bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture as a Complementary Therapy for Alzheimer’s Disease
Authors: Li Haixia , Xiang Qiongyao , Ren Rujing , Wang Gang
Published: December 2024

Alzheimer’s disease (AD) is a significant global medical concern due to the aging population. AD is featured by gradual cognitive impairment, impacting daily functioning and causing behavioral and personality changes, causing disruptive psychiatric symptoms. While pharmacological interventions are the primary clinical approach, their efficacy is variable and limited. Acupuncture, with its distinctive theoretical framework and treatment approach, has garnered attention as a non-pharmacological intervention for AD through extensive preclinical and clinical research. Neurobiological investigations into the machinery of acupuncture in AD have provided compelling evidence of its therapeutic efficacy and unique advantages. This review commences with an in-depth exploration of acupuncture’s clinical applications, emphasizing its various parameters and its potential combination with first-line drugs and other therapies in the context of AD. Subsequently, we delve into the underlying therapeutic mechanisms of acupuncture in AD. Finally, we summarize these aspects, highlight current study limitations, and offer recommendations for future research. Taken together, in a rapidly aging society, both clinical application and mechanistic exploration of acupuncture in AD treatment have gained momentum. This trajectory suggests that acupuncture will continue to make significant strides in AD therapeutics as research progresses.
PET/CT/MRI in Clinical Trials of Alzheimer’s Disease
Authors: Høilund-Carlsen Poul F. , Alavi Abass , Barrio Jorge R.
Published: December 2024

With the advent of PET imaging in 1976, 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET became the preferred method for in vivo investigation of cerebral processes, including regional hypometabolism in Alzheimer’s disease. With the emergence of amyloid-PET tracers, [11C]Pittsburgh Compound-B in 2004 and later [18F]florbetapir, [18F]florbetaben, and [18F]flumetamol, amyloid-PET has replaced FDG-PET in Alzheimer’s disease anti-amyloid clinical trial treatments to ensure “amyloid positivity” as an entry criterion, and to measure treatment-related decline in cerebral amyloid deposits. MRI has been used to rule out other brain diseases and screen for ‘amyloid-related imaging abnormalities’ (ARIAs) of two kinds, ARIA-E and ARIA-H, characterized by edema and micro-hemorrhage, respectively, and, to a lesser extent, to measure changes in cerebral volumes. While early immunotherapy trials of Alzheimer’s disease showed no clinical effects, newer monoclonal antibody trials reported decreases of 27% to 85% in the cerebral amyloid-PET signal, interpreted by the Food and Drug Administration as amyloid removal expected to result in a reduction in clinical decline. However, due to the lack of diagnostic specificity of amyloid-PET tracers, amyloid positivity cannot prevent the inclusion of non-Alzheimer’s patients and even healthy subjects in these clinical trials. Moreover, the “decreasing amyloid accumulation” assessed by amyloid-PET imaging has questionable quantitative value in the presence of treatment-related brain damage (ARIAs). Therefore, future Alzheimer’s clinical trials should disregard amyloid-PET imaging and focus instead on assessment of regional brain function by FDG-PET and MRI monitoring of ARIAs and brain volume loss in all trial patients.
Sensors, vision and networks: From video surveillance to activity
recognition and health monitoring
Authors: Prati Andrea , Shan Caifeng , Wang Kevin I-Kai
Published: December 2024

This paper presents an overview of the state of the art of three
different fields with the shared characteristics of making use of a network
of sensors, with the possible application of computer vision, signal
processing, and machine learning algorithms. Namely, the paper first reports
the state of the art and possible future directions for Intelligent Video
Surveillance (IVS) applications, by recaping the history of the field in
terms of hardware and algorithmic progresses. Then, the existing
technologies of Wireless Sensor Networks (WSNs) are compared and described.
Their applications to human activity recognition (HAR), both from a single
or multiple sensors perspectives, are described and classified, followed by
the current research trends and challenges. Finally, recent advances on
camera-based health monitoring (including vision-based Ambient Assisted
Living and patient monitoring, and camera-based physiological measurements)
are described in full details, with the challenges faced.
A Numerical Study on the Effect of Trim on the Total Resistance of a Container Ship Model in Confined Water
Authors: Martić Ivana , Anušić Barbara , Degiuli Nastia , Grlj Carlo Giorgio
Published: December 2024

