| 1. |
- Czeiter, Endre, et al.
(författare)
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Traumatic axonal injury in the spinal cord evoked by traumatic brain injury
- 2008
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 25:3, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- Although it is well known that traumatic brain injury (TBI) evokes traumatic axonal injury (TAI) within the brain, TBI-induced axonal damage in the spinal cord (SC) has been less extensively investigated. Detection of such axonal injury in the spinal cord would further the complexity of TBI while also challenging some functional neurobehavioral endpoints frequently used to assess recovery in various models of TBI. To assess TAI in the spinal cord associated with TBI, we analyzed the craniocervical junction (CCJ), cervico-thoracic (CT), and thoraco-lumber (ThL) spinal cord in a rodent model of impact acceleration of TBI of varying severities. Rats were transcardially fixed with aldehydes at 2, 6, and 24 h post-injury (n = 36); each group included on sham-injured rodent. Semi-serial vibratome sections were reacted with antibodies targeting TAI via alteration in cytoskeletal integrity or impaired axonal transport. Consistent with previous observations in this model, the CCJ contained numerous injured axons. Immunoreactive, damaged axonal profiles were also detected as caudal, as the ThL spinal cord displayed morphological characteristics entirely consistent with those described in the brainstem and the CCJ. Quantitative analyses demonstrated that the occurrence and extent of TAI is positively associated with the impact/energy of injury and negatively with the distance from the brainstem. These observations show that TBI can evoke TAI in regions remote from the injury site, including the spinal cord itself. This finding is relevant to shaken baby syndrome as well as during the analysis of data in functional recovery in various models of TBI.
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| 2. |
- Kövesdi, Erzsébet, et al.
(författare)
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A novel PARP inhibitor L-2286 in a rat model of impact acceleration head injury : an immunohistochemical and behavioral study
- 2010
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 11:4, s. 1253-1268
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Tidskriftsartikel (refereegranskat)abstract
- We examined the neuro/axono-protective potential of a novel poly (ADP-ribose) polymerase (PARP) inhibitor L-2286 in a rat impact acceleration brain injury model. Male Wistar rats (n = 70) weighing 300-350 grams were used to determine the most effective intracerebroventricular (i.c.v.) dose of L-2286 administered 30 min after injury, and to test the neuroprotective effect at two time points (immediately, and 30 min after injury). The neuroprotective effect of L-2286 was tested using immunohistochemical (amyloid precursor protein and mid-sized mouse anti-neurofilament clone RMO-14.9 antibody) and behavioral tests (beam-balance, open-field and elevated plus maze). At both time-points, a 100 microg/rat dose of i.c.v. L-2286 significantly (p < 0.05) reduced the density of damaged axons in the corticospinal tract and medial longitudinal fascicle compared to controls. In the behavioral tests, treatment 30 min post-injury improved motor function, while the level of anxiety was reduced in both treatment protocols.
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| 3. |
- Kövesdi, Erzsébet, et al.
(författare)
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Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics
- 2010
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 152:1, s. 1-17
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Forskningsöversikt (refereegranskat)abstract
- Purpose: This review summarizes protein biomarkers in mild and severe traumatic brain injury in adults and children and presents a strategy for conducting rationally designed clinical studies on biomarkers in head trauma.Methods: We performed an electronic search of the National Library of Medicine's MEDLINE and Biomedical Library of University of Pennsylvania database in March 2008 using a search heading of traumatic head injury and protein biomarkers. The search was focused especially on protein degradation products (spectrin breakdown product, c-tau, amyloid-beta(1-42)) in the last 10 years, but recent data on "classical" markers (S-100B, neuron-specific enolase, etc.) were also examined.Results: We identified 85 articles focusing on clinical use of biomarkers; 58 articles were prospective cohort studies with injury and/or outcome assessment.Conclusions: We conclude that only S-100B in severe traumatic brain injury has consistently demonstrated the ability to predict injury and outcome in adults. The number of studies with protein degradation products is insufficient especially in the pediatric care. Cohort studies with well-defined end points and further neuroproteomic search for biomarkers in mild injury should be triggered. After critically reviewing the study designs, we found that large homogenous patient populations, consistent injury, and outcome measures prospectively determined cutoff values, and a combined use of different predictors should be considered in future studies.
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