Evaluation of apoptosis in cerebrospinal fluid of patients with severe head injury

Uzan, Mustafa; Erman, Hayriye; Tanrıverdi, Taner; Sanuş, Galip Zihni; Kafadar, Ali; Uzun, Hafize

doi:10.1007/s00701-006-0887-1

Cited by 55 publications

(41 citation statements)

References 33 publications

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“…A larger study population with more frequent ␣ -synuclein sampling would be instrumental in accomplishing this. Finally, mitochondrial dysfunction, inclusive and exclusive of cytochrome c release, is also an important factor in secondary injury following TBI [Robertson et al, 2009;Uzan et al, 2006]. TH is a promising intervention protecting mitochondrial viability in animal models of ischemic injury [Canevari et al, 1999].…”

Section: Discussionmentioning

confidence: 99%

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

Su¹,

Bell²,

Wisniewski

et al. 2010

Dev Neurosci

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α-Synuclein is one of the most abundant proteins in presynaptic terminals. Normal expression of α-synuclein is essential for neuronal survival and it prevents the initiation of apoptosis in neurons through covalent cross-linking of cytochrome c released from mitochondria. Exocytosis of α-synuclein occurs with neuronal mitochondrial dysfunction, making its detection in cerebrospinal fluid (CSF) of children after severe traumatic brain injury (TBI) a potentially important marker of injury. Experimental therapeutic hypothermia (TH) improves mitochondrial function and attenuates cell death, and therefore may also affect CSF α-synuclein concentrations. We assessed α-synuclein levels in CSF of 47 infants and children with severe TBI using a commercial ELISA for detection of monomeric protein. 23 patients were randomized to TH based on published protocols where cooling (32–33°C) was initiated within 6–24 h, maintained for 48 h, and then followed by slow rewarming. CSF samples were obtained continuously via an intraventricular catheter for 6 days after TBI. Control CSF (n = 9) was sampled from children receiving lumbar puncture for CSF analysis of infection that was proven negative. Associations of initial Glasgow Coma Scale (GCS) score, age, gender, treatment, mechanism of injury and Glasgow Outcome Scale (GOS) score with CSF α-synuclein were compared by multivariate regression analysis. CSF α-synuclein levels were elevated in TBI patients compared to controls (p = 0.0093), with a temporal profile showing an early, approximately 5-fold increase on days 1–3 followed by a delayed, >10-fold increase on days 4–6 versus control. α-Synuclein levels were higher in patients treated with normothermia versus hypothermia (p = 0.0033), in patients aged <4 years versus ≧4 years (p < 0.0001), in females versus males (p = 0.0007), in nonaccidental TBI versus accidental TBI victims (p = 0.0003), and in patients with global versus focal injury on computed tomography of the brain (p = 0.046). Comparisons of CSF α-synuclein levels with initial GCS and GOS scores were not statistically significant. Further studies are needed to evaluate the conformational status of α-synuclein in CSF, and whether TH affects α-synuclein aggregation.

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Section: Discussionmentioning

confidence: 99%

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

Su¹,

Bell²,

Wisniewski

et al. 2010

Dev Neurosci

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show abstract

“…correlated with increased intracranial pressure. Soluble Fas and caspase-3 peaks coincided on day 5 after trauma, with significant association between soluble Fas and caspase-3 increase [9]. Data also showed that detection of markers of inflammation in the CSF of patients with TBI.…”

Section: Discussionmentioning

confidence: 63%

Detectable Levels of Cytochrome c and Activated Caspase-9 in Cerebrospinal Fluid after Human Traumatic Brain Injury

Darwish

Amiridze

2010

Neurocrit Care

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“…However, some of the proteins such as cystatin-C, alpha-1-antitrypsin and other housekeeping proteins are usually also detected in normal CSF and should not be regarded as to be related specifically to TBI. In order to assess how many potential biomarkers for TBI that could be detected with the HLL, a literature search was conducted and is summarized in Table 2 [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Only proteins reported to have a down/up-regulation in CSF or human brain tissue in relation to an inflicted trauma to the head are included in the table.…”

Section: Resultsmentioning

confidence: 99%

Mining ventricular cerebrospinal fluid from patients with traumatic brain injury using hexapeptide ligand libraries to search for trauma biomarkers

Sjödin

Bergquist

Wetterhall

2010

Journal of Chromatography B

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Evaluation of apoptosis in cerebrospinal fluid of patients with severe head injury

Cited by 55 publications

References 33 publications

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

Detectable Levels of Cytochrome c and Activated Caspase-9 in Cerebrospinal Fluid after Human Traumatic Brain Injury

Mining ventricular cerebrospinal fluid from patients with traumatic brain injury using hexapeptide ligand libraries to search for trauma biomarkers

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