| 7641. |
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| 7642. |
- Gabriel, J. P., et al.
(författare)
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Locomotor pattern in the adult zebrafish spinal cord in vitro
- 2008
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 99:1, s. 37-48
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Tidskriftsartikel (refereegranskat)abstract
- The zebrafish is an attractive model system for studying the function of the spinal locomotor network by combining electrophysiological, imaging, and genetic approaches. Thus far, most studies have been focusing on embryonic and larval stages. In this study we have developed an in vitro preparation of the isolated spinal cord from adult zebrafish in which locomotor activity can be induced while the activity of single neurons can be monitored using whole cell recording techniques. Application of NMDA elicited rhythmic locomotor activity that was monitored by recording from muscles or ventral roots in semi-intact or isolated spinal cord preparations, respectively. This rhythmic activity displayed a left-right alternation and a rostrocaudal delay. Blockade of glycinergic synaptic transmission by strychnine switched the alternating activity into synchronous bursting in the left and right sides as well as along the rostrocaudal axis. Whole cell recordings from motoneurons showed that they receive phasic synaptic inputs that were correlated with the locomotor activity recorded in ventral roots. This newly developed in vitro preparation of the adult zebrafish spinal cord will allow examination of the organization of the spinal locomotor network in an adult system to complement studies in zebrafish larvae and new born rodents.
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| 7643. |
- Gahm, Caroline, et al.
(författare)
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Reduced neuronal injury after treatment with NG-nitro-L-arginine methyl ester (L-NAME) or 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) following experimental brain contusion
- 2005
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 57:6, s. 1272-1281
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Nitric oxide (NO) and oxygen free radicals are implicated in the pathophysiology of traumatic brain injury (TBI). Peroxynitrite formation from NO and superoxide contributes to secondary neuronal injury but the neuroprotective effects of nitric oxide synthase (NOS)-inhibitors have been contradictory. This study was undertaken to examine whether PTtic administration of the (NOS)-inhibitor N-nitro-l-arginine methyl ester (L-NAME), and a combination of L-NAME and the nitrone radical scavenger 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) favorable affects neuronal injury in a model of TBI. METHODS: A weight-drop model of TBI was used. The animals received L-NAME, S-PBN or a combination of the drugs 15 minutes prothrombin time (PT) and sacrificed after 24 hours or six days. NOS activity was measured by the conversion of L-[U-C]arginine to L-[U-C]citrulline. Peroxynitrite formation, cellular apoptosis, neuronal degeneration and survival were assessed by nitrotyrosine-, TUNEL-, Fluoro-Jade- and NeuN-stainings. RESULTS: eNOS and nNOS activity was significantly reduced in animals that received L-NAME alone or the combination with S-PBN. iNOS activity or iNOS immunoreactivity was not affected. All treatments significantly reduced neuronal degeneration and nitrotyrosine immunoreactivity at 24 hours and increased neuronal survival at six days PT. No differences were detected between L-NAME and L-NAME + S-PBN groups. CONCLUSION: NO from NOS contributes to secondary neuronal injury in this TBI-model. PTtic treatment does not inhibit early beneficial NO-related effects. L-NAME and S-PBN limit peroxynitrite formation, promoting neuronal survival. The combination of L-NAME and S-PBN was neuroprotective; surprisingly no additive effects were found on nitrotyrosine formation, apoptosis or neuronal survival.
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| 7644. |
- Galanopoulou, Aristea S., et al.
(författare)
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Epilepsy therapy development: Technical and methodologic issues in studies with animal models
- 2013
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Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 54, s. 13-23
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Tidskriftsartikel (refereegranskat)abstract
- The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting practices that will enhance the uniformity, reliability, and reporting of early stage preclinical studies with animal seizure and epilepsy models that aim to develop and evaluate new therapies for seizures or epilepsies, using multidisciplinary approaches. The topics considered include the following: (1) implementation of better study design and reporting practices; (2) incorporation in the study design and analysis of covariants that may influence outcomes (including species, age, sex); (3) utilization of approaches to document target relevance, exposure, and engagement by the tested treatment; (4) utilization of clinically relevant treatment protocols; (5) optimization of the use of video-electroencephalography (EEG) recordings to best meet the study goals; and (6) inclusion of outcome measures that address the tolerability of the treatment or study end points apart from seizures. We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers.
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| 7645. |
- Galos, Peter, et al.
(författare)
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Capturing of intracranial pressure treatment during neurointensive care in patients with acute brain injury using a novel tablet-based method
- 2022
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Ingår i: Journal of clinical monitoring and computing. - : Springer Nature. - 1387-1307 .- 1573-2614. ; 36:6, s. 1731-1738
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Tidskriftsartikel (refereegranskat)abstract
- Critical care is complex and stressful. It is difficult to register in real time data not recorded by automatic systems. Time-specific knowledge of manual measures is important for understanding pathophysiology and for analyzing treatment and quality of care. Therefore, a novel iPad-based method for registration of manual measures was developed, which many can build themselves. Using a configuration for intracranial pressure (ICP) management, the methodology was validated, ICP treatment captured, and the quality of ICP management evaluated. Twenty-two patients with acute brain injuries were studied. The iPad-system was totally used for 2538 h. Thirteen-hundred-five manual measures were entered. Thirty-nine episodes of predefined ICP insults were identified. During 16/39 episodes, ICP treatments were registered. For 4/39 episodes treatments were registered within 90 s before or after the episode. For 3/39 episodes it was registered that treatment was intentionally refrained. In 15/16 episodes without registered treatment, the insult was mild or reasonable explanations were found when medical records and the Patient data management system were reviewed. In one situation without particular circumstances, morphine and clonidine were given to decrease ICP but not registered. No episodes of downtime or loss of data occurred. The developed methodology appears to be stable and robust as well as feasible and user-friendly. It was possible to capture the treatment of ICP insults with high temporal resolution, and to evaluate the quality of ICP management. An own developed novel tablet-based system like our system may be a promising potential tool useful in various future intensive care applications.