Trim optimization is a promising strategy to improve the ship resistance characteristics and consequently increase its energy efficiency. Most of the research conducted so far regarding trim optimization is focused on unrestricted water. Since sailing in restricted water alters the flow and pressure distribution along the ship hull it is necessary to analyse the effect of trim on the total resistance in shallow and confined water. In this study, the effect of trim on the total resistance of the KCS model is analysed using computational fluid dynamics. Numerical simulations of resistance tests are performed for an even keel and four trim angles in restricted water. Numerical uncertainty for the total resistance, sinkage, and trim angle is assessed using different grid resolutions and time steps. The obtained numerical results are validated against the experimental data available in the literature. A detailed analysis of the free surface elevation, wave patterns, distribution of hydrodynamic pressure and wall shear stress, and velocity field on the symmetry plane is carried out. It is shown that a reduction of the total resistance in confined water can be achieved by adjusting the trim angle.
Statistical and Spectral Description of Full-Scale Measurements of Ship Motion in Waves
Authors: Petranović Tamara , Katalinić Marko , Mihanović Hrvoje , Parunov Joško
Published: December 2024

The paper presents new results of the full-scale measurements of waves and ship motions for the research vessel BIOS DVA offshore Split in the Adriatic Sea. Experiments were performed by measuring waves simultaneously and ship responses for five different heading angles and two ship speeds of 7 and 3.5 knots. Waves were recorded by a solar-powered floating buoy, while the ship motion was measured with an Inertial Measurement Unit. Time series of waves and ship motion were analyzed using the STATREL software, and a comparison of statistically and spectrally defined characteristics is presented. The new campaign was organized as the comparison of previous measurements with seakeeping calculations concluded that additional experiments were required to improve the accuracy of seakeeping predictions, especially for the mean zero up-crossing period in the following seas. Therefore, special attention is given to the motion in the following waves in addition to analyzing the influence of ship speed on responses.
Evaluating Roll Damping in Parametric Rolling: Challenges and Approaches
Authors: Turk Anton , Prpić Oršić Jasna , Sulovsky Ivan , Balas Marijana
Published: December 2024

The prediction of parametric rolling in ships remains a critical area of research due to the significant impact on maritime safety and vessel performance. Among the various parameters influencing parametric rolling, roll damping is notoriously challenging to assess due to its nonlinear nature. Accurate prediction of roll damping is essential for reliable parametric rolling simulations. Traditional methods such as the Ikeda method provide valuable insights but are limited in scope, often tailored to specific instances of wave height and wavelength. Decay tests, while useful for individual cases, lack general applicability across a wide range of conditions. Computational Fluid Dynamics (CFD) offers a more comprehensive approach, enabling the analysis of complex interactions between the vessel and the surrounding fluid. However, CFD simulations are computationally intensive and require significant resources. This paper reviews the current methodologies for assessing roll damping, highlighting their advantages and limitations. It underscores the need for integrated approaches that combine empirical data, analytical methods, and advanced simulations to achieve more accurate and reliable predictions of parametric rolling across diverse maritime conditions.
Framework for the Lifetime Extension of Fixed Offshore Platforms in the Northern Adriatic Sea
Authors: Mimica Dalibor , Skejić Davor , Ćatipović Ivan , Parunov Joško
Published: December 2024

Design of fixed offshore platforms is performed in accordance with the regulatory guidance as API Recommended Practice 2A-WSD. However, when extending the lifetime of existing platforms beyond their designed lifetime, structural degradation, marine growth and updated knowledge of the recorded environmental conditions at the exact location where the platform was operated must be taken into account. In the present study, the specific requirements are reviewed for fixed gas exploitation platforms operating in the Croatian part of the north Adriatic Sea. The paper firstly provides overview of the present offshore activities and existing platforms in the Croatian part of the Adriatic. Further, following aspects relevant for the lifetime extension framework of fixed platforms are considered: description of the environmental conditions and seismic characteristics in the north Adriatic Sea, expected severity of the corrosion and marine growth in the region and procedures for strength and fatigue assessment. The aim of the paper is to review state-of-the-art analysis models and computational tools and to serve as the guidance for the engineers involved in the design, inspection, maintenance, and lifetime extension of fixed offshore platforms in the Adriatic. Also, research needs for the improvement of the existing inspection practice are identified.
Usage of ESAB Railtrac FW 1000 and ESAB TFD1 for Mechanized Welding First Phase of Dynalink Project
Authors: Mimica Ratko , Perak Pjero , Ðurđević Neno-Nenad
Published: December 2024

