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Article: Editorial: Global excellence in cellular neuropathology: Europe.

Pluta, Ryszard / Popa-Wagner, Aurel / Hermann, Dirk M

2023 Volume 17, Page(s) 1289444

Language	English
Publishing date	2023-10-25
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2023.1289444
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Article: Stem Cell Treatments in Preclinical Relevant Stroke Models.

Pinosanu, Leonard Radu / Wolff, Nora / Olaru, Denissa Greta / Popa-Wagner, Aurel

Current health sciences journal

2023 Volume 49, Issue 4, Page(s) 487–494

Abstract: Since stroke has limited treatment options, an active search for new therapeutic approaches is required. Initial excitement of using cell-based therapies to stimulate recovery processes in the ischemic brain turned into a more measured perspective, ... ...

Abstract	Since stroke has limited treatment options, an active search for new therapeutic approaches is required. Initial excitement of using cell-based therapies to stimulate recovery processes in the ischemic brain turned into a more measured perspective, acknowledging obstacles related to the unfavorable environments associated in part with aging. Given the predominance of stroke in older populations, evaluating the effectiveness of cell therapies in aged brain environments is essential and clinically relevant. Despite a common perception of the aged brain being resistant to regeneration, recent research with neural precursor cells and bone marrow-derived mesenchymal stem cells indicates that cell-based therapy can promote plasticity and remodeling in the aged rat brain. However, significant differences in the aged brain compared to the young brain, such as expedited progression of ischemic injury to brain infarction, decreased rate of endogenous neurogenesis, and delayed onset of neurological recovery, must be noted. The effectiveness of cell-based therapies may further be connected to age-related comorbidities such as diabetes or hyperlipidemia, potentially leading to maladaptive or impaired brain remodeling. These age-related factors need careful consideration in the clinical application of restorative therapies for stroke.
Language	English
Publishing date	2023-12-29
Publishing country	Romania
Document type	Journal Article ; Review
ZDB-ID	2708703-7
ISSN	2069-4032 ; 2067-0656
ISSN (online)	2069-4032
ISSN	2067-0656
DOI	10.12865/CHSJ.49.04.02
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Article ; Online: Beam narrowing test: a motor index of post-stroke motor evaluation in an aged rat model of cerebral ischemia.

Pinosanu, Leonard Radu / Boboc, Ianis Kevyn Stefan / Balseanu, Tudor Adrian / Gresita, Andrei / Hermann, Dirk M / Popa-Wagner, Aurel / Catalin, Bogdan

Journal of neural transmission (Vienna, Austria : 1996)

2024

Abstract: Each year, 15 million people worldwide suffer from strokes. Consequently, researchers face increasing pressure to develop reliable behavioural tests for assessing functional recovery after a stroke. Our aim was to establish a new motor performance index ... ...

Abstract	Each year, 15 million people worldwide suffer from strokes. Consequently, researchers face increasing pressure to develop reliable behavioural tests for assessing functional recovery after a stroke. Our aim was to establish a new motor performance index that can be used to evaluate post-stroke recovery in both young and aged animals. Furthermore, we validate the proposed procedure and recommend the necessary number of animals for experimental stroke studies. Young (n = 20) and aged (n = 27) Sprague-Dawley rats were randomly assigned to receive either sham or stroke surgery. The newly proposed performance index was calculated for the post-stroke acute, subacute and chronic phases. The advantage of using our test over current tests lies in the fact that the newly proposed motor index test evaluates not only the performance of the unaffected side in comparison to the affected one but also assesses overall performance by taking into account speed and coordination. Moreover, it reduces the number of animals needed to achieve a statistical power of 80%. This aspect is particularly crucial when studying aged rodents. Our approach can be used to monitor and assess the effectiveness of stroke therapies in experimental models using aged animals.
Language	English
Publishing date	2024-04-10
Publishing country	Austria
Document type	Journal Article
ZDB-ID	184163-4
ISSN	1435-1463 ; 0300-9564
ISSN (online)	1435-1463
ISSN	0300-9564
DOI	10.1007/s00702-024-02768-0
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Article ; Online: Pharmacological and stem cell therapy of stroke in animal models: Do they accurately reflect the response of humans?

