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Improved rat stroke model by intraluminal middle cerebral artery occlusion: a special emphasis on surgical technique

100%

Oradan A., Hutanu A., Horvath E., Chiriac L., Dobreanu M.

Health Problems of Civilization

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2017

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tom 11

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nr 3

Various rodent models have been developed for examining either focal or global cerebral ischemia so far, but the most used model is the rat middle cerebral artery occlusion by intraluminal filaments, followed by reperfusion, and 2,3,5-triphenyltetrazoliumchloride or Cresyl Violet/Nissl staining for evaluation of the region of interest. Like other surgical procedures, this one is prone to various complications (excessive bleeding, vascular or nerve lesions) and failure related to the surgical technique. We focused on detailed surgical techniques, along with data from literature, in order to reduce the complications and increase the chance of experiment success. Magnetic Resonance Imaging evaluation with 3D reconstruction of the ischemic area opens new perspectives on investigations into the ischemic brain, having the advantage of being noninvasive as an alternative to gold histological standard for measuring the infarct size, being the only one accesible in surviving subjects.

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FGF2-FGFR2 binding domain complex as a model system for studies of electromagnetic field effects on brain cells

86%

Estkowska J., Peplowski L., Nowak W.

Current Topics in Biophysics. Supplement

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2011

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tom 34

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nr A: Posters

3

Photochemically-induced vascular damage in brain cortex. Transmission and scanning electron microscopy study

86%

Gajkowska B., Frontczak-Baniewicz M., Gadamski R., Barskov I.

Acta Neurobiologiae Experimentalis

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1997

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tom 57

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nr 3

4

Influence of the corticotropin releasing hormone (CRH) on the brain-blood barrier permeability in cerebral ischemia in rats

86%

Hendryk S., Jedrzejowska-Szypulka H., Josko J., Jarzab B., Dohler K. D.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 1

The increase in the blood-brain barrier (BBB)permeability and a developing cerebral oedema due to the ischemic infarction appear a few hours,and intensify during a few days,after closing the carotid arteries.It fails to be clear,however,what causes the increase in the microvessels damage,and whether the damage is a secondary result of the vasoactive substances released by the neurones and glia cells damaged by the ischemia.CRH,which plays an essential role in integrative the nervous,endocrine, and immunological systems,has a positive effect on the decrease in the permeability of the BBB damaged by various physical and chemical factors.Therefore,the examination of the CRH role in the cerebral ischemia may prove useful for explaining the processes taking place in the foci of the cerebral infarction and their environment. The experiment was carried out on rats which,20 minutes before closing of both internal carotid arteries,was administered 10 µg CRH to cerebrospinal fluid via cisterna magna of the brain.The BBB permeability was measured 30 minutes,3 hours,3 days,and 7 days after closing the arteries.The experiment has shown the CRH protective effect on the BBB and its consequent effect on the decrease in the BBB permeability which appears in the 3 hours after closing the arteries (p<0.05),and is high significant during the chronic phase of the cerebral ischemia (p<0.03).It can be thus concluded that CRH,by affecting directly the endothelium of the cerebral vessels, decreases the endothelial damage in the acute phase of the ischemia.The decrease is noted to be more significant in the chronic phase of the ischemia;such an effect can be attributed to CRH stimulating the hypothalamic-adrenal axis,and to the secondary activation of the mechanisms decreasing the BBB permeability.

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Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia

72%

Krysl D., Deykun K., Lambert L., Pokorny J., Mares J.

Journal of Physiology and Pharmacology

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2012

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tom 63

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nr 2

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Hyperoxia intensifies postischemic lipid peroxidation in gerbil brain synaptosomes

72%

Gordon-Majszak W. L., Lazarewicz J. W.

Bulletin of the Polish Academy of Sciences. Biological Sciences

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1990

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tom 38

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nr 1-12

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Experimental approaches to enhance functional recovery following cerebral ischemia

72%

Jolkkonen J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Stroke is a major cause of adult disability that poses an enormous healthcare burden. Effective pharmacotherapy for stroke remains an unmet need. Development of restorative therapies has been identified as a potential alternative in stroke. Emerging understanding of brain repair and plasticity mechanisms have revealed therapeutic targets including inhibition of axonal sprouting (e.g., Nogo, MAG), altered perilesional GABA and glutamate receptor signaling, endogenous neurogenesis and angiogenesis. The main advantage with restorative therapies is the delayed treatment after acute necrotic cell death, when patients are stable. In addition, restorative therapies can be combined with intensive rehabilitation and medication for poststroke complications to further facilitate recovery process. The problem with patient studies is, however, that many pharmaceutical companies have scaled down their stroke programs, because of failures with neuroprotective compounds. We should convince industry that restorative drugs target completely different mechanisms with extended therapeutic time window offering an attractive approach to help stroke patients.