Previous research findings regarding mechanized welding were used as a starting point for project Dynalink. Aim was to test process competitiveness, so mechanized process was compared with hand welding. After successful welding completion with Railtrack, process was retried with Submerged Arc Welding carriage TFD1. Improvements were suggested for further research.
Reconstruction of Ships Outfitting Parts Using Reverse Engineering Methods
Authors: Željković Ivana , Mimica Ratko , Pribudić Tomislav , Bazina Davor , Trebotić Ivan
Published: December 2024

After previous successful reverse engineering projects (ship hull, mast deviation, infrastructure scanning), in this paper reverse engineering methods were used to reconstruct ship piping system. Original drawings of those systems were lost and additionally, designated area suffered damage from fire. Pipes were reconstructed from point clouds and connected with shipyard main database.
Contribution of Wind Assisted Propulsion for a Liner Vessel on a Route in the Adriatic Sea
Authors: Čalić Ante , Katalinić Marko
Published: December 2024

Air pollution from the shipping industry is an ongoing problem that requires exploring innovative technologies for effective resolution. The integration of wind-assisted ship propulsion (WASP) technology offers a promising route towards decarbonisation of the shipping industry. The paper investigates possible fuel savings and CO2 reduction by implementing wind assisted propulsion on a case-study vessel operating on a known route in the Adriatic Sea. The long-term contribution of added wind propulsion is analysed by implementing a Velocity Prediction Program (VPP) and available meteorological data for the area of interest. VPP is modified to predict the contribution of wind propulsion to the overall propulsion necessary to achieve the vessel design speed. The case study quantifies long-term fuel savings for ship operating a liner route and harnessing favourable (predictable) north-west winds, complementing the conventional propulsion systems.
Eye Tracking Technology in Maritime Navigation – Applications and Benefits
Authors: Mišlov Ivan , Barić Mate , Pavić Vinko , Grbić Luka
Published: December 2024

Contemporary maritime industry places a significant emphasis on understanding human cognition and decision-making processes since human error is a predominant factor in over 80% of maritime accidents. With a decreasing number of crew members on ships, seafarers experience increased workloads and responsibilities, leading to a higher likelihood of errors. Eye tracking technology is a method used to monitor and record the movements of a person’s eyes in various situations. By using special glasses or cameras, eye tracking technology records eye movement, gaze duration, blink rate and pupil size, which represent a person’s cognitive and emotional state. This paper analyses the different areas where eye-tracking technology can be applicable in maritime navigation, including research on visual attention, gaze patterns, situational awareness, human-machine interfaces, mental workload and training improvement. The data obtained from various studies on eye tracking technology enable the development of preventive measures and corrections of human errors, especially during the seafarer’s training phase and in equipment layout and design. Eye tracking technology represents a valuable tool to enhance safety and efficiency in maritime navigation, as shown in this paper, which provides a foundation for future research and practical implementation.
Marine Propeller Shaft Dimensions: Proposal to Extend the IACS UR M68 Formula to Alloy Steels
Authors: Roldo Liane , Vulić Nenad
Published: December 2024

On modern ships, particularly small coastal tourist ships around 50 meters in length, ship owners often prefer stainless steel propeller shafts, lubricated by an emulsion of grease and seawater, with no aft sealing. The IACS unified requirement UR M68 prescribes the expression for evaluating shaft diameter based on service loading and tensile strength of the shaft material. However, it should be noted that the formula is only applicable to shafts made of carbon, carbon manganese, and alloyed steels. Stainless steel is excluded. The aim of the paper is to propose the extension of the UR M68 formula for propeller shaft dimensions to cover stainless steel shafts. The chosen dimensions are dependent upon the shaft line concept, especially the type of lubricant, material and predetermined shaft loading (torque or power at the relevant speed). These are currently the only available initial quantities for dimensioning the propeller shaft. Dimensioning propeller shafts, including stainless steel, is a crucial aspect in the development of marine propulsion shafting systems. The presented approach is based upon the fact that the expected failure mechanism of the shaft is fatigue due to cycling loading. Additionally, it highlights and implements the relationship between fatigue strength and the tensile strength of the shaft material.
Emerging Stochastic Methods for Weather-Aware Ship Routing
Authors: Balas Marijana , Prpić-Oršić Jasna , Valčić Marko
Published: December 2024

