MI, Karhunen L, Rissanen A, Franssila-Kallunki A, Niskanen L, Kervinen K, Kesaniemi YA (1996) Apolipoprotein E phenotype modifies metabolic and hemodynamic abnormalities related to central obesity in women. Am J Clin Nutr 64:131–136PubMed Uusitupa MI, Karhunen L, Rissanen A, Franssila-Kallunki A, Niskanen L, Kervinen K, Kesaniemi YA (1996) Apolipoprotein E phenotype modifies metabolic and hemodynamic abnormalities related to central obesity in women. Am J Clin Nutr 64:131–136PubMed
23.
Zurück zum Zitat Couderc R, Mahieux F, Bailleul S, Fenelon G, Mary R, Fermanian J (1993) Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case–control study. Stroke 24:661–664PubMed Couderc R, Mahieux F, Bailleul S, Fenelon G, Mary R, Fermanian J (1993) Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case–control study. Stroke 24:661–664PubMed
24.
Zurück zum Zitat de Knijff P, Boomsma DI, Feskens EJ, Jespersen J, Johansen LG, Kluft C, Kromhout D, Havekes LM (1994) Apolipoprotein E phenotype and blood pressure. Lancet 343:1234–1235PubMedCrossRef de Knijff P, Boomsma DI, Feskens EJ, Jespersen J, Johansen LG, Kluft C, Kromhout D, Havekes LM (1994) Apolipoprotein E phenotype and blood pressure. Lancet 343:1234–1235PubMedCrossRef
25.
Zurück zum Zitat Eto M, Watanabe K, Makino I (1989) Increased frequencies of apolipoprotein epsilon 2 and epsilon 4 alleles in patients with ischemic heart disease. Clin Genet 36:183–188PubMed Eto M, Watanabe K, Makino I (1989) Increased frequencies of apolipoprotein epsilon 2 and epsilon 4 alleles in patients with ischemic heart disease. Clin Genet 36:183–188PubMed
26.
Zurück zum Zitat Liaquat I, Dunn LT, Nicoll JA, Teasdale GM, Norrie JD (2002) Effect of apolipoprotein E genotype on hematoma volume after trauma. J Neurosurg 96:90–96PubMed Liaquat I, Dunn LT, Nicoll JA, Teasdale GM, Norrie JD (2002) Effect of apolipoprotein E genotype on hematoma volume after trauma. J Neurosurg 96:90–96PubMed
27.
Zurück zum Zitat Smith C, Graham DI, Murray LS, Stewart J, Nicoll JA (2006) Association of APOE e4 and cerebrovascular pathology in traumatic brain injury. J Neurol Neurosurg Psychiatry 77:363–366PubMedCrossRef Smith C, Graham DI, Murray LS, Stewart J, Nicoll JA (2006) Association of APOE e4 and cerebrovascular pathology in traumatic brain injury. J Neurol Neurosurg Psychiatry 77:363–366PubMedCrossRef
28.
Zurück zum Zitat van Dyck CH, Gelernter J, MacAvoy MG, Avery RA, Criden M, Okereke O, Varma P, Seibyl JP, Hoffer PB (1998) Absence of an apolipoprotein E epsilon4 allele is associated with increased parietal regional cerebral blood flow asymmetry in Alzheimer disease. Arch Neurol 55:1460–1466PubMedCrossRef van Dyck CH, Gelernter J, MacAvoy MG, Avery RA, Criden M, Okereke O, Varma P, Seibyl JP, Hoffer PB (1998) Absence of an apolipoprotein E epsilon4 allele is associated with increased parietal regional cerebral blood flow asymmetry in Alzheimer disease. Arch Neurol 55:1460–1466PubMedCrossRef
29.
Zurück zum Zitat Scarmeas N, Habeck CG, Stern Y, Anderson KE (2003) APOE genotype and cerebral blood flow in healthy young individuals. Jama 290:1581–1582PubMedCrossRef Scarmeas N, Habeck CG, Stern Y, Anderson KE (2003) APOE genotype and cerebral blood flow in healthy young individuals. Jama 290:1581–1582PubMedCrossRef
30.