Ruscu, Mihai / Glavan, Daniela / Surugiu, Roxana / Doeppner, Thorsten R / Hermann, Dirk M / Gresita, Andrei / Capitanescu, Bogdan / Popa-Wagner, Aurel

Experimental neurology

2024 Volume 376, Page(s) 114753

Abstract: Cerebrovascular diseases are the second leading cause of death worldwide. Despite significant research investment, the only available therapeutic options are mechanical thrombectomy and tissue plasminogen activator thrombolysis. None of the more than a ... ...

Abstract	Cerebrovascular diseases are the second leading cause of death worldwide. Despite significant research investment, the only available therapeutic options are mechanical thrombectomy and tissue plasminogen activator thrombolysis. None of the more than a thousand drugs tested on animal models have proven successful in human clinical trials. Several factors contribute to this poor translation of data from stroke-related animal models to human stroke patients. Firstly, our understanding of the molecular and cellular processes involved in recovering from an ischemic stroke is severely limited. Secondly, although the risk of stroke is particularly high among older patients with comorbidities, most drugs are tested on young, healthy animals in controlled laboratory conditions. Furthermore, in animal models, the tracking of post-stroke recovery typically spans only 3 to 28 days, with occasional extensions to 60 days, whereas human stroke recovery is a more extended and complex process. Thirdly, young animal models often exhibit a considerably higher rate of spontaneous recovery compared to humans following a stroke. Fourth, only a very limited number of animals are utilized for each condition, including control groups. Another contributing factor to the much smaller beneficial effects in humans is that positive outcomes from numerous animal studies are more readily accepted than results reported in human trials that do not show a clear benefit to the patient. Useful recommendations for conducting experiments in animal models, with increased chances of translatability to humans, have been issued by both the STEPS investigative team and the STAIR committee. However, largely, due to economic factors, these recommendations are largely ignored. Furthermore, one might attribute the overall failures in predicting and subsequently developing effective acute stroke therapies beyond thrombolysis to potential design deficiencies in clinical trials.
MeSH term(s)	Animals ; Humans ; Stroke/therapy ; Disease Models, Animal ; Stem Cell Transplantation/methods
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2024.114753
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Article: Epigenetics of Ageing and Psychiatric Disorders.

Colită, Cezar-Ivan / Udristoiu, Ion / Ancuta, Diana-Larisa / Hermann, Dirk M / Colita, Daniela / Colita, Eugen / Glavan, Daniela / Popa-Wagner, Aurel

Journal of integrative neuroscience

2024 Volume 23, Issue 1, Page(s) 13

Abstract: Both classic epigenetic modifications and microRNAs can impact a range of bodily processes, from metabolism to brain function, and may contribute to the development of diseases such as cancer, cardiovascular disorders, and psychiatric disorders. Numerous ...

Abstract	Both classic epigenetic modifications and microRNAs can impact a range of bodily processes, from metabolism to brain function, and may contribute to the development of diseases such as cancer, cardiovascular disorders, and psychiatric disorders. Numerous studies suggest a connection between epigenetic changes and mood disorders. In this study, we performed a comprehensive search using PubMed and Google for the terms "epigenetics", "ageing", "miRNA", "schizophrenia", and "mood disorders" in the titles and abstracts of articles. Epigenetic changes during early life may play a crucial role in triggering severe mental disorders and shaping their clinical trajectory. Although these alterations can take place at any age, their impact may not be immediately evident or observable until later in life. Epigenetic modifications play a crucial role in the ageing process and challenge the prevailing belief that mutations are the primary driver of ageing. However, it is plausible that these epigenetic changes are a consequence of the disorder rather than its root cause. Moreover, both the disorder and the epigenetic alterations may be influenced by shared environmental or genetic factors. In the near future, we might be able to replace chronological age with biological age, based on the epigenetic clock, with the promise of providing greater therapeutic benefits. A wide range of epigenetic drugs are currently under development at various stages. Although their full effectiveness is yet to be realized, they show great potential in the treatment of cancer, psychiatric disorders, and other complex diseases.
MeSH term(s)	Humans ; DNA Methylation ; Epigenesis, Genetic ; Mental Disorders/genetics ; Mental Disorders/drug therapy ; Schizophrenia ; MicroRNAs ; Aging/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2024-01-29
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2136427-8
ISSN	0219-6352
ISSN	0219-6352
DOI	10.31083/j.jin2301013
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Article ; Online: The post-stroke young adult brain has limited capacity to re-express the gene expression patterns seen during early postnatal brain development.