Optimal ship routing is crucial for enhancing safety, reducing travel time, and minimizing fuel consumption. This paper introduces and examines recent advancements in stochastic optimization techniques, emerging methods and models for weather-aware ship routing. As marine transportation faces increasing challenges due to climate change and extreme weather events, the need for robust and efficient routing strategies has become imperative. A ship route that is subject to uncertainties is considered stochastic. Therefore, a comprehensive overview of emerging stochastic optimization methods that address the inherent uncertainties in weather forecasting and their impact on optimal routing is presented. The paper explores various approaches, including Markov decision processes, stochastic dynamic programming, and scenario-based optimization, highlights their applications in fuel consumption minimization, ensuring safety and improving time reliability. The integration of ensemble weather forecasts and probabilistic models to capture the stochastic nature of oceanic and atmospheric conditions is discussed. Additionally, computational challenges associated with these methods are analyzed along with recent algorithmic improvements that enhance their scalability and real-time applicability. The inclusion of multiple objectives, such as environmental impact and economic factors, within the stochastic framework is also addressed. Finally, a promising research direction is identified and potential synergies with machine learning techniques to further account for an increasingly uncertain marine environment.
SIRE 2.0 – Integration of Human Factors into the Tanker Inspection Program
Authors: Pavić Vinko , Barić Mate , Grbić Luka , Mišlov Ivan
Published: December 2024

The safety of tanker operations has been monitored through the Ship Inspection Report Program (SIRE). This standard kept the operations of tankers as safe as possible through frequent hardware and management process inspections. Lately, the effectiveness of the SIRE inspections in the tanker industry has shown a stagnant trend, and adequate improvement of high safety standards is needed. Accordingly, the SIRE program is being revised to the SIRE 2.0 version with a high focus on human performance and a more human-centric approach. The transition to SIRE 2.0 brings significant changes to the tanker inspection program and is very focused on the crew’s knowledge, skills, and commitment to ensuring the safe conduct of all operations on tanker vessels. The dynamic nature of SIRE 2.0 inspection will require crew and vessel operators to be well-trained, upskilled, and updated continuously. This paper aims to examine key challenges with SIRE 2.0 implementation regarding human elements as each inspection will be different for each vessel.
Assay of Antioxidant Capacity of Human Plasma and CSF in Aging and	Disease
Authors: Alho H. , Leinonen J.S. , Erhola M. , Lönnrot K. , Aejmelaeus R.
Published: December 2024

Oxidative damage to DNA and other macromolecules accumulates with age and has been postulated to be one of the major forms of endogenous damage leading to aging and has been implicated also in initiation of cancer and over a hundred other diseases. The human body has developed an antioxidant (AOX) defense system which contains enzymatic, metal chelating, and free radical scavenging properties. Thus, it is essential to consider the concentration of all AOXs in plasma and CSF when investigating the relationship between diet, oxidative stress, and disease. In the present study a luminometric TRAP-method (total peroxyl radical-trapping potential) was used to determine the activity of all chain breaking AOXs in several clinical states. We have measured TRAP of plasma, cerebrospinal fluid (CSF) and of low density lipoprotein (LDL, TRAPLDL), and the concentrations of main AOX-components (uric acid, protein SH-groups, a-tocopherol, ascorbic acid, ubiquinone and the fraction of unknown antioxidants) to study the effect of: 1) aging, 2) acute infection, 3) diabetes, 4) immobilization and 5) cancer. TRAP of CSF is five times lower than of plasma, mainly due to the low urate concentration in CSF. We have observed that plasma antioxidant defenses respond to the basic metabolic rate and the challenges caused by physiological or pathological stress: i) in a healthy normal population TRAP and TRAPLDL change with age and a substantial proportion of TRAP cannot be attributed to any known AOXs thus indicating the existence of unmeasured an unidentified antioxidant(s); ii) during acute infection and immobilization the exogenous AOXs (vitamin C and E) remained unchanged, whereas the activity of unidentified AOXs of plasma declined sharply; iii) in those NIDDM patients with coronary heart disease plasma TRAP is reduced. In conclusion, TRAP has revealed important information for evaluating the AOX status of human plasma, CSF and LDL. According to our studies, important, possibly endogenous AOXs still remain to be identified.
Mitochondrial Activity in the Mapping of Functional Brain Changes	in Schizophrenia
Authors: Prince Jonathan A. , Oreland Lars
Published: December 2024

