Single Versus Repetitive Traumatic Brain Injury: Current Knowledge on the Chronic Outcomes, Neuropathology and the Role of TDP-43 Proteinopathy

Janković Tamara,Pilipović Kristina 한국뇌신경과학회 2023 Experimental Neurobiology Vol.32 No.4

Traumatic brain injury (TBI) is one of the most important causes of death and disability in adults and thus an important public health problem. Following TBI, secondary pathophysiological processes develop over time and condition the development of different neurodegenerative entities. Previous studies suggest that neurobehavioral changes occurring after a single TBI are the basis for the development of Alzheimer's disease, while repetitive TBI is considered to be a contributing factor for chronic traumatic encephalopathy development. However, pathophysiological processes that determine the evolvement of a particular chronic entity are still unclear. Human post-mortem studies have found combinations of amyloid, tau, Lewi bodies, and TAR DNA-binding protein 43 (TDP-43) pathologies after both single and repetitive TBI. This review focuses on the pathological changes of TDP-43 after single and repetitive brain traumas. Numerous studies have shown that TDP-43 proteinopathy noticeably occurs after repetitive head trauma. A relatively small number of available preclinical research on single brain injury are not in complete agreement with the results from the human samples, which makes it difficult to draw specific conclusions. Also, as TBI is considered a heterogeneous type of injury, different experimental trauma models and injury intensities may cause differences in the cascade of secondary injury, which should be considered in future studies. Experimental and post-mortem studies of TDP-43 pathobiology should be carried out, preferably in the same laboratories, to determine its involvement in the development of neurodegenerative conditions after one and repetitive TBI, especially in the context of the development of new therapeutic options.

Graphene-based antibacterial composite coatings electrodeposited on titanium for biomedical applications

Janković,, Ana,Eraković,, Sanja,Vukaš,inović,-Sekulić,, Maja,Miš,ković,-Stanković,, Vesna,Park, Soo Jin,Rhee, Kyong Yop Elsevier 2015 Progress in organic coatings Vol.83 No.-

<P><B>Abstract</B></P> <P>The graphene based silver/hydroxyapatite/graphene (Ag/HAP/Gr) composite coatings were produced by electrophoretic deposition (EPD) on titanium to assemble porous bioactive homogenous coatings, with improved corrosion stability in simulated body fluid (SBF). Novel composite coatings were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), Raman spectroscopy, X-ray photoelectron analysis (XPS) and electrochemical impedance spectroscopy (EIS). The improved properties of graphene based coatings in respect to the graphene-free coatings, as a consequence of toughening action of graphene, were demonstrated: reduced surface cracks, better mechanical resistance (hardness and elastic modulus increased by 10%) and enhanced thermal stability, while the Ca/P ratio was closer to the stoichiometric value. The bioactivity of Ag/HAP/Gr composite coatings was proved by a newly formed apatite layer in SBF with enhanced corrosion stability, while antibacterial activity against <I>Staphylococcus aureus</I> and <I>Escherichia coli</I> and noncytotoxicity against healthy peripheral blood mononuclear cells (PBMC) indicate the high potential for biomedical applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Novel graphene based composite coating on titanium obtained by electrophoretic deposition. </LI> <LI> Homogenous, non-toxic Ag/HAP/Gr coating with improved mechanical properties. </LI> <LI> New apatite layer formation in SBF has proved the coating bioactivity. </LI> <LI> Diminished bacterial growth of <I>S. aureus</I> and <I>E. coli</I> after only 3h of exposure. </LI> </UL> </P>

Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant

Eldina Rizvić,Goran Janković,Miroslav M. Savić 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.4

Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline (10–6 M and especially 10–7 M) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations (10–4 M and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor Nw-nitro-L-arginine methyl ester (L-NAME; 10–4 M) or NO scavanger OHB12 (10–3 M), as well as non-specific inhibition of K+-channels with tetraethylammonium (TEA; 10–3 M), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10–5 M) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at 3×10–7 and 10–6 M, but not at the highest concentration (10–4 M). Neither the 5-HT1D-receptor selective antagonist BRL 15572 (10–6 M) nor 5-HT7 receptor selective antagonist SB 269970 (10–6 M) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and K+-channels and activation of some methiothepinsensitive receptors, possibly of the 5-HT2B subtype.

Electrochemical synthesis of nanosized hydroxyapatite/graphene composite powder

Vesna Mišković-Stanković,Sanja Eraković,Ana Janković,Maja Vukašinović-Sekulić,Miodrag Mitrić,Young Chan Jung,Soo Jin Park,Kyong Yop Rhee 한국탄소학회 2015 Carbon Letters Vol.16 No.4

Electrochemical synthesis was employed to prepare a novel hydroxyapatite/graphene (HAP/ Gr) composite powder suitable for medical applications as a hard tissue implant (scaffold). The synthesis was performed in a homogeneous dispersion containing Na2H2EDTA·2H2O, NaH2PO4 and CaCl2 with a Ca/EDTA/PO4 3− concentration ratio of 0.25/0.25/0.15M, along with 0.01 wt% added graphene nanosheets, at a current density of 137 mA cm−2 and pH value of 9.0. The field emission scanning electron microscopy and transmission electron microscopy observations of the composite HAP/Gr powder indicated that nanosized hydroxyapatite particles were uniformly placed in the graphene overlay. Raman spectroscopy, Fourier transform infrared spectroscopy and X-ray diffraction confirmed graphene incorporation in the HAP/Gr powder. The electrochemically prepared HAP/Gr composite powder exhibited slight antibacterial effect against the growth of the bacterial strain Staphylococcus aureus.

