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Tytuł:
Oxygen-glucose deprivation in organotypic hippocampal cultures leads to cytoskeleton rearrangement and immune activation : link to the potential pathomechanism of ischaemic stroke
Autorzy:
Trojan, Ewa
Lekka, Małgorzata
Wesołowska, Julita
Basta-Kaim, Agnieszka
Bryniarska-Kubiak, Natalia
Kubiak, Andrzej
Opis:
Ischaemic stroke is characterized by a sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. As a result of this process, neurons in the ischaemic core are deprived of oxygen and trophic substances and are consequently destroyed. Tissue damage in brain ischaemia results from a complex pathophysiological cascade comprising various distinct pathological events. Ischaemia leads to brain damage by stimulating many processes, such as excitotoxicity, oxidative stress, inflammation, acidotoxicity, and apoptosis. Nevertheless, less attention has been given to biophysical factors, including the organization of the cytoskeleton and the mechanical properties of cells. Therefore, in the present study, we sought to evaluate whether the oxygen-glucose deprivation (OGD) procedure, which is a commonly accepted experimental model of ischaemia, could affect cytoskeleton organization and the paracrine immune response. The abovementioned aspects were examined ex vivo in organotypic hippocampal cultures (OHCs) subjected to the OGD procedure. We measured cell death/viability, nitric oxide (NO) release, and hypoxia-inducible factor $1\alpha$ (HIF-$1\alpha$) levels. Next, the impact of the OGD procedure on cytoskeletal organization was evaluated using combined confocal fluorescence microscopy (CFM) and atomic force microscopy (AFM). Concurrently, to find whether there is a correlation between biophysical properties and the immune response, we examined the impact of OGD on the levels of crucial ischaemia cytokines (IL-$1\beta$, IL-6, IL-18, TNF-$\alpha$, IL-10, IL-4) and chemokines (CCL3, CCL5, CXCL10) in OHCs and calculated Pearsons’ and Spearman’s rank correlation coefficients. The results of the current study demonstrated that the OGD procedure intensified cell death and nitric oxide release and led to the potentiation of HIF-$1\beta$ release in OHCs. Moreover, we presented significant disturbances in the organization of the cytoskeleton (actin fibers, microtubular network) and cytoskeleton-associated protein 2 (MAP-2), which is a neuronal marker. Simultaneously, our study provided new evidence that the OGD procedure leads to the stiffening of OHCs and a malfunction in immune homeostasis. A negative linear correlation between tissue stiffness and branched IBA1 positive cells after the OGD procedure suggests the pro-inflammatory polarization of microglia. Moreover, the negative correlation of pro- and positive anti-inflammatory factors with actin fibers density indicates an opposing effect of the immune mediators on the rearrangement of cytoskeleton induced by OGD procedure in OHCs. Our study constitutes a basis for further research and provides a rationale for integrating biomechanical and biochemical methods in studying the pathomechanism of stroke-related brain damage. Furthermore, presented data pointed out the interesting direction of proof-of-concept studies, in which follow-up may establish new targets for brain ischemia therapy.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
A simple local navigation system inspired by hippocampal function and its autonomous mobile robot implementation
Autorzy:
Miki, T.
Hayashi, H.
Goto, Y.
Watanabe, M.
Inoue, T.
Tematy:
human-like local navigation
sequence learning
entorhino-hippocampal system
autonomous mobile robot
Pokaż więcej
Wydawca:
Sieć Badawcza Łukasiewicz - Przemysłowy Instytut Automatyki i Pomiarów
Powiązania:
https://bibliotekanauki.pl/articles/384203.pdf  Link otwiera się w nowym oknie
Opis:
We propose a practical simple local navigation system inspired by the sequence learning mechanism of the entorhino-hippocampal system. The proposed system memorizes a route as sequences of landmarks in the same way humans do. The proposed local navigation system includes a local route memory unit, landmark extraction unit, and learning-type matching unit. In the local route memory unit, the concept of the sequence learning mechanism of the entorhino-hippocampal system is implemented using a fully connected network, while a sequence of landmarks is embedded in the connection matrix as the local route memory. This system has two operation modes: learning and recall modes. In learning mode, a sequence of landmarks, i.e. a local route, is represented by enhanced loop connections in the connection matrix. In recall mode, the system traces the stored route comparing current landmarks with the stored landmarks using the landmark extraction and learning-type matching units. The system uses a prospective sequence to match the current landmark sequence with the recalled one. Using a prospective sequence in the route comparison allows confirmation of the correct route and deals with any slight change in the current sequence of landmarks. A certainty index is also introduced for judging the validity of the route selection. We describe a basic update mechanism for the stored landmark sequence in the case of a small change in the local route memory. The validity of the proposed system is confirmed using an autonomous mobile robot with the proposed navigation system.
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Pro-inflammatory cytokines, but not brain- and extracellular matrix-derived proteins, are increased in the plasma following electrically induced kindling of seizures
Autorzy:
Szyndler, Janusz
Osuch, Bartosz
Maciejak, Piotr
Kursa, Miron Bartosz
Chmielewska, Natalia
Wydawca:
Springer Nature
Cytata wydawnicza:
Chmielewska, N., Maciejak, P., Osuch, B. et al. Pro-inflammatory cytokines, but not brain- and extracellular matrix-derived proteins, are increased in the plasma following electrically induced kindling of seizures. Pharmacol. Rep 73, 506–515 (2021). https://doi.org/10.1007/s43440-020-00208-w
Opis:
Background The aim of the study was to evaluate the brain-derived proteins, extracellular matrix-derived protein and cytokines as potential peripheral biomarkers of different susceptibility to seizure development in an animal model of epilepsy evoked by chronic focal electrical stimulation of the brain. Methods The plasma levels of IL-1β (interleukin 1β), IL-6 (interleukin 6), UCH-L1 (ubiquitin C-terminal hydrolase 1), MMP-9 (matrix metalloproteinase 9), and GFAP (glial fibrillary acidic protein) were assessed. The peripheral concentra- tions of the selected proteins were analyzed according to the status of kindling and seizure severity parameters. In our study, increased concentrations of plasma IL-1β and IL-6 were observed in rats subjected to hippocampal kindling compared to sham-operated rats. Results Animals that developed tonic–clonic seizures after the last stimulation had higher plasma concentrations of IL-1β and IL-6 than sham-operated rats and rats that did not develop seizure. Elevated levels of IL-1β and IL-6 were observed in rats that presented more severe seizures after the last five stimulations compared to sham-operated animals. A correlation between plasma IL-1β and IL-6 concentrations was also found. On the other hand, the plasma levels of the brain-derived proteins UCH-L1, MMP-9, and GFAP were unaffected by kindling status and seizure severity parameters. Conclusions The plasma concentrations of IL-1β and IL-6 may have potential utility as peripheral biomarkers of immune system activation in the course of epilepsy and translational potential for future clinical use. Surprisingly, markers of cell and nerve ending damage (GFAP, UCH-L1 and MMP-9) may have limited utility.
Dostawca treści:
Repozytorium Centrum Otwartej Nauki
Artykuł
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