The main contributors to the search for functional brain changes in schizophrenia in the past years have employed imaging techniques such as positron emission tomography (PET), single photon emmission computed tomography (SPECT), and magnetic resonance imaging (MRI). Our laboratory has applied a novel strategy involving the post-mortem measurement of the mitochondrial respiratory chain enzyme cytochrome-c-oxidase (COX) to address the question of regional metabolic changes in schizophrenia. This approach is based upon a strong body of evidence which indicates that neuronal COX is highly regulated by the energy demands of the cell and as such represents an endogenous marker of cellular energy metabolism over time. Our original findings indicated that COX activity may be reduced in the striatum and frontal cortex consistent with the concept that a state reduced activity in cortico-striatal circuits may underlie schizophrenia. Subsequent studies from our laboratory on the effects of neuroleptics, PCP, and methamphetamine on animals, have provided additional evidence that a state of dopaminergic overactivity or glutamatergic underactivity produces a hypometabolic state similar to that which is evident in the brains of schizophrenics.
Relationship between Behavioral Recovery from Unilateral 6-OHDA	Lesion of the Substania Nigra and Changes in the Tuberomammillary-Striatal	Projection as Measured by HRP-Labelling
Authors: Morgan S. , Baker D. , Huston J.P.
Published: December 2024

The tuberomammillary nucleus (TM) is the only known neuronal cell group in the brain which contains histamine. There is evidence for a reciprocal relationship between the effects of histamine and dopamine on behavior. A unilateral lesion of dopamine cells in the Substantia Nigra (SN) results in asymmetrical behavior, and recovery from this asymmetry was previously found to be associated with asymmetrical changes in the nigro-striatal projection as determined by anatomical tracing technique. In view of the apparent opposing interaction between the TM and the SN, we examined whether the tuberomammillary-striatal projection also shows changes after a unilateral lesion of the SN. Rats had 6-OHDA injected into one substantia nigra and were tested for behavioral asymmetry over a 15 day period. Horseradish peroxidase (HRP) was then deposited in the caudate-putamen (CPU) ipsilateral to the lesion. Controls devoid of a lesion had the tracer deposited in either the right of left CPU. More HRP-labeled cells were found in the anterior part of TM ipsilateral to the lesion in the animals which failed to recover from lesion-induced asymmetry in turning behavior, as compared to normal controls or animals which showed behavioral recovery. The labeled cells in the anterior part of the ipsilateral TM were smaller in animals examined 15 days after the lesions than in the control animals. The results indicate an increase in HRP uptake or transport in the anterior part of the tuberomammillary-striatal projection predominantly ipsilateral to the lesion in animals which failed to recover from lesion induced asymmetry. Previously, we had found an opposite effect in the nigro-striatal projection, namely an increase in HRP uptake or transport only in animals which recovered from their lesion induced asymmetry. The results are discussed in terms of the evidence for a reciprocal relationship between the TM- and SN-striatal systems.
Excitatory Amino Acids in Epilepsy
Authors: Urbanska Ewa M. , Czuczwar Stanislaw J. , Kleinrok Zdzislaw , Turski Waldemar A.
Published: December 2024

Epilepsy has been described as a neurological disorder with a prevalence rate estimated at approximately 0.5% of population. In recent years there have been significant advances in our understanding of the contribution of excitatory glutamatergic transmission to seizures. Glutamate appeared to participate in the initiation, propagation and maintenance of epileptic activity. In epileptic patients, changes in glutamate concentration and receptor function were found. Intracerebral or systemic administration of glutamate receptor agonists has become a popular way to induce seizures in rodents. Glutamate antagonists were shown to be potent anticonvulsants in varying experimental seizure models determined genetically, induced chemically and electrically, or due to kindling. A potential therapeutic role for drugs affecting glutamatergic mechanisms in epilepsy has not yet been defined but is constantly attracting interest. In this review we summarize data from studies performed in humans and animals and focus on iono- and metabotropic excitatory amino acid receptor-mediated events in seizures and epilepsy.
Polymeric hydrogels placed into a fimbria-fornix lesion cavity	promote fiber (re)growth: a morphological study in the rat
Authors: Duconseille Elee , Woerly Stéphane , Kelche Christian , Will Bruno , Cassel Jean-Christophe
Published: December 2024