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| 7646. |
- Galovic, Marian, et al.
(författare)
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Seizures and Epilepsy After Stroke: Epidemiology, Biomarkers and Management.
- 2021
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Ingår i: Drugs & aging. - : Springer Science and Business Media LLC. - 1179-1969 .- 1170-229X. ; 38, s. 285-299
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Forskningsöversikt (refereegranskat)abstract
- Stroke is the leading cause of seizures and epilepsy in older adults. Patients who have larger and more severe strokes involving the cortex, are younger, and have acute symptomatic seizures and intracerebral haemorrhage are at highest risk of developing post-stroke epilepsy. Prognostic models, including the SeLECT and CAVE scores, help gauge the risk of epileptogenesis. Early electroencephalogram and blood-based biomarkers can provide information additional to the clinical risk factors of post-stroke epilepsy. The management of acute versus remote symptomatic seizures after stroke is markedly different. The choice of an ideal antiseizure medication should not only rely on efficacy but also consider adverse effects, altered pharmacodynamics in older adults, and the influence on the underlying vascular co-morbidity. Drug-drug interactions, particularly those between antiseizure medications and anticoagulants or antiplatelets, also influence treatment decisions. In this review, we describe the epidemiology, risk factors, biomarkers, and management of seizures after an ischaemic or haemorrhagic stroke. We discuss the special considerations required for the treatment of post-stroke epilepsy due to the age, co-morbidities, co-medication, and vulnerability of stroke survivors.
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| 7647. |
- Gameiro, Joana, et al.
(författare)
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Prognosis of cerebral vein thrombosis presenting as isolated headache: Early vs. late diagnosis
- 2012
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 32:5, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyse the outcome of cerebral venous thrombosis (CVT) patients presenting with isolated headache, specifically to compare isolated headache patients with early vs. late CVT diagnosis. Method: In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) database we compared the outcome of patients with isolated headache and a CVT diagnosed early (<= 7 days from onset) vs. late (> 7 days). We retrieved 100 patients with isolated headache, 52 patients with early CVT diagnosis (early isolated headache) and 48 with late CVT diagnosis (late isolated headache). Results: Neurological worsening was more frequent within early isolated headache patients (23% vs. 8%) (p = 0.045). At the last follow-up (median 411 days), 93% patients had a complete recovery, and 4% were dead or dependent, with no significant difference between early isolated headache and late isolated headache. Conclusion: The outcome of CVT patients with isolated headache diagnosed early or late was similarly favourable, but there was a higher proportion of neurological worsening in the acute phase among early isolated headache patients, who need close neurological monitoring.
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| 7648. |
- Ganesalingam, Jeban, et al.
(författare)
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pNfH is a promising biomarker for ALS
- 2013
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Ingår i: Amytrophic Lateral Sclerosis and Frontotemporal degeneration. - : Informa Healthcare. - 2167-8421 .- 2167-9223. ; 14:2, s. 146-149
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Tidskriftsartikel (refereegranskat)abstract
- A diagnostic biomarker for ALS would permit early intervention with disease-modifying therapies while a biomarker for disease activity could accelerate the pace of drug discovery by facilitating shorter, and less costly, drug trials to be conducted with a smaller number of patients. Neurofilaments are the most abundant neuronal cytoskeletal protein. We set out to determine whether pNfH was a credible biomarker for ALS. pNfH levels were determined using an ELISA for 150 ALS subjects and 140 controls. We demonstrated a seven-fold elevation in the cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy subunit (pNfH) in ALS (median n = 2787 pg/ml, n = 150), compared to headache and other benign controls (3 (4 pg/ml, n = 100, p = < 0.05). There was a 10-fold elevation of pNfH compared to ALS mimics (266 pg/ml, n = 20) and other neurodegenerative and inflammatory conditions (27 (pg/ml for n = 20) which was also highly significant (p = < 0.05). pNfH achieved a diagnostic sensitivity of 90% and specificity of 87% in distinguishing ALS from all controls. We also detected an inverse correlation between CSF pNfH levels and disease duration (time from symptom onset to death, r(2) = 0.1247, p = 0.001). In conclusion, pNfH represents a promising candidate for inclusion in a panel of diagnostic and prognostic biomarkers.
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| 7649. |
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| 7650. |
- Garcia, Maria João, et al.
(författare)
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Prognostic and Predictive Factors in Early Alzheimer's Disease : A Systematic Review
- 2024
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Ingår i: Journal of Alzheimer's Disease Reports. - 2542-4823. ; 8:1, s. 203-240
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Forskningsöversikt (refereegranskat)abstract
- Background: Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia. Objective: To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments. Methods: Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected. Results: Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. APOE4 may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression. Conclusions: Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. APOE4 predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.
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