| 1. |
- Czigner, Andrea, et al.
(author)
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Dynamics and regional distribution of c-fos protein expression in rat brain after a closed head injury
- 2004
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In: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 14:2, s. 247-252
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Journal article (peer-reviewed)abstract
- The objective of this study was to define the time- and brain-area-related distribution of c-fos expression in the brain during the first 24 h following a closed head injury in rats. In the control groups (n = 32), only a few c-fos positive nuclei were observed in the brain and the c-fos staining did not change during the next 24 h. In the closed head injury group c-fos-positive cells were rare in the brain regions during the first 30 min. During the next 2 h, the number of c-fos-positive cells increased rapidly in the basal ganglions, the ventricular ependyma cells the corticospinal tract, the area postrema, the cerebral neocortex, and the corpus callosum. The increase was highest in the corpus callosum (317 +/- 44.5 mm(-2)), in the thalamic reticular nucleus (474.8 +/- 49.2 mm(-2)), in the dentate hilus (1090 +/- 187 mm(-2)) and in the cerebral neocortex (992 +/- 93 mm(-2)). Thereafter, the elevated c-fos expression gradually decreased and at 6 h post-closed head injury no significant differences were observed between the controls and the trauma group. We conclude that a closed head injury induces a large, transient increase of c-fos expression in the brain. Since the observed time course and regional differences in c-fos expression are in good agreement with the cognitive and memory deficits observed after human TBI it can be utilized in further investigations, especially to test the effects of various forms of pharmacological or cellular therapy.
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| 2. |
- Büki, Andras, 1966-, et al.
(author)
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A koponyasérülés által kiváltott axonkárosodás és kezelésének lehetóségei : [Therapeutic possibilities in axonal injury caused by head trauma]
- 2002
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In: Orvosi Hetilap. - : Akademiai Kiado Rt.. - 0030-6002 .- 1788-6120. ; 143:10, s. 499-503
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Research review (peer-reviewed)abstract
- Traumatic brain injury is putting an extreme burden on societies all over the world. While surgical and neuro-intensive treatment is traditionally aimed at space occupying or focal lesions, traumatic brain injury is frequently associated with diffuse axonal injury, which significantly contributes to its morbidity and mortality. Current taught appreciates that diffuse axonal injury is a progressive event gradually evolving from focal alterations in axolemmal permeability and the underlying axonal ultrastructure to axonal disconnection, a process amenable of therapeutic interventions. This review is primarily focusing on the clinical/neuroradiological manifestation and our contemporary knowledge of the pathobiology of traumatically evoked (diffuse-) axonal injury with particular emphasize on recent- to date, primarily experimental-therapeutic approaches that in the future might offer potential aid to the head injured.
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| 3. |
- Büki, Andras, 1966-, et al.
(author)
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Cytochrome c release and caspase activation in traumatic axonal injury
- 2000
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In: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 20:8, s. 2825-2834
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Journal article (peer-reviewed)abstract
- Axonal injury is a feature of traumatic brain injury (TBI) contributing to both morbidity and mortality. The traumatic axon injury (TAI) results from focal perturbations of the axolemma, allowing for calcium influx triggering local intraaxonal cytoskeletal and mitochondrial damage. This mitochondrial damage has been posited to cause local bioenergetic failure, leading to axonal failure and disconnection; however, this mitochondrial damage may also lead to the release of cytochrome c (cyto-c), which then activates caspases with significant adverse intraaxonal consequences. In the current communication, we examine this possibility. Rats were subjected to TBI, perfused with aldehydes at 15-360 min after injury, and processed for light microscopic (LM) and electron microscopic (EM) single-labeling immunohistochemistry to detect extramitochondrially localized cytochrome c (cyto-c) and the signature protein of caspase-3 activation (120 kDa breakdown product of alpha-spectrin) in TAI. Combinations of double-labeling fluorescent immunohistochemistry (D-FIHC) were also used to demonstrate colocalization of calpain activation with cyto-c release and caspase-3-induction. In foci of TAI qualitative-quantitative LM demonstrated a parallel, significant increase in cyto-c release and caspase-3 activation over time after injury. EM analysis demonstrated that cyto-c and caspase-3 immunoreactivity were associated with mitochondrial swelling-disruption in sites of TAI. Furthermore, D-IFHC revealed a colocalization of calpain activation, cyto-c release, and caspase-3 induction in these foci, which also revealed progressive TAI. The results demonstrate that cyto-c and caspase-3 participate in the terminal processes of TAI. This suggests that those factors that play a role in the apoptosis in the neuronal soma are also major contributors to the demise of the axonal appendage.
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| 4. |
- Büki, Andras, 1966-, et al.
(author)
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Novel application of tyramide signal amplification (TSA) : ultrastructural visualization of double-labeled immunofluorescent axonal profiles
- 2000
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In: Journal of Histochemistry and Cytochemistry. - : Sage Publications. - 0022-1554 .- 1551-5044. ; 48:1, s. 153-161
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Journal article (peer-reviewed)abstract
- Fluorescent immunocytochemistry (FICC) allows multiple labeling approaches when enzyme-based techniques are difficult to combine, such as in double-labeling experiments targeting small-caliber axonal segments. Nevertheless, the conversion of FICC to a product visible at the electron microscopic (EM) level requires labor-intensive procedures, thus justifying the development of more user-friendly conversion methods. This study was initiated to simplify the conversion of FICC to EM by employing the unique properties of tyramide signal amplification (TSA), which allowed the simultaneous targeting of a fluorescent tag and biotin label to the same antigenic site. Briefly, one of two antigenic sites typically co-localized in damaged axonal segments was visualized by the application of a fluorescent secondary antibody, with the other tagged via a biotinylated antibody. Next, an ABC kit was used, followed by the simultaneous application of fluorophore-tyramide and biotin-tyramide. After temporary mounting for fluorescent digital photomicroscopy, sections were incubated in ABC and reacted with diaminobenzidine before EM analysis. Double-labeling fluorescent immunocytochemistry with TSA clearly delineated damaged axonal segments. In addition, these same axonal segments yielded high-quality EM images with discrete electron-dense reaction products, thereby providing a simple and reproducible means for following fluorescent analysis with EM.
