The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage

Background: Although microglia and the Toll-like receptor (TLR) pathway have long been thought to play a role in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), thus far only correlations have been made. In this study, we attempted to solidify the relationship between microglia and the TLR pathway using depletion and genetic knockouts, respectively. Methods: Subarachnoid hemorrhage was induced in TLR4−/−, TRIF−/−, MyD88−/− and wild type C57BL/6 mice by injecting 60 μl of autologous blood near the mesencephalon; animals were euthanized 1 to 15 days after SAH for immunohistochemical analysis to detect microglia or apoptotic cells. Lastly, microglial depletion was performed by intracerebroventricular injection of clodronate liposomes. Results: On post operative day (POD) 7 (early phase SAH), neuronal apoptosis was largely TLR4-MyD88-dependent and microglial-dependent. By POD 15 (late phase SAH), neuronal apoptosis was characterized by TLR4- toll receptor associated activator of interferon (TRIF)-dependence and microglial-independence. Similarly, vasospasm was also characterized by an early and late phase with MyD88 and TRIF dependence, respectively. Lastly, microglia seem to be both necessary and sufficient to cause vasospasm in both the early and late phases of SAH in our model. Conclusion: Our results suggest that SAH pathology could have different phases. These results could explain why therapies tailored to aSAH patients have failed for the most part. Perhaps a novel strategy utilizing immunotherapies that target Toll like receptor signaling and microglia at different points in the patient’s hospital course could improve outcomes

Method for constructing periodic orbits in nonlinear dynamic systems

Method is modification of generalized Newton-Ralphson algorithm for analyzing two-point boundary problems. It constructs sequence of solutions that converge to precise dynamic solution in the sequence limit. Program calculates periodic orbits in either circular or elliptical restricted three-body problems

Computer program offers new method for constructing periodic orbits in nonlinear dynamical systems

Computer program uses an iterative method to construct precisely periodic orbits which dynamically approximate solutions that converge to precise dynamical solutions in the limit of the sequence. The method used is a modification of the generalized Newton-Raphson algorithm used in analyzing two point boundary problems

Rotating charged AdS solutions in quadratic f(T)f(T) gravity

We present a class of asymptotically anti-de Sitter charged rotating black hole solutions in $f(T)$ gravity in $N$-dimensions, where $f(T)=T+\alpha T^{2}$. These solutions are nontrivial extensions of the solutions presented in \cite{Lemos:1994xp} and \cite{Awad:2002cz} in the context of general relativity. They are characterized by cylindrical, toroidal or flat horizons, depending on global identifications. The static charged black hole configurations obtained in \cite{Awad:2017tyz} are recovered as special cases when the rotation parameters vanish. Similar to \cite{Awad:2017tyz} the static black holes solutions have two different electric multipole terms in the potential with related moments. Furthermore, these solutions have milder singularities compared to their general relativity counterparts. Using the conserved charges expressions obtained in \cite{Ulhoa:2013gca} and \cite{Maluf:2008ug} we calculate the total mass/energy and the angular momentum of these solutions.Comment: 11 pages, Version accepted in EPJ

Phase Portraits of general f(T) Cosmology

We use dynamical system methods to explore the general behaviour of $f(T)$ cosmology. In contrast to the standard applications of dynamical analysis, we present a way to transform the equations into a one-dimensional autonomous system, taking advantage of the crucial property that the torsion scalar in flat FRW geometry is just a function of the Hubble function, thus the field equations include only up to first derivatives of it, and therefore in a general $f(T)$ cosmological scenario every quantity is expressed only in terms of the Hubble function. The great advantage is that for one-dimensional systems it is easy to construct the phase space portraits, and thus extract information and explore in detail the features and possible behaviours of $f(T)$ cosmology. We utilize the phase space portraits and we show that $f(T)$ cosmology can describe the universe evolution in agreement with observations, namely starting from a Big Bang singularity, evolving into the subsequent thermal history and the matter domination, entering into a late-time accelerated expansion, and resulting to the de Sitter phase in the far future. Nevertheless, $f(T)$ cosmology can present a rich class of more exotic behaviours, such as the cosmological bounce and turnaround, the phantom-divide crossing, the Big Brake and the Big Crunch, and it may exhibit various singularities, including the non-harmful ones of type II and type IV. We study the phase space of three specific viable $f(T)$ models offering a complete picture. Moreover, we present a new model of $f(T)$ gravity that can lead to a universe in agreement with observations, free of perturbative instabilities, and applying the Om(z) diagnostic test we confirm that it is in agreement with the combination of SNIa, BAO and CMB data at 1$\sigma$ confidence level.Comment: 39 pages, 12 figures, version published in JCA

Structural, spectral studies and catalytic activity of copper (II) complex of valine-containing polymer

A new copper complex of valine-containing polymer was prepared to mimic an active site center in the metalloenzymes. The valine containing polymer VPAV was prepared by modifying the vinyl pyridine-acrylamide copolymer. The polymer VPAV was investigated using IR, 1H-nmr, and thermal analysis then, the structure was proposed based on the theoretical calculation. The copper complex CuII-VPAV was fully characterized by means of different physicochemical methods such as IR, electronic spectroscopy, EPR and thermal analysis. The catalyst CuII-VPAV was used in the oxidation of poly phenol trihydroxybenzene in the presence and absence of H2O2. The catalysis shows a catalytic efficiency of 1.2 × 104 times in terms of first-order rate constant relative to auto-oxidation of the substrates in an aqueous environment in the presence of H2O2 and under mild conditions. Key words; valine; copolymer; oxidation; polyphenol; modifyin

Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease

ImportanceWhile the understanding of inflammation in the pathogenesis of many neurological diseases is now accepted, this special commentary addresses the need to study chronic inflammation in the propagation of cognitive Fog, Asthenia, and Depression Related to Inflammation which we name Brain FADE syndrome. Patients with Brain FADE syndrome fall in the void between neurology and psychiatry because the depression, fatigue, and fog seen in these patients are not idiopathic, but instead due to organic, inflammation involved in neurological disease initiation.ObservationsA review of randomized clinical trials in stroke, multiple sclerosis, Parkinson’s disease, COVID, traumatic brain injury, and Alzheimer’s disease reveal a paucity of studies with any component of Brain FADE syndrome as a primary endpoint. Furthermore, despite the relatively well-accepted notion that inflammation is a critical driving factor in these disease pathologies, none have connected chronic inflammation to depression, fatigue, or fog despite over half of the patients suffering from them.Conclusions and relevanceBrain FADE Syndrome is important and prevalent in the neurological diseases we examined. Classical “psychiatric medications” are insufficient to address Brain FADE Syndrome and a novel approach that utilizes sequential targeting of innate and adaptive immune responses should be studied