| 1. |
- 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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| 2. |
- 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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| 3. |
- Bukovics, Peter, et al.
(författare)
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Changes of PACAP level in cerebrospinal fluid and plasma of patients with severe traumatic brain injury
- 2014
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 60, s. 18-22
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Tidskriftsartikel (refereegranskat)abstract
- PACAP has well-known neuroprotective potential including traumatic brain injury (TBI). Its level is up-regulated following various insults of the CNS in animal models. A few studies have documented alterations of PACAP levels in human serum. The time course of post-ictal PACAP levels, for example, show correlation with migraine severity. Very little is known about the course of PACAP levels following CNS injury in humans and the presence of PACAP has not yet been detected in cerebrospinal fluid (CSF) of subjects with severe TBI (sTBI). The aim of the present study was to determine whether PACAP occurs in the CSF and plasma (Pl) of patients that suffered sTBI and to establish a time course of PACAP levels in the CSF and Pl. Thirty eight subjects with sTBI were enrolled with a Glasgow Coma Scale ≤8 on admission. Samples were taken daily, until the time of death or for maximum 10 days. Our results demonstrated that PACAP was detectable in the CSF, with higher concentrations in patients with TBI. PACAP concentrations markedly increased in both Pl and CSF in the majority of patients 24-48h after the injury stayed high thereafter. In cases of surviving patients, Pl and CSF levels displayed parallel patterns, which may imply the damage of the blood-brain barrier. However, in patients, who died within the first week, Pl levels were markedly higher than CSF levels, possibly indicating the prognostic value of high Pl PACAP levels.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Czobor, Pal, et al.
(författare)
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The European Adolescent Assessment Dialogue (EuroADAD) : A Psychometric Evaluation
- 2011
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Ingår i: European Addiction Research. - : S. Karger AG. - 1022-6877 .- 1421-9891. ; 17:6, s. 302-315
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Adolescent Drug Abuse Diagnosis (ADAD) has been a gold standard for assessing drug use and associated problems in adolescents. Criticism of the instrument has been increasing. A new instrument, the European Adolescent Assessment Dialogue (EuroADAD) that builds on ADAD's strengths but seeks to address its limitations is now available, but has not been subjected to comprehensive psychometric evaluation. Objective: To examine the psychometric properties of the EuroADAD across various settings in adolescent populations who developed or were at a high risk of developing substance use and psychosocial adaptation problems. Participants and Settings: Three of the samples were collected in Hungary, including: institutionalized youths from juvenile residential facility (n = 295); adolescents from outpatient psychiatry facility (n = 278), and controls (n = 59). An additional sample was collected in the Netherlands, and consisted of adolescent boys from an independent residential institution for youth with severe behavioral problems (n = 51). Procedure: The EuroADAD was administered by trained interviewers. Data were collected through face-to-face interviews and self-report questionnaires. Results: Reliability: the intraclass correlation was high for all domains of the EuroADAD; reliability analyses indicated good test-retest reliability, and internal consistency. Validity: difference among study samples was significant (p < 0.05) for the majority of the domains, with juvenile institution and psychiatric outpatient subjects exhibiting higher severity in most areas compared to controls. The Hungarian and Dutch samples were comparable, expect for the legal domain, due to the higher severity of behavioral problems in the Dutch sample. Several domains of the instrument, including 'alcohol', 'drugs' and 'legal' showed an association with trait aggression as measured by the Buss-Perry Aggression Questionnaire and with Novelty Seeking on the Cloninger Temperament and Character Inventory. Conclusion: Based on the pattern and significance of group differences, and correlations with other measures, the scale has good criterion, and convergent and discriminant construct validity. The EuroADAD is a reliable and valid tool for the assessment of alcohol and drug use, and related psychosocial problems in adolescents.
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| 7. |
- Farkas, Orsolya, et al.
(författare)
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Effects of pituitary adenylate cyclase activating polypeptide in a rat model of traumatic brain injury
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 123:1-3, s. 69-75
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Tidskriftsartikel (refereegranskat)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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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