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

Department of Neurosurgery, Center for Medical and Health Sciences, Pécs University, Pécs, Hungary.
Acta Neurochirurgica (Impact Factor: 1.79). 09/2005; 147(8):855-61. DOI: 10.1007/s00701-005-0559-6
Source: PubMed

ABSTRACT 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.
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.
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 2(nd) -3(rd) days after TBI.
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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Andrey Mazarati – Department of Pediatrics, UCLA, USA Claude Wasterlain – Department of Cardiology, UCLA, USA
    Drug Discovery Today Disease Mechanisms 12/2005; 2(4):409-418.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Aim: This article attempts to provide a framework that will help to illustrate the roles of calpains in the process of traumatic brain injury (TBI). Method: This review provides meaningful points about the essential role of calpains in the neuropathological changes that follow TBI, identifies useful biomarkers of calpain activation and states the important roles of calpain in the treatment of TBI. Results: Neuronal calpains can be activated within hours or even minutes following contusive or diffuse brain trauma in animals. It has been suggested that they are early mediators of neuronal damage. Trauma can produce sustained calpain activation. In turn, this may result in axonal degeneration and neuronal death in models of TBI. Calpains can cleave cytoskeletal proteins into stable proteolytic fragments that have been widely used as biomarkers of the activation of calpain. The inhibition of calpains can reduce the functional and behavioural deficits by ameliorating axonal pathology and reducing cell deaths in animal models of TBI. Conclusion: This review concentrates on the current understanding of the role of calpains in neuropathology that has been induced by TBI and the significance of calpains as a therapeutic target for the treatment of primary and secondary injuries that are associated with brain trauma.
    Brain Injury 02/2014; 28(2):133-7. · 1.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine if alpha II-spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period. Prospective observational cohort study. Pediatric cardiac ICU in an urban tertiary care academic center. Neonates with congenital heart disease undergoing surgical repair or palliation. Serial blood sampling for measurement of 120 and 150 kDa spectrin breakdown products. Fourteen neonates with congenital heart disease undergoing cardiac surgery were evaluated. Nine infants underwent open-heart surgery and five underwent closed-heart surgery. Serum spectrin breakdown products were measured with sandwich enzyme-linked immunosorbent assay preoperatively and then 6, 24, 48, 72, and 96 hours following surgery. Brain imaging was obtained as part of routine clinical care in 12 patients preoperatively and six patients postoperatively. Six patients had normal preoperative imaging (three closed-heart surgery and three open-heart surgery), whereas six had evidence of neurologic injury prior to surgery (one closed-heart surgery and five open-heart surgery). Only one patient had a postoperative imaging study that lacked injury. All others demonstrated infarction or hemorrhage. Spectrin breakdown product 120 kDa significantly increased 24 hours after open-heart surgery compared to preoperative values and time-matched closed-heart surgery levels. Spectrin breakdown product 150 kDa significantly increased 6 hours after open-heart surgery compared to preoperative values. There was no significant change in spectrin breakdown products following closed-heart surgery. Peak spectrin breakdown products significantly increased following open-heart surgery compared to closed-heart surgery. Spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period and levels increased to a greater degree in infants following open-heart surgery. These findings suggest that, in future work, serum spectrin breakdown products may potentially be developed as biomarkers for brain necrosis and apoptosis in infants with congenital heart disease.
    Pediatric Critical Care Medicine 01/2014; · 2.33 Impact Factor