Spectrin breakdown products in the cerebrospinal fluid in severe head injury - Preliminary observations

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Abstract

Background. Calcium-induced proteolytic processes are considered key players in the progressive pathobiology of traumatic brain injury (TBI). Activation of calpain and caspases after TBI leads to the cleavage of cytoskeletal proteins such as non-erythroid alpha II-spectrin. Recent reports demonstrate that the levels of spectrin and spectrin breakdown products (SBDPs) are elevated in vitro after mechanical injury, in the cerebrospinal fluid (CSF) and brain tissue following experimental TBI, and in human brain tissue after TBI. Methods. This study was initiated to detect spectrin and SBDP accumulation in the ventricular CSF of 12 severe TBI-patients with raised intracranial pressure (ICP). Nine patients with non-traumatically elevated ICP and 5 undergoing diagnostic lumbar puncture (LP) served as controls. Intact spectrin and calpain and caspase specific SBDPs in CSF collected once a day over a several day period were assessed via Western blot analysis. Parameters of severity and outcome such as ICP, Glasgow Coma Scale and Glasgow Outcome Scale were also monitored in order to reveal a potential correlation between these CSF markers and clinical parameters. Results. In control patients undergone LP no immunoreactivity was detected. Non-erythroid alpha-II-spectrin and SBDP occurred more frequently and their level was significantly higher in the CSF of TBI patients than in other pathological conditions associated with raised ICP. Those TBI patients followed for several days post-injury revealed a consistent temporal pattern for protein accumulation with the highest level achieved on the 2nd-3rd days after TBI. Conclusion. Elevation of calpain and caspase specific SBDPs is a significant finding in TBI patients indicating that intact brain spectrin- and SBDP-levels are closely associated with the specific neurochemical processes evoked by TBI. The results strongly support the potential utility of these surrogate markers in the clinical monitoring of patients with severe TBI and provide further evidence of the role of calcium-induced, calpain- and caspase-mediated structural proteolysis in TBI.

Original languageEnglish
Pages (from-to)855-860
Number of pages6
JournalActa Neurochirurgica
Volume147
Issue number8
DOIs
Publication statusPublished - Aug 2005

Fingerprint

Spectrin
Craniocerebral Trauma
Cerebrospinal Fluid
Calpain
Caspases
Intracranial Pressure
Spinal Puncture
Traumatic Brain Injury
Brain
Biomarkers
Glasgow Outcome Scale
Calcium
Glasgow Coma Scale
Intracranial Hypertension
Cytoskeletal Proteins
Wounds and Injuries
Physiologic Monitoring
Proteolysis

Keywords

  • Calpain
  • Caspase
  • Cerebrospinal fluid
  • Human
  • Spectrin
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

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title = "Spectrin breakdown products in the cerebrospinal fluid in severe head injury - Preliminary observations",
abstract = "Background. Calcium-induced proteolytic processes are considered key players in the progressive pathobiology of traumatic brain injury (TBI). Activation of calpain and caspases after TBI leads to the cleavage of cytoskeletal proteins such as non-erythroid alpha II-spectrin. Recent reports demonstrate that the levels of spectrin and spectrin breakdown products (SBDPs) are elevated in vitro after mechanical injury, in the cerebrospinal fluid (CSF) and brain tissue following experimental TBI, and in human brain tissue after TBI. Methods. This study was initiated to detect spectrin and SBDP accumulation in the ventricular CSF of 12 severe TBI-patients with raised intracranial pressure (ICP). Nine patients with non-traumatically elevated ICP and 5 undergoing diagnostic lumbar puncture (LP) served as controls. Intact spectrin and calpain and caspase specific SBDPs in CSF collected once a day over a several day period were assessed via Western blot analysis. Parameters of severity and outcome such as ICP, Glasgow Coma Scale and Glasgow Outcome Scale were also monitored in order to reveal a potential correlation between these CSF markers and clinical parameters. Results. In control patients undergone LP no immunoreactivity was detected. Non-erythroid alpha-II-spectrin and SBDP occurred more frequently and their level was significantly higher in the CSF of TBI patients than in other pathological conditions associated with raised ICP. Those TBI patients followed for several days post-injury revealed a consistent temporal pattern for protein accumulation with the highest level achieved on the 2nd-3rd days after TBI. Conclusion. Elevation of calpain and caspase specific SBDPs is a significant finding in TBI patients indicating that intact brain spectrin- and SBDP-levels are closely associated with the specific neurochemical processes evoked by TBI. The results strongly support the potential utility of these surrogate markers in the clinical monitoring of patients with severe TBI and provide further evidence of the role of calcium-induced, calpain- and caspase-mediated structural proteolysis in TBI.",
keywords = "Calpain, Caspase, Cerebrospinal fluid, Human, Spectrin, Traumatic brain injury",
author = "O. Farkas and B. Polg{\'a}r and J. Szekeres-Barth{\'o} and T. D{\'o}czi and Povlishock, {J. T.} and A. B{\"u}ki",
year = "2005",
month = "8",
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language = "English",
volume = "147",
pages = "855--860",
journal = "Acta Neurochirurgica",
issn = "0001-6268",
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TY - JOUR

T1 - Spectrin breakdown products in the cerebrospinal fluid in severe head injury - Preliminary observations

AU - Farkas, O.