Ruscu, Mihai / Capitanescu, Bogdan / Rupek, Paul / Dandekar, Thomas / Radu, Eugen / Hermann, Dirk M / Popa-Wagner, Aurel

Brain pathology (Zurich, Switzerland)

2024 , Page(s) e13232

Abstract: The developmental origins of the brain's response to injury can play an important role in recovery after a brain lesion. In this study, we investigated whether the ischemic young adult brain can re-express brain plasticity genes that were active during ... ...

Abstract	The developmental origins of the brain's response to injury can play an important role in recovery after a brain lesion. In this study, we investigated whether the ischemic young adult brain can re-express brain plasticity genes that were active during early postnatal development. Differentially expressed genes in the cortex of juvenile post-natal day 3 and the peri-infarcted cortical areas of young, 3-month-old post-stroke rats were identified using fixed-effects modeling within an empirical Bayes framework through condition-specific comparison. To further analyze potential biological processes, upregulated and downregulated genes were assessed for enrichment using GSEA software. The genes showing the highest expression changes were subsequently verified through RT-PCR. Our findings indicate that the adult brain partially recapitulates the gene expression profile observed in the juvenile brain but fails to upregulate many genes and pathways necessary for brain plasticity. Of the upregulated genes in post-stroke brains, specific roles have not been assigned to Apobec1, Cenpf, Ect2, Folr2, Glipr1, Myo1f, and Pttg1. New genes that failed to upregulate in the adult post-stroke brain include Bex4, Cd24, Klhl1/Mrp2, Trim67, and St8sia2. Among the upregulated pathways, the largest change was observed in the KEGG pathway "One carbon pool of folate," which is necessary for cellular proliferation, followed by the KEGG pathway "Antifolate resistance," whose genes mainly encode the family of ABC transporters responsible for the efflux of drugs that have entered the brain. We also noted three less-described downregulated KEGG pathways in experimental models: glycolipid biosynthesis, oxytocin, and cortisol pathways, which could be relevant as therapeutic targets. The limited brain plasticity of the adult brain is illustrated through molecular and histological analysis of the axonal growth factor, KIF4. Collectively, these results strongly suggest that further research is needed to decipher the complex genetic mechanisms that prevent the re-expression of brain plasticity-associated genes in the adult brain.
Language	English
Publishing date	2024-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.13232
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Article ; Online: Die Rolle zirkadianer Rhythmik im Alter und bei ADHS – ein Überblick.

Popa-Wagner, A

Fortschritte der Neurologie-Psychiatrie

2016 Volume 84, Issue S 02, Page(s) S77–S79

Abstract: The circadian rhythms coordinates the internal physiology to increase the homeostatic capacity thereby providing both a survival advantage to the system and an optimization of energy budgeting. Because multiple-oscillator circadian mechanisms are likely ... ...

Title translation	The Role of Circadian Rhythms in Aging and ADHD.
Abstract	The circadian rhythms coordinates the internal physiology to increase the homeostatic capacity thereby providing both a survival advantage to the system and an optimization of energy budgeting. Because multiple-oscillator circadian mechanisms are likely to play a role in regulating human health, and may contribute to the aging process, we give an overview of the relationship between the central clock in the hypothalamus and peripheral clocks for psychological health and aging.
MeSH term(s)	Aging ; Attention Deficit Disorder with Hyperactivity/genetics ; Attention Deficit Disorder with Hyperactivity/physiopathology ; Attention Deficit Disorder with Hyperactivity/psychology ; Circadian Rhythm ; Circadian Rhythm Signaling Peptides and Proteins/genetics ; Humans
Chemical Substances	Circadian Rhythm Signaling Peptides and Proteins
Language	German
Publishing date	2016-10
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	625328-3
ISSN	1439-3522 ; 0720-4299
ISSN (online)	1439-3522
ISSN	0720-4299
DOI	10.1055/s-0042-113959
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Ui II Zs.110/X: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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Article: Editorial: Hot Topics in Cellular Neuropathology.

Hermann, Dirk M / Popa-Wagner, Aurel / Peruzzotti-Jametti, Luca / Gunzer, Matthias

Frontiers in cellular neuroscience

2022 Volume 16, Page(s) 895861

Language	English
Publishing date	2022-04-19
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.895861
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Article ; Online: Nanodrugs for the Treatment of Ischemic Stroke: A Systematic Review.

