| 1. |
- Czigler, Andras, et al.
(författare)
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Hypertension exacerbates cerebrovascular oxidative stress induced by mild traumatic brain injury : Protective effects of the Mitochondria-Targeted Antioxidative Peptide SS-31
- 2019
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 36:23, s. 3309-3315
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) induces cerebrovascular oxidative stress, which is associated with neurovascular uncoupling, autoregulatory dysfunction, and persisting cognitive decline in both pre-clinical models and patients. However, single mild TBI (mTBI), the most frequent form of brain trauma, increases cerebral generation of reactive oxygen species (ROS) only transiently. We hypothesized that comorbid conditions might exacerbate long-term ROS generation in cerebral arteries after mTBI. Because hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive and spontaneously hypertensive rats (SHR) and assessed changes in cytoplasmic and mitochondrial superoxide (O2-) production by confocal microscopy in isolated middle cerebral arteries (MCA) 2 weeks after mTBI using dihydroethidine (DHE) and the mitochondria-targeted redox-sensitive fluorescent indicator dye MitoSox. We found that mTBI induced a significant increase in long-term cytoplasmic and mitochondrial O2- production in MCAs of SHRs and increased expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit Nox4, which were reversed to the normal level by treating the animals with the cell-permeable, mitochondria-targeted antioxidant peptide SS-31 (5.7 mg kg-1 day-1, i.p.). Persistent mTBI-induced oxidative stress in MCAs of SHRs was significantly decreased by inhibiting vascular NADPH oxidase (apocyinin). We propose that hypertension- and mTBI-induced cerebrovascular oxidative stress likely lead to persistent dysregulation of cerebral blood flow (CBF) and cognitive dysfunction, which might be reversed by SS-31 treatment.
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| 2. |
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| 3. |
- Nemes, Orsolya, et al.
(författare)
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Predictors of post-traumatic pituitary failure during long-term follow-up
- 2015
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Ingår i: Hormones - journal of endocrinology and metabolism. - : Hellenic Endocrine Society. - 1109-3099. ; 14:3, s. 383-391
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is increasing awareness among physicians of the risks of traumatic brain injury (TBI)-induced hypopituitarism. We have assessed the prevalence and risk factors of post-traumatic hypopituitarism by analyzing the TBI database of the University of Pecs.DESIGN: This consecutive analysis of 126 TBI survivors (mean age: 42.4 years, average follow-up time: 48 months) revealed that 60.3% had severe and 39.7% moderately severe trauma based on GCS score. Subdural hemorrhage (29.3%) and diffuse injury (27%) were the most common types of injury; 17.5% of patients suffered basal skull fractures.RESULTS: The prevalence of major anterior pituitary failure was 57.1%. Occurrence of total and partial growth hormone deficiency (GHD/GHI) was 39.7%, while LH/FSH, TSH and ACTH deficiencies were less frequent, namely 23.0%, 16.7% and 10.3%, respectively. Of the 82 patients with multiple endocrine evaluations, 31.7% presented significant changes in hormonal deficiencies during the follow-up period: new hormone deficiencies developed in 16 patients, while hormonal disturbances resolved in 10 subjects. Looking for factors influencing the prevalence of pituitary dysfunction, endocrine results were analyzed in relation to age, gender, GCS scores, injury types, basal skull fracture, ventricular drain insertion and necessity of neurosurgical intervention. All hormonal disturbances were more prevalent after severe trauma (OR: 3.25, p=0.002), while the need for surgery proved to be an independent determinant of multiple and GH deficits (OR: 3.72 (p=0.004) and 9.33 (p=0.001)).CONCLUSION: Post-traumatic hypopituitarism is common and may evolve or resolve over time. Victims of severe TBI and/or patients who have undergone neurosurgical intervention for head injury are the most prone to post-traumatic hypopituitarism.
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| 4. |
- Sorinola, Abayomi, et al.