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Activation of NMDA-sensitive glutamate receptors triggers release of taurine in rabbit hippocampus during ischemia

72%

Puka M., Salinska E., Pluta R., Lazarewicz J. W.

Bulletin of the Polish Academy of Sciences. Biological Sciences

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1990

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tom 38

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nr 1-12

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Protein kinase C - like immunoreactivity in gerbil hippocampus after a transient cerebral ischemia

72%

Gajkowska B., Domanska-Janik K., Viron A.

Folia Histochemica et Cytobiologica

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1994

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tom 32

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nr 2

10

Ultrastructural evaluation of phagocytic function of perivascular cells and interstitial microglia in the brain of rats surviving one year after cardiac arrest-induced global cerebral ischemia

72%

Walski M., Frontczak-Baniewicz M., Wojewodzka U., Gajkowska B.

Acta Biologica Cracoviensia. Series Zoologia

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2003

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tom 45

11

Glutamate excitotoxicity in transient global cerebral ischemia

72%

Paschen W.

Acta Neurobiologiae Experimentalis

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1996

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tom 56

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nr 1

12

Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex

72%

Kundrotiene J., Wagner A., Liljequist S.

Acta Neurobiologiae Experimentalis

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2004

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tom 64

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nr 2

13

mRNA transfection – a novel, clinically applicable tool for the robust induction of transient transgene expression in human mesenchymal stem cells

58%

Nowakowski A., Andrzejewska A., Kozlowska H., Walczak P., Lukomska B., Janowski M.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Adult bone marrow-derived mesenchymal stem cells (hMSCs) display a spectrum of functional properties. Transplantation of these cells improves the clinical outcome in experimental models of cerebral ischemia and spinal cord injury. Therapeutic effects have been reported in stroke after the systemic delivery of MSCs. A minimally invasive, intraarterial route is an attractive method for stem cell transplantation to the injured brain. However, MSCs lack the intrinsic mechanisms that enable homing of the cells to the area of infarction. Recent studies suggest that genetic manipulation can promote the forced expression of certain molecules responsible for adhesion and transendothelial migration of systemically delivered cells. It is anticipated that, for cell homing to the brain after intra-arterial delivery, the transient expression of integrins should be sufficient for diapedesis to occur. Since the capacity of MSCs to undergo functional transfection using pDNA is very low, we investigated an mRNA transfection method for the expression of transgenes in MSCs in order to overcome the limitations of the pDNA approach. Methods: Human mesenchymal stem cells (hMSC, PT-2501, Lonza) were thawed and cultured in medium MSCBM (PT-3238, Lonza) supplemented with 10% MCGS (PT-4106E, Lonza), L-glutamine (PT4107E, Lonza), and gentamicin sulfate (GA-1000, PT-4504E, Lonza). Cells were maintained in a humidified atmosphere at 37°C and 5% CO2 using 75 cm2 flasks. For transfection experiments, hMSCs were transferred to 24-well plates and seeded at a density of 15 000 cells/well. For transgene induction experiments, pDNA-eGFP (BD Biosciences) at a dose of 0.5 and 1.0 µg/well, and mRNA-eGFP (StemGent) at doses of 0.12, 0.25, and 0.5 µg/well were used. The Lipofectamine® 2000 (Invitrogen), TransIT-2020 (Mirus), and StemfectTM RNA Transfection Kit (StemGent) were used as transfection agents. After transfection, cells were maintained in culture conditions up to 21 days. Transfection efficiency was assessed by confocal microscopy using GFP fluorescent signal detection. Results: MSC pDNA-eGFP transfection results in a dramatically low efficiency, less than 1% of the cell population in each of the tested conditions. In contrast, mRNA-eGFP transfection resulted in an efficiency exceeding 95% in each of the tested conditions. This difference was highly statistically significant (P<0.001). Furthermore, cellular GFP level, and the persistence of transfection was dependent on the mRNA dose and the type of transfection agent. It was found that the dose of mRNA-eGFP 0.5 µg/well and the use of Lipofectamine was the most effective method with transgene expression up to three weeks. Conclusions: The mRNA transfection is a robust, clinically applicable tool for inducing the transient expression of transgenes in hMSCs, which are otherwise difficult to transfect by vectors that do not incorporate into the host genome. Using this method, application of engineered MSC could revolutionize regenerative medicine. Supported by a National Centre for Research and Development grant No 101 in ERA-NET NEURON project: “MEMS-IRBI”