Ruscu, Mihai / Cercel, Andreea / Kilic, Ertugrul / Catalin, Bogdan / Gresita, Andrei / Hermann, Dirk M / Albu, Carmen Valeria / Popa-Wagner, Aurel

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Ischemic stroke, a significant neurovascular disorder, currently lacks effective restorative medication. However, recently developed nanomedicines bring renewed promise for alleviating ischemia's effects and facilitating the healing of neurological and ... ...

Abstract	Ischemic stroke, a significant neurovascular disorder, currently lacks effective restorative medication. However, recently developed nanomedicines bring renewed promise for alleviating ischemia's effects and facilitating the healing of neurological and physical functions. The aim of this systematic review was to evaluate the efficacy of nanotherapies in animal models of stroke and their potential impact on future stroke therapies. We also assessed the scientific quality of current research focused on nanoparticle-based treatments for ischemic stroke in animal models. We summarized the effectiveness of nanotherapies in these models, considering multiple factors such as their anti-inflammatory, antioxidant, and angiogenetic properties, as well as their safety and biodistribution. We conclude that the application of nanomedicines may reduce infarct size and improve neurological function post-stroke without causing significant organ toxicity.
MeSH term(s)	Animals ; Tissue Distribution ; Stroke/drug therapy ; Ischemic Stroke/drug therapy ; Anti-Inflammatory Agents ; Nanoparticles/therapeutic use ; Brain Ischemia/drug therapy
Chemical Substances	Anti-Inflammatory Agents
Language	English
Publishing date	2023-06-28
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310802
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Article: Clinical Ageing.

Surugiu, Roxana / Burdusel, Daiana / Ruscu, Mihai-Andrei / Cercel, Andreea / Hermann, Dirk M / Cadenas, Israel Fernandez / Popa-Wagner, Aurel

Sub-cellular biochemistry

2023 Volume 103, Page(s) 437–458

Abstract: Ageing is generally characterised by the declining ability to respond to stress, increasing homeostatic imbalance, and increased risk of ageing-associated diseases . Mechanistically, the lifelong accumulation of a wide range of molecular and cellular ... ...

Abstract	Ageing is generally characterised by the declining ability to respond to stress, increasing homeostatic imbalance, and increased risk of ageing-associated diseases . Mechanistically, the lifelong accumulation of a wide range of molecular and cellular impairments leads to organismal senescence. The aging population poses a severe medical concern due to the burden it places on healthcare systems and the general public as well as the prevalence of diseases and impairments associated with old age. In this chapter, we discuss organ failure during ageing as well as ageing of the hypothalamic-pituitary-adrenal axis and drugs that can regulate it. A much-debated subject is about ageing and regeneration. With age, there is a gradual decline in the regenerative properties of most tissues. The goal of regenerative medicine is to restore cells, tissues, and structures that are lost or damaged after disease, injury, or ageing. The question arises as to whether this is due to the intrinsic ageing of stem cells or, rather, to the impairment of stem-cell function in the aged tissue environment. The risk of having a stroke event doubles each decade after the age of 55. Therefore, it is of great interest to develop neurorestorative therapies for stroke which occurs mostly in elderly people. Initial enthusiasm for stimulating restorative processes in the ischaemic brain with cell-based therapies has meanwhile converted into a more balanced view, recognising impediments related to survival, migration, differentiation, and integration of therapeutic cells in the hostile aged brain environment. Therefore, a current lack of understanding of the fate of transplanted cells means that the safety of cell therapy in stroke patients is still unproven. Another issue associated with ischaemic stroke is that patients at risk for these sequels of stroke are not duly diagnosed and treated due to the lack of reliable biomarkers. However, recently neurovascular unit-derived exosomes in response to Stroke and released into serum are new plasma genetic and proteomic biomarkers associated with ischaemic stroke. The second valid option, which is also more economical, is to invest in prevention.
MeSH term(s)	Aged ; Humans ; Stroke/therapy ; Brain Ischemia/therapy ; Hypothalamo-Hypophyseal System ; Proteomics ; Pituitary-Adrenal System ; Aging/physiology ; Ischemic Stroke
Language	English
Publishing date	2023-04-29
Publishing country	United States
Document type	Journal Article
ISSN	0306-0225 ; 0096-8757
ISSN	0306-0225 ; 0096-8757
DOI	10.1007/978-3-031-26576-1_16
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