Processing and Characterisation of Hybrid Aramid Fabrics Reinforced with Cross-linked Electrospun PVB Composite Nanofibres

Vera Obradović,Dušica B. Stojanović,Ivona Janković Častvan,Vesna Radojević,Petar S. Uskoković 한국섬유공학회 2018 Fibers and polymers Vol.19 No.9

The aim of this study was to fabricate a new kind of hybrid fabric composites with the cross-linked electrospun poly(vinyl butyral) (PVB) composite nanofibres. The experiments were performed with the 10 wt.% PVB/ethanol solution for electrospinning where the modified silica nanoparticles (mSiO2), the oxidised single-walled carbon nanotubes (o- SWCNT) and the o-SWCNT/mSiO2 hybrid nanoparticles were added to the solution. The electrospun fibres were crosslinked with glutaraldehyde (GA) afterwards in order to reinforce the composite structure by bonding to the p-aramid fabrics. The chemical and thermo-mechanical properties of the hybrid fabric composites were evaluated. The greatest improvement in thermo-mechanical properties was achieved by the sample which contained the cross-linked PVB fibres with the o- SWCNT/mSiO2 hybrid nanoparticles.

Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant

Eldina Rizvić,Goran Janković,Miroslav M. Savić 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.13 No.1

Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline (10^–6 M and especially 10^–7 M) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations (10^–4 M and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor N^w-nitro-L-arginine methyl ester (L-NAME; 10^–4 M) or NO scavanger OHB₁₂ (10^–3 M), as well as non-specific inhibition of K⁺-channels with tetraethylammonium (TEA; 10^–3 M), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10^–5 M) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at 3×10^–7 and 10^–6 M, but not at the highest concentration (10^–4 M). Neither the 5-HT₁_D-receptor selective antagonist BRL 15572 (10^–6 M) nor 5-HT₇ receptor selective antagonist SB 269970 (10^–6 M) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and K⁺-channels and activation of some methiothepin sensitive receptors, possibly of the 5-HT_2B subtype.

Silver/poly(vinyl alcohol)/chitosan/graphene hydrogels – Synthesis, biological and physicochemical properties and silver release kinetics

Neš,ović,, Katarina,Janković,, Ana,Kojić,, Vesna,Vukaš,inović,-Sekulić,, Maja,Perić,-Grujić,, Aleksandra,Rhee, Kyong Yop,Miš,ković,-Stankovi Elsevier 2018 Composites. Part B, Engineering Vol.154 No.-

<P><B>Abstract</B></P> <P>This study presents the synthesis of novel silver/poly(vinyl alcohol)/chitosan/graphene (Ag/PVA/CHI/Gr) nanocomposite hydrogels by <I>in situ</I> electrochemical reduction of silver ions in the hydrogel matrix and their thorough characterization by UV–visible and Raman spectroscopies, field-emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and silver release measurements. The influence of chitosan content on the incorporation and stabilization of silver nanoparticles (AgNPs) was investigated, and we found that hydrogels with higher chitosan content contain higher amounts of AgNPs. In addition, the cytotoxicity and antibacterial activity of Ag/PVA/CHI/Gr nanocomposite hydrogels were evaluated. Based on <I>in vitro</I> investigations, the obtained materials exhibit diffusion-controlled release profiles over 28 days, strong antibacterial activity against <I>Staphylococcus aureus</I> and <I>Escherichia coli</I> bacterial strains, and no cytotoxicity toward human and mice fibroblast cell lines.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>In situ</I> electrochemical synthesis of silver nanoparticles in PVA/CHI/Gr hydrogels. </LI> <LI> Effect of chitosan concentration on the amount of embedded silver nanoparticles. </LI> <LI> Effect of chitosan concentration on the silver release kinetics. </LI> <LI> Strong antibacterial activity against <I>S. aureus</I> and <I>E. coli</I>. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

In vitro investigation of electrophoretically deposited bioactive hydroxyapatite/chitosan coatings reinforced by graphene

Đ,oš,ić,, Marija,Eraković,, Sanja,Janković,, Ana,Vukaš,inović,-Sekulić,, Maja,Matić,, Ivana Z.,Stojanović,, Jovica,Rhee, Kyong Yop,Miš,ković Elsevier 2017 Journal of industrial and engineering chemistry Vol.47 No.-

<P><B>Abstract</B></P> <P>Graphene (Gr) and natural polymer chitosan (CS) were introduced to hydroxyapatite (HAP) to produce a three-component composite coating, which was fabricated by cathodic electrophoretic deposition on Ti substrates in an ethanol suspension. These HAP/CS/Gr coatings were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and electrochemical measurements and found that the graphene into HAP/CS composites significantly improves their morphology, thermal stability, and bioactivity. Both HAP/CS and HAP/CS/Gr composite coatings are classified as non-cytotoxic when tested against healthy peripheral blood mononuclear cells (PBMC), while antibacterial activity against <I>Staphylococcus aureus</I> and <I>Escherichia coli</I> could not be verified.</P>