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| 5. |
- Büki, Andras, 1966-, et al.
(author)
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Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumatically induced axonal injury
- 2003
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 20:3, s. 261-268
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Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) evokes diffuse (traumatic) axonal injury (TAI), which contributes to morbidity and mortality. Damaged axons display progressive alterations gradually evolving to axonal disconnection. In severe TAI, the tensile forces of injury lead to a focal influx of Ca2+, initiating a series of proteolytic processes wherein the cysteine proteases, calpain and caspase modify the axonal cytoskeleton, causing irreversible damage over time postinjury. Although several studies have demonstrated that the systemic administration of calpain inhibitors reduces the extent of ischemic and traumatic contusional injury a direct beneficial effect on TAI has not been established to date. The current study was initiated to address this issue in an impact acceleration rat-TBI model in order to provide further evidence on the contribution of calpain-mediated proteolytic processes in the pathogenesis of TAI, while further supporting the utility of calpain-inhibitors. A single tail vein bolus injection of 30 mg/kg MDL-28170 was administered to Wistar rats 30 min preinjury. After injury the rats were allowed to survive 120 min when they were perfused with aldehydes. Brains were processed for immunohistochemical localization of damaged axonal profiles displaying either amyloid precursor protein (APP)- or RMO-14-immunoreactivity (IR), both considered markers of specific features of TAI. Digital data acquisition and statistical analysis demonstrated that preinjury administration of MDL-28170 significantly reduced the mean number of damaged RMO-14- as well as APP-IR axonal profiles in the brainstem fiber tracts analyzed. These results further underscore the role of calpain-mediated proteolytic processes in the pathogenesis of DAI and support the potential use of cell permeable calpain-inhibitors as a rational therapeutic approach in TBI.
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| 6. |
- Farkas, Orsolya, et al.
(author)
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Effects of pituitary adenylate cyclase activating polypeptide in a rat model of traumatic brain injury
- 2004
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In: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 123:1-3, s. 69-75
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Journal article (peer-reviewed)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has numerous different actions. Recent studies have shown that PACAP exerts neuroprotective effects not only in vitro but also in vivo, in animal models of global and focal cerebral ischemia, Parkinson's disease and axonal injuries. Traumatic brain injury has an increasing mortality and morbidity and it evokes diffuse axonal injury which further contributes to its damaging effects. The aim of the present study was to examine the possible neuroprotective effect of PACAP in a rat model of diffuse axonal injury induced by impact acceleration. Axonal damage was assessed by immunohistochemistry using an antiserum against beta-amyloid precursor protein, a marker of altered axoplasmic transport considered as key feature in axonal injury. In these experiments, we have established the dose response curves for PACAP administration in traumatic axonal injury, demonstrating that a single post-injury intracerebroventricular injection of 100 microg PACAP significantly reduced the density of damaged, beta-amyloid precursor protein-immunoreactive axons in the corticospinal tract.
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| 7. |
- Sándor, János, et al.
(author)
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A subduralis vérzés miatt kezelt betegek halálozását befolyásoló tényezók : [Predictors of lethal outcome in subdural haemorrhage]
- 2003
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In: Ideggyogyaszati Szemle. - : Literatura Medica Kiado. - 0019-1442 .- 2498-6208. ; 56:11-12, s. 386-395
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Journal article (peer-reviewed)abstract
- Background: Subdural haemorrhage (SDH) is of high public health importance because of its frequency, high case fatality ratio (CFR) and the young age of affected population. Despite the fact that the effectivity of guideline based treatment has been improved in the last decade, the Hungarian praxis shows variable compliance for recommendations.Objectives: The study aimed to describe the heterogeneity of the treatment effectivity (by geographically identifying the populations provided with appropriate or non-optimal level care), to determine the relationship between the institutional proxies quality and the results of treatment for SDH by linking the proxies properties to the patients' records.Methods: The institutions' protocols were assessed by a self-completed questionnaire in 1997. The participating hospitals treated 79% of the Hungarian patients with SDH. The Hungarian hospital discharge data in 1997-1999 were the source of patient specific data. The risk factors of lethal outcome were investigated by logistic regression analysis.Results: High proportion of patients had been treated in hospital with low compliance for guidelines. The non-permanent access to neurosurgical service and CT facility, the lack of intracranial pressure monitoring and the respiration support provided out of intensive care units worsened the survival of subjects. It was quantified that the full compliance could have diminished the case fatality ratio by 15-20%. The ratio of extreme county level CFRs exceeded 2.36 and extrapolating the effectivity observed in the county with lowest lethality, the Hungarian CFR would have been reduced by 21% among patients with SDH main diagnosis. (The interpretation of findings is limited by the lack of differentiation between acute and chronic cases and of direct categorisation of severity for subdural haemorrhage in the official hospital discharge records).Discussion: The study results urge the increase of compliance for evidence based guidelines, since despite of some validity issues, it was demonstrated that the deviation from recommended practice is reflected in the disadvantageous outcome.
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