| 1. |
- Büki, Andras, 1966-, et al.
(författare)
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Clinical and model research of neurotrauma
- 2009
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. ; 566, s. 41-55
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Tidskriftsartikel (refereegranskat)abstract
- Modeling traumatic brain injury represents a major challenge for neuroscientists - to represent extremely complex pathobiological processes kept under close surveillance in the most complex organ of a laboratory animal. To ensure that such models also reflect those alterations evoked by and/or associated with traumatic brain injury (TBI) in man, well-defined, graded, simple injury paradigms should be used with clear endpoints that also enable us to assess the relevance of our findings to human observations. It is of particular importance that our endpoints should harbor clinical significance, and to this end, biological markers ultimately associated with the pathological processes operant in TBI are considered the best candidate. This chapter provides protocols for relevant experimental models of TBI and clinical materials for neuroproteomic analysis.
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| 2. |
- Czeiter, Endre, et al.
(författare)
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Calpain inhibition reduces axolemmal leakage in traumatic axonal injury
- 2009
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 14:12, s. 5115-5123
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Tidskriftsartikel (refereegranskat)abstract
- Calcium-induced, calpain-mediated proteolysis (CMSP) has recently been implicated to the pathogenesis of diffuse (traumatic) axonal injury (TAI). Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP) alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA) and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA) was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor) or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.
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| 3. |
- 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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| 4. |
- Kövesdi, Erzsébet, et al.
(författare)
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Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats
- 2008
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Ingår i: Neurotoxicity research. - : Springer. - 1029-8428 .- 1476-3524. ; 13:2, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- Several in vitro and in vivo experiments have demonstrated the neuroprotective effects of pituitary adenylate cyclase activating polypeptide (PACAP) in focal cerebral ischemia, Parkinson's disease and traumatic brain injury (TBI). The aim of the present study was to analyze the effect of PACAP administration on diffuse axonal injury (DAI), an important contributor to morbidity and mortality associated with TBI, in a central fluid percussion (CFP) model of TBI. Rats were subjected to moderate (2 Atm) CFP injury. Thirty min after injury, 100 mu g PACAP was administered intracerebroventricularly. DAI was assessed by immunohistochemical detection of beta-amyloid precursor protein, indicating impaired axoplasmic transport, and RMO-14 antibody, representing foci of cytoskeletal alterations (neurofilament compaction), both considered classical markers of axonal damage. Analysis of damaged, immunoreactive axonal profiles revealed significant axonal protection in the PACAP-treated versus vehicle-treated animals in the corticospinal tract, as far as traumatically induced disturbance of axoplasmic transport and cytoskeletal alteration were considered. Similarly to our former observations in an impact acceleration model of diffuse TBI, the present study demonstrated that PACAP also inhibits DAI in the CFP injury model. The finding indicates that PACAP and derivates can be considered potential candidates for further experimental studies, or purportedly for clinical trials in the therapy of TBI.
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| 5. |
- Lückl, Jááos, et al.
(författare)
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Protein biomarkerek szerepe a koponyasérüles kísérletes modelljeiben és a klinikumban : [Protein biomarkers in experimental models and in clinical care of traumatic brain injury]
- 2007
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Ingår i: Ideggyogyaszati Szemle. - : Literatura Medica Kiado. - 0019-1442 .- 2498-6208. ; 60:7-8, s. 284-294
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury is the leading cause of mortality in Hungary in the population under 40 years of age. In Western societies, like the United Sates, traumatic brain injury represents an extreme social-economic burden, expected to become the third leading cause of mortality until 2020. Despite its' epidemiological significance, experimental therapeutic modalities developed in the last few decades did not prove efficient in the clinical care of severe traumatic brain injury. The reason for such a lack of success in terms of translating experimental results to clinical treatment at least partially could be explained by the paucity and the low sensitivity and specificity of clinical parameters endowing us to monitor the efficacy of the therapy. The drive for finding clinical parameters and monitoring tools that enable us to monitor treatment efficacy as well as outcome focused recent attention on biomarkers (and) surrogate markers that are based on rational pathological processes associated with/operant in traumatic brain injury. This review summarizes those biomarkers that could purportedly be used to monitor the treatment of the severely head injured while also providing information on salvageability facilitating the conduction of more rationally designed clinical studies.
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| 6. |
- Tamás, Andrea, et al.
(författare)
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Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats
- 2006
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 23:5, s. 686-695
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system. Numerous studies have shown its neuroprotective effects both in vitro and in vivo. Previously, it has been demonstrated that PACAP reduces brain damage in rat models of global and focal cerebral ischemia. Based on the protective effects of PACAP in cerebral ischemia and the presence of common pathogenic mechanisms in cerebral ischemia and traumatic brain injury (TBI), the aim of the present study was to investigate the possible protective effect of PACAP administered 30 min or 1 h postinjury in a rat model of diffuse axonal injury. Adult Wistar male rats were subjected to impact acceleration, and PACAP was administered intracerebroventricularly 30 min (n = 4), and 1 h after the injury (n = 5). Control animals received the same volume of vehicle at both time-points (n = 5). Two hours after the injury, brains were processed for immunohistochemical localization of damaged axonal profiles displaying either beta-amyloid precursor protein (beta-APP) or RMO-14 immunoreactivity, both considered markers of specific features of traumatic axonal injury. Our results show that treatment with PACAP (100 microg) 30 min or 1 h after the induction of TBI resulted in a significant reduction of the density of beta-APP-immunopositive axon profiles in the corticospinal tract (CSpT). There was no significant difference between the density of beta-APP-immunopositive axons in the medial longitudinal fascicle (MLF). PACAP treatment did not result in significantly different number of RMO-14-immunopositive axonal profiles in either brain areas 2 hours post-injury compared to normal animals. While the results of this study highlighted the complexity of the pathogenesis and manifestation of diffuse axonal injury, they also indicate that PACAP should be considered a potential therapeutic agent in TBI.
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