(författare)
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Effectiveness of Traumatic Brain Injury Management Guideline Introduction in Hungary
- 2018
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Ingår i: Turkish Neurosurgery. - : Turkish Neurosurgi[c]al Society. - 1019-5149. ; 28:3, s. 410-415
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe the impact of the Traumatic Brain Injury management guideline introduction in Hungary. MATERIAL and METHODS: Hospital discharge records (HDR) including age, gender, codes of interventions applied, ICD codes of diagnosed disorders of patients admitted between 01/01/2004 and 31/12/2010 with the diagnosis of intracranial injury (S06 by ICD10) from every inpatient institution in Hungary were collected from the database of National Health Insurance Fund (NHIF). The Case Fatality Ratios (CFR) for one week, one month and six months were calculated for the periods before and after the guideline introduction. The change of CFRs was applied as indicators for change of clinical quality elicited by the guideline.RESULTS: The centers together at one week, one month and six months had pre-guideline introduction CFRs of 23.4%, 37.7% and 47.5% and post-guideline introduction CFRs of 22.1%, 39.1%, and 50.0% respectively. The secondary institutions together at one week, one month and six months had pre-guideline introduction CFRs of 21.5%, 34.8% and 46.3% and post-guideline introduction CFRs of 21.9%, 37.0%, and 48.9% respectively. None of the CFRs showed significant change.CONCLUSION: The effectiveness of TBI management guideline adaptation in Hungary is poor. Without supportive financing and external auditing system, guideline introduction alone cannot achieve standard clinical practice and a reduction in CFR.
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| 5. |
- Sorinola, Abayomi, et al.
(författare)
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Risk Factors of External Ventricular Drain Infection : Proposing a Model for Future Studies
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Background: External ventricular drain (EVD) has a major role in the management and monitoring of intracranial pressure (ICP) and its major complication is EVD infection. The risk factors for EVD infection are still a major topic of controversy, hence the need for further research.Objective: The objective of this review was to identify risk factors that affect the incidence of EVD infection and create a model, which can be used in future studies in order to contribute to elaborations on guideline for EVD.Methods: A PubMed and Google Scholar literature search was performed and data were extracted from studies published from 1966 through 2017. The search of the databases generated 604 articles and 28 articles of these were found to be relevant. A manual search of the 28 relevant papers generated 4 new articles. Of the 32 relevant articles, 20 articles that performed a multivariate analysis of the suspected risk factors of EVD infection and had a positive culture as a mandatory component in diagnosis were selected for data collection and analysis.Results: Because reviewed papers investigated only a few influencing factors, and could not determine convincingly the real risk factors of EVD infection and their real strengths. A total of 15 supposed influencing factors which includes: age, age & sex interactions, coinfection, catheter insertion outside the hospital, catheter type, CSF leakage, CSF sampling frequency, diagnosis, duration of catheterization, ICP > 20 mmHg, irrigation, multiple catheter, neurosurgical operation, reduced CSF glucose at catheter insertion and sex were identified.Conclusion: This review summarizes a set of variables which have to be covered by future clinical epidemiological investigations in order to describe the etiological background of EVD infection.
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| 6. |
- Szarka, Nikolett, et al.
(författare)
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Hypertension-Induced Enhanced Myogenic Constriction of Cerebral Arteries Is Preserved after Traumatic Brain Injury
- 2017
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 34:14, s. 2315-2319
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) was shown to impair pressure-induced myogenic response of cerebral arteries, which is associated with vascular and neural dysfunction and increased mortality of TBI patients. Hypertension was shown to enhance myogenic tone of cerebral arteries via increased vascular production of 20-hydroxyeicosatrienoic acid (HETE). This adaptive mechanism protects brain tissue from pressure/volume overload; however, it can also lead to increased susceptibility to cerebral ischemia. Although both effects may potentiate the detrimental vascular consequences of TBI, it is not known how hypertension modulates the effect of TBI on myogenic responses of cerebral vessels. We hypothesized that in hypertensive rats, the enhanced myogenic cerebrovascular response is preserved after TBI. Therefore, we investigated the myogenic responses of isolated middle cerebral arteries (MCA) of normotensive and spontaneously hypertensive rats (SHR) after severe impact acceleration diffuse brain injury. TBI diminished myogenic constriction of MCAs isolated from normotensive rats, whereas the 20-HETE-mediated enhanced myogenic response of MCAs isolated from SHRs was not affected by TBI. These results suggest that the optimal cerebral perfusion pressure values and vascular signaling pathways can be different and, therefore, should be targeted differently in normotensive and hypertensive patients following TBI.