AU - Polgár, B.

AU - Szekeres-Barthó, J.

AU - Dóczi, T.

AU - Povlishock, J. T.

AU - Büki, A.

PY - 2005/8

Y1 - 2005/8

N2 - Background. Calcium-induced proteolytic processes are considered key players in the progressive pathobiology of traumatic brain injury (TBI). Activation of calpain and caspases after TBI leads to the cleavage of cytoskeletal proteins such as non-erythroid alpha II-spectrin. Recent reports demonstrate that the levels of spectrin and spectrin breakdown products (SBDPs) are elevated in vitro after mechanical injury, in the cerebrospinal fluid (CSF) and brain tissue following experimental TBI, and in human brain tissue after TBI. Methods. This study was initiated to detect spectrin and SBDP accumulation in the ventricular CSF of 12 severe TBI-patients with raised intracranial pressure (ICP). Nine patients with non-traumatically elevated ICP and 5 undergoing diagnostic lumbar puncture (LP) served as controls. Intact spectrin and calpain and caspase specific SBDPs in CSF collected once a day over a several day period were assessed via Western blot analysis. Parameters of severity and outcome such as ICP, Glasgow Coma Scale and Glasgow Outcome Scale were also monitored in order to reveal a potential correlation between these CSF markers and clinical parameters. Results. In control patients undergone LP no immunoreactivity was detected. Non-erythroid alpha-II-spectrin and SBDP occurred more frequently and their level was significantly higher in the CSF of TBI patients than in other pathological conditions associated with raised ICP. Those TBI patients followed for several days post-injury revealed a consistent temporal pattern for protein accumulation with the highest level achieved on the 2nd-3rd days after TBI. Conclusion. Elevation of calpain and caspase specific SBDPs is a significant finding in TBI patients indicating that intact brain spectrin- and SBDP-levels are closely associated with the specific neurochemical processes evoked by TBI. The results strongly support the potential utility of these surrogate markers in the clinical monitoring of patients with severe TBI and provide further evidence of the role of calcium-induced, calpain- and caspase-mediated structural proteolysis in TBI.

AB - Background. Calcium-induced proteolytic processes are considered key players in the progressive pathobiology of traumatic brain injury (TBI). Activation of calpain and caspases after TBI leads to the cleavage of cytoskeletal proteins such as non-erythroid alpha II-spectrin. Recent reports demonstrate that the levels of spectrin and spectrin breakdown products (SBDPs) are elevated in vitro after mechanical injury, in the cerebrospinal fluid (CSF) and brain tissue following experimental TBI, and in human brain tissue after TBI. Methods. This study was initiated to detect spectrin and SBDP accumulation in the ventricular CSF of 12 severe TBI-patients with raised intracranial pressure (ICP). Nine patients with non-traumatically elevated ICP and 5 undergoing diagnostic lumbar puncture (LP) served as controls. Intact spectrin and calpain and caspase specific SBDPs in CSF collected once a day over a several day period were assessed via Western blot analysis. Parameters of severity and outcome such as ICP, Glasgow Coma Scale and Glasgow Outcome Scale were also monitored in order to reveal a potential correlation between these CSF markers and clinical parameters. Results. In control patients undergone LP no immunoreactivity was detected. Non-erythroid alpha-II-spectrin and SBDP occurred more frequently and their level was significantly higher in the CSF of TBI patients than in other pathological conditions associated with raised ICP. Those TBI patients followed for several days post-injury revealed a consistent temporal pattern for protein accumulation with the highest level achieved on the 2nd-3rd days after TBI. Conclusion. Elevation of calpain and caspase specific SBDPs is a significant finding in TBI patients indicating that intact brain spectrin- and SBDP-levels are closely associated with the specific neurochemical processes evoked by TBI. The results strongly support the potential utility of these surrogate markers in the clinical monitoring of patients with severe TBI and provide further evidence of the role of calcium-induced, calpain- and caspase-mediated structural proteolysis in TBI.

KW - Calpain

KW - Caspase

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KW - Human

KW - Spectrin

KW - Traumatic brain injury

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