Influence of apoptosis on neurological outcome following traumatic cerebral contusion

Nathoo, Narendra; Narotam, Pradeep K; Agrawal, Deepak; Connolly, Catherine; Dellen, James R. van; Barnett, Gene H.; Chetty, Runjan

doi:10.3171/jns.2004.101.2.0233

Cited by 56 publications

(46 citation statements)

References 30 publications

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“…According to previous reports, 1.5 to 5% of cells in the adult artery have cleaved caspase-3 immunoreactivity (12,20). Control brain samples that were obtained at surgery showed cleaved caspase-3 immunoreactivity (8,22). Taking all these limits into consideration, we see that our data in this article is not inadequate and did not indicate that only significant degradation in the control.…”

Section: Discussioncontrasting

confidence: 47%

Proliferative Activity through Extracellular Signal-regulated Kinase of Smooth Muscle Cells in Vascular Walls of Cerebral Arteriovenous Malformations

et al. 2006

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Section: Discussioncontrasting

confidence: 47%

Proliferative Activity through Extracellular Signal-regulated Kinase of Smooth Muscle Cells in Vascular Walls of Cerebral Arteriovenous Malformations

et al. 2006

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“…It contributes to neuronal loss and correlates with neurologic outcome (21,22). However, the exact mechanism by which mechanical trauma induces apoptosis is unknown.…”

Section: Discussionmentioning

confidence: 98%

Ubiquitin immunoreactivity in cerebrospinal fluid after traumatic brain injury: Clinical and experimental findings

Majetschak

King

Krehmeier

et al. 2005

Critical Care Medicine

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CSF ubiquitin levels are increased more than four-fold in patients after TBI and nontraumatic subarachnoid hemorrhage. Peak CSF ubiquitin measurements in patients with TBI probably underestimated the actual peak, on the basis of data from the animal model. The progressive rise in CSF ubiquitin in patients with TBI who died suggests that lack of clearance could reflect lethal progression to irreversible brain damage. Erythrolysis is one potential source of CSF ubiquitin.

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“…Factors affecting apoptosis, particularly cytochrome-c-mediated caspase 3 activation, may also influence ␣ -synuclein levels and its conformational status. Apoptotic cell death following TBI is well documented [Darwish and Amiridze, 2010;Huang et al, 2009;Jia et al, 2009;Nathoo et al, 2004]. In addition, levels of CSF cytochrome c are increased at 4 days after TBI in females, in nonaccidental head injury victims and in patients with a Glasgow Coma Scale (GCS) score of 6 5 versus 3 or 4 [Satchell et al, 2005].…”

Section: Introductionmentioning

confidence: 92%

“…In addition, levels of CSF cytochrome c are increased at 4 days after TBI in females, in nonaccidental head injury victims and in patients with a Glasgow Coma Scale (GCS) score of 6 5 versus 3 or 4 [Satchell et al, 2005]. Injury degree and predicted functional outcome have also correlated with the activation of proapoptotic triggers in humans and animal models [Darwish and Amiridze, 2010;Knoblach et al, 2002;Nathoo et al, 2004]. Based on these previous findings, age, gender, mechanism of injury, time and degree of initial insult may all influence extracellular ␣ -synuclein levels.…”

Section: Introductionmentioning

confidence: 92%

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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Influence of apoptosis on neurological outcome following traumatic cerebral contusion

Abstract: The present findings confirm apoptosis in the PIZ of traumatic cerebral contusions and indicate that this form of cell death can influence neurological outcome following a TBI.

Cited by 56 publications

References 30 publications

Proliferative Activity through Extracellular Signal-regulated Kinase of Smooth Muscle Cells in Vascular Walls of Cerebral Arteriovenous Malformations

Proliferative Activity through Extracellular Signal-regulated Kinase of Smooth Muscle Cells in Vascular Walls of Cerebral Arteriovenous Malformations

Ubiquitin immunoreactivity in cerebrospinal fluid after traumatic brain injury: Clinical and experimental findings

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

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