Zurück zum Zitat Sharples PM, Stuart AG, Matthews DS, Aynsley-Green A, Eyre JA (1995) Cerebral blood flow and metabolism in children with severe head injury. Part 1: relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury. J Neurol Neurosurg Psychiatry 58:145–152PubMedCrossRef Sharples PM, Stuart AG, Matthews DS, Aynsley-Green A, Eyre JA (1995) Cerebral blood flow and metabolism in children with severe head injury. Part 1: relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury. J Neurol Neurosurg Psychiatry 58:145–152PubMedCrossRef
31.
Zurück zum Zitat Guo L, LaDu MJ, Van Eldik LJ (2004) A dual role for apolipoprotein e in neuroinflammation: anti- and pro-inflammatory activity. J Mol Neurosci 23:205–212PubMedCrossRef Guo L, LaDu MJ, Van Eldik LJ (2004) A dual role for apolipoprotein e in neuroinflammation: anti- and pro-inflammatory activity. J Mol Neurosci 23:205–212PubMedCrossRef
32.
Zurück zum Zitat Lynch JR, Tang W, Wang H, Vitek MP, Bennett ER, Sullivan PM, Warner DS, Laskowitz DT (2003) APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response. J Biol Chem 278:48529–48533PubMedCrossRef Lynch JR, Tang W, Wang H, Vitek MP, Bennett ER, Sullivan PM, Warner DS, Laskowitz DT (2003) APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response. J Biol Chem 278:48529–48533PubMedCrossRef
33.
Zurück zum Zitat Tziakas DN, Chalikias GK, Antonoglou CO, Veletza S, Tentes IK, Kortsaris AX, Hatseras DI, Kaski JC (2006) Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease. J Am Coll Cardiol 48:2471–2481PubMedCrossRef Tziakas DN, Chalikias GK, Antonoglou CO, Veletza S, Tentes IK, Kortsaris AX, Hatseras DI, Kaski JC (2006) Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease. J Am Coll Cardiol 48:2471–2481PubMedCrossRef
34.
Zurück zum Zitat Sabo T, Lomnitski L, Nyska A, Beni S, Maronpot RR, Shohami E, Roses AD, Michaelson DM (2000) Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: the allele E3 is neuroprotective whereas E4 increases fatalities. Neuroscience 101:879–884PubMedCrossRef Sabo T, Lomnitski L, Nyska A, Beni S, Maronpot RR, Shohami E, Roses AD, Michaelson DM (2000) Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: the allele E3 is neuroprotective whereas E4 increases fatalities. Neuroscience 101:879–884PubMedCrossRef
35.
Zurück zum Zitat Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8:1–21PubMed Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8:1–21PubMed
36.
Zurück zum Zitat Utermann G, Langenbeck U, Beisiegel U, Weber W (1980) Genetics of the apolipoprotein E system in man. Am J Hum Genet 32:339–347PubMed Utermann G, Langenbeck U, Beisiegel U, Weber W (1980) Genetics of the apolipoprotein E system in man. Am J Hum Genet 32:339–347PubMed
37.
Zurück zum Zitat Becher JC, Bell JE, McIntosh N, Keeling JW (2005) Distribution of apolipoprotein E alleles in a Scottish healthy newborn population. Biol Neonate 88:164–167PubMedCrossRef Becher JC, Bell JE, McIntosh N, Keeling JW (2005) Distribution of apolipoprotein E alleles in a Scottish healthy newborn population. Biol Neonate 88:164–167PubMedCrossRef
Metadaten
Titel
Modulating effect of apolipoprotein E polymorphisms on secondary brain insult and outcome after childhood brain trauma
verfasst von
T. Y. M. Lo
P. A. Jones
I. R. Chambers
T. F. Beattie
R. Forsyth
A. D. Mendelow
R. A. Minns
Publikationsdatum
01.01.2009
Verlag
Springer-Verlag
Erschienen in
Child's Nervous System / Ausgabe 1/2009
Print ISSN: 0256-7040
Elektronische ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-008-0723-4

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