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| 7. |
- Szarka, Nikolett, et al.
(författare)
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Single mild traumatic brain injury induces persistent disruption of the blood-brain barrier, neuroinflammation and ognitive decline in hypertensive rats
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 20:13, s. 3223-3223
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) induces blood-brain barrier (BBB) disruption, which contributes to secondary injury of brain tissue and development of chronic cognitive decline. However, single mild (m)TBI, the most frequent form of brain trauma disrupts the BBB only transiently. We hypothesized, that co-morbid conditions exacerbate persistent BBB disruption after mTBI leading to long term cognitive dysfunction. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive Wistar and spontaneously hypertensive rats (SHR) and we assessed BBB permeability, extravasation of blood-borne substances, neuroinflammation and cognitive function two weeks after trauma. We found that mTBI induced a significant BBB disruption two weeks after trauma in SHRs but not in normotensive Wistar rats, which was associated with a significant accumulation of fibrin and increased neuronal expression of inflammatory cytokines TNFα, IL-1β and IL-6 in the cortex and hippocampus. SHRs showed impaired learning and memory two weeks after mild TBI, whereas cognitive function of normotensive Wistar rats remained intact. Future studies should establish the mechanisms through which hypertension and mild TBI interact to promote persistent BBB disruption, neuroinflammation and cognitive decline to provide neuroprotection and improve cognitive function in patients with mTBI.
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| 8. |
- Szarka, Nikolett, et al.
(författare)
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Traumatic brain injury impairs myogenic constriction of cerebral arteries : role of mitochondria-derived H2O2 and TRPV4-dependent activation of BKca Channels
- 2018
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:7, s. 930-939
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) impairs autoregulation of cerebral blood flow, which contributes to the development of secondary brain injury, increasing mortality of patients. Impairment of pressure-induced myogenic constriction of cerebral arteries plays a critical role in autoregulatory dysfunction; however, the underlying cellular and molecular mechanisms are not well understood. To determine the role of mitochondria-derived H2O2 and large-conductance calcium-activated potassium channels (BKCa) in myogenic autoregulatory dysfunction, middle cerebral arteries (MCAs) were isolated from rats with severe weight drop-impact acceleration brain injury. We found that 24 h post-TBI MCAs exhibited impaired myogenic constriction, which was restored by treatment with a mitochondria-targeted antioxidant (mitoTEMPO), by scavenging of H2O2 (polyethylene glycol [PEG]-catalase) and by blocking both BKCa channels (paxilline) and transient receptor potential cation channel subfamily V member 4 (TRPV4) channels (HC 067047). Further, exogenous administration of H2O2 elicited significant dilation of MCAs, which was inhibited by blocking either BKCa or TRPV4 channels. Vasodilation induced by the TRPV4 agonist GSK1016790A was inhibited by paxilline. In cultured vascular smooth muscle cells H2O2 activated BKCa currents, which were inhibited by blockade of TRPV4 channels. Collectively, our results suggest that after TBI, excessive mitochondria-derived H2O2 activates BKCa channels via a TRPV4-dependent pathway in the vascular smooth muscle cells, which impairs pressure-induced constriction of cerebral arteries. Future studies should elucidate the therapeutic potential of pharmacological targeting of this pathway in TBI, to restore autoregulatory function in order to prevent secondary brain damage and decrease mortality.
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| 9. |
- Tamás, Viktória, et al.