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In search for effective modulators of the proteasome activity

58%

Karpowicz P., Stoj J., Gaczynska M., Osmulski P., Jankowska E.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Proteasome is a multi-activity enzyme involved in a ubiquitin-dependent turnover of cytoplasmic and nuclear proteins. It recognizes and digests short-lived regulatory proteins, influencing cellular processes as crucial as progression of the cell cycle, transcription, oncogenesis and flux of substrates through metabolic pathways. The enzyme is responsible also for the housekeeping chores, degrading misfolded or oxidatively damaged proteins. Defects in the proteasome action play a causal role in development of a number of diseases, among which are cerebral ischemia and neurodegenerative disorders such as Huntington’s, Alzheimer’s, and Parkinson’s diseases. Being a multifunctional proteolytic machinery, the proteasome must act under a strict control to prevent massive degradation of all intracellular proteins, which would result in a cell death. One of the levels of such a control is the proteasome structure itself. The core particle called 20S proteasome is a barrel-like structure made up of four rings of seven subunits each. The outer (α) rings play predominantly a structural role forming a kind of a gated channel leading to the proteolytic chamber. The inner-β-rings harbor six active sites, concealed inside the cavity formed by the β subunits. So far, the only proteasome-targeting agents used in clinics are competitive inhibitors, directly blocking the enzyme’s active sites. However, the multi-subunit barrel-like structure of the 20S proteasome encourages to test compounds which can target allosteric interactions between subunits and influence the gating mechanism, involved in the control of the substrates’ uptake. Such modulators may provide a precise and substrate-specific regulation of the proteasome catalytic performance. Additionally, targeting the allosteric interactions may enable not only inhibition but also stimulation of the proteasome, which is crucial in managing disorders connected with the proteasome not sufficient activity, such as neurodegenerative diseases. A variety of protein ligands, interacting with the outer ring of the 20S proteasome and modulating its activity, is already known. They can serve as templates for design of putative small-molecule allosteric drugs. In an effort to find synthetic compounds able to enhance or suppress the performance of the proteasome active centers we utilize one of such protein ligands – HIV-1 Tat protein. The protein is known to inhibit the core proteasome and to interfere with the physiological PA28 activator in its binding to the 20S. G48RKKRRQRRRPS59 fragment of HIV-1 Tat (Tat1) occurred to be very efficient in the 20S proteasome inhibition. By single and multiple alanine substitutions we have recognized “hot spots” in the sequence of Tat1. NMR and molecular dynamics calculations allowed us to correlate these putative pharmacophores with the structural turns. By introduction of a non-peptide turn-inducing modification to the Tat1 sequence we have obtained the derivatives highly toxic for human cultured cancer cells HeLa.S3. The work was supported by grants: NCN 2011/01/B/ST5/06616 and DS/8440-4-0172-2

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Corticotropin releasing hormone [CRH] increases beta-endorphin [beta-end like] concentration in cerebrospinal fluid of rats with vasospasm following subarachnoid hemorrhage

58%

Henryk S., Josko J., Jedrzejowska-Szypulka H., Jarzab B., Dohler K. D.

Journal of Physiology and Pharmacology

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1999

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tom 50

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nr 3

Ograniczanie wyników

Improved rat stroke model by intraluminal middle cerebral artery occlusion: a special emphasis on surgical technique

FGF2-FGFR2 binding domain complex as a model system for studies of electromagnetic field effects on brain cells

Photochemically-induced vascular damage in brain cortex. Transmission and scanning electron microscopy study

Influence of the corticotropin releasing hormone (CRH) on the brain-blood barrier permeability in cerebral ischemia in rats

Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia

Hyperoxia intensifies postischemic lipid peroxidation in gerbil brain synaptosomes

Experimental approaches to enhance functional recovery following cerebral ischemia

Activation of NMDA-sensitive glutamate receptors triggers release of taurine in rabbit hippocampus during ischemia

Protein kinase C - like immunoreactivity in gerbil hippocampus after a transient cerebral ischemia

Ultrastructural evaluation of phagocytic function of perivascular cells and interstitial microglia in the brain of rats surviving one year after cardiac arrest-induced global cerebral ischemia

Glutamate excitotoxicity in transient global cerebral ischemia

Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex

mRNA transfection – a novel, clinically applicable tool for the robust induction of transient transgene expression in human mesenchymal stem cells

In search for effective modulators of the proteasome activity

Corticotropin releasing hormone [CRH] increases beta-endorphin [beta-end like] concentration in cerebrospinal fluid of rats with vasospasm following subarachnoid hemorrhage