(författare)
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The Young Male Syndrome : An Analysis of Sex, Age, Risk Taking and Mortality in Patients With Severe Traumatic Brain Injuries
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 10:366
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Tidskriftsartikel (refereegranskat)abstract
- Higher risk taking is particularly characteristic for males between 15 and 35 years, the age when intrasexual competition is the strongest. This fitness-maximizing strategy, however, also has negative consequences; previous data revealed that males have a significantly higher tendency to die in accidents. This retrospective study aimed to assess whether age-related risk taking, often associated with the reproductive competition between males, and referred to as the Young Male Syndrome (YMS), may play a role in the high incidence of severe traumatic brain injury (sTBI) in young males. Derived from the available evidence and the main assumptions of the YMS, we expected that men, especially when they are in the age when their reproductive potential peaks, are more likely to suffer sTBI from highly risky behaviors that also lead to higher mortality. It was also expected that alcohol intoxication makes the demographic pattern of sTBI even more similar to what previous research on the YMS implies. We analyzed demographic data of patients with sTBI (N = 365) registered in a clinical database. To this end, we built Generalized Linear Mixed Models (GLMM) to reveal which of the demographic characteristics are the best predictors for risky behaviors leading to sTBI and death as a consequence of the injury. The data suggest that younger people acquired sTBI from riskier behaviors compared to members of older age groups, irrespective of their sex. Moreover, being male and being alcohol intoxicated also contributed significantly to risk-taking behavior. Mortality rate after the injury, however, increased with the age of the patient and did not depend on the riskiness of the behavior. The results indicate that the demographic distribution of the specific patient population in our focus cannot be simply explained by the YMS. However, higher incidence rates of males among the patients are in line with the core assumptions of the YMS. These data indicate that epidemiological studies should also take into consideration evolutionary theories and highlight the importance of age and sex specific prevention strategies.
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| 10. |
- Tóth, Arnold, et al.
(författare)
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Cerebral Microbleeds Temporarily Become Less Visible or Invisible in Acute Susceptibility Weighted Magnetic Resonance Imaging : A Rat Study
- 2019
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 36:10, s. 1670-1677
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported human traumatic brain injury cases demonstrating acute to subacute microbleed appearance changes in susceptibility-weighted imaging (SWI-magnetic resonance imaging [MRI]). This study aims to confirm and characterize such temporal microbleed appearance alterations in an experimental model. To elicit microbleed formation, brains of male Sprague Dawley rats were pierced in a depth of 4 mm, in a parasagittal position bilaterally using 159 mu m and 474 mu m needles, without the injection of autologous blood or any agent. Rats underwent 4.7 T MRI immediately, then at multiple time points until 125 h. Volumes of hypointensities consistent with microbleeds in SWI were measured using an intensity threshold-based approach. Microbleed volumes across time points were compared using repeated measures analysis of variance. Microbleeds were assessed by Prussian blue histology at different time points. Hypointensity volumes referring to microbleeds were significantly decreased (corrected p < 0.05) at 24 h compared with the immediate or the 125 h time points. By visual inspection, microbleeds were similarly detectable at the immediate and 125 h imaging but were decreased in extent or completely absent at 24 h or 48 h. Histology confirmed the presence of microbleeds at all time points and in all animals. This study confirmed a general temporary reduction in visibility of microbleeds in the acute phase in SWI. Such short-term appearance dynamics of microbleeds should be considered when using SWI as a diagnostic tool for microbleeds in traumatic brain injury and various diseases.
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| 11. |
- Toth, Peter, et al.
(författare)
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Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling : Pathomechanisms, perspectives, and therapeutic implications
- 2016
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Ingår i: American Journal of Physiology. - : HighWire Press. - 0002-9513 .- 2163-5773. ; 311:5, s. H1118-H1131
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) is a major health problem worldwide. In addition to its high mortality (35-40%), survivors are left with cognitive, behavioral, and communicative disabilities. While little can be done to reverse initial primary brain damage caused by trauma, the secondary injury of cerebral tissue due to cerebro-microvascular alterations and dysregulation of cerebral blood flow (CBF) is potentially preventable. This review focuses on functional, cellular, and molecular changes of autoregulatory function of CBF (with special focus on cerebrovascular myogenic response) that occur in cerebral circulation after TBI and explores the links between autoregulatory dysfunction, impaired myogenic response, microvascular impairment, and the development of secondary brain damage. We further provide a synthesized translational view of molecular and cellular mechanisms involved in cortical spreading depolarization-related neurovascular dysfunction, which could be targeted for the prevention or amelioration of TBI-induced secondary brain damage.
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