To examine the regeneration capacity of dorsal septohippocampal neurons in the presence of an artificial growth-promoting substrate, biocompatible polymeric hydrogels were implanted between the septum and the hippocampus in a fimbria-fornix lesion cavity. Unmodified (control) or aminosugar-containing (glucosamines or N-acetyl-glucosamines) hydrogels were implanted immediately or ten days after the lesions. Six months later, brain sections were processed for cresyl-violet, acetylcholinesterase, and immunocytochemical (glial fibrillary acidic protein, protein S100, neurofilaments, laminin, fibronectin) staining. All hydrogels were well integrated in the brain, constituting a stable bridge between the septum and the hippocampus. Weak gliosis occasionally surrounded the hydrogel in rats from the immediate-implantation group, whereas a more pronounced gliosis was observed in those from the delayed-implantation group. The hydrogels contained blood vessels and were invaded by host cells including astrocytes. Astrocytes formed a loose tissue network filling the porous structure of the hydrogels. Within the hydrogels, laminin-, fibronectin- or neurofilaments-immunopositive networks were also observed. Moreover, numerous acetylcholinesterase-positive fibers penetrated into the hydrogels from the septal, cortical and striatal areas. Fibre penetration was most important in the N-acetylglucosamines-containing hydrogels. Despite these features, the hippocampus failed to show any increase of acetylcholinesterase-staining as compared to that seen in lesion-only rats. These results confirm the regeneration capacity of severed septohippocampal neurons into polymeric substrates used as a bridge inserted in a fimbria-fornix lesion cavity. As such, biomaterials might be of clinical interest not only in the case of spinal cord sections, but also in cases of brain trauma.
The effect of neurotrophic pyrimidine heterocyclic compounds,	MS-818 and MS-430, on the regeneration of injured peripheral nerves
Authors: Itoh Soichiro , Samejima Hirotake , Shinomiya Kenichi , Awaya Akira
Published: December 2024

The effects of pyrimidine heterocyclic compounds (MS-818 and MS-430) on nerve regeneration were evaluated using the cut-and-suture model of the right sciatic nerve of Wistar rats. After surgery, 1 or 5 mg/kg/day of MS-818 or MS-430 was intraperitoneally administered for 21 days. Control rats received the same surgery, but were administered saline instead of a drug. Each week from week 2, evoked muscle action potentials were recorded on the calf muscle to compare the ratio of latency and amplitude between tbe experimental and non-treated side. The specimens were taken from the tibial nerve for light microscopic observation; and the diameter, density and % axon area of myelinated axons were evaluated. Tbe results of EMG and histology suggest that administration of MS-818 is more effective than that of MS-430 and that administration of 5 mg/kg/day has a higher promoting effect than that of 1 mg/kg/day for sprouting and elongation of the severed nerve. These new neurotrophic pyrimidine compounds may be a group of possible substances effective in facilitating nerve regeneration.
Detection and follow-up of homonymous visual field defects	perimetric essentials for evaluation of spontaneous recovery
Authors: Schiefer U. , Skalej M. , Dietrich T.J. , Braun C.
Published: December 2024

Clinical detection and follow-up of homonymous visual field defects require appropriate perimetric procedures: since postgeniculate lesions are usually characterised by absolute scotomata, time consuming threshold methods can be replaced by supraliminal strategies with comparatively high stimulus densities. Compared with equidistant rectangular grids, a centripetal stimulus condensation represents the physi-ological conditions more adequately and thus is more effective. It allows one to differentiate central changes of the visual field, like macular sparing or splitting, which also interfere with reading performance. This procedure requires test points to be located to either side of the verti-cal meridian, rather than directly on it. Multimodal assessment of visual subfunctions (using static, kinetic or colour test points, random dot patterns or optokinetic stimulation) specifies the effect of the lesion in different channels or regions of the visual pathways. Automation of perimetric procedures and continuous monitoring of fixation are important tools, enhancing the quality of examination and follow-up. The above mentioned psychophysical techniques for detection of functional defects and documentation of eventual recovery, as well as matching neuroimaging findings, are demonstrated by illustrative cases.
On nature and limits of cortical developmental plasticity after an	early lesion, in a child
Authors: Innocenti Giorgio M. , Kiper Daniel C. , Knyazeva Maria G. , Deonna Thierry W.
Published: December 2024

MS is a little girl who suffered severe, bilateral destruction of her primary visual areas at six weeks, after premature birth at 30 weeks. Between the ages of 4.5 and 5.5 years she partially recovered different aspects of visual function, and, in particular, the ability to segregate fig-ures from background, based on texture cues. The recovery might have been due to the compensatory role of the remaining visual areas that could have acquired response properties similar to those of the primary visual areas. This is not supported by the available FMRI (functional magnetic resonance imaging) responses to visual stimuli. Instead, abnormalities in the pattern of stimulus-induced changes of interhemi-spheric EEG-coherence in this patient suggest that her visual callosal connections, and possibly other cortico-cortical connections have re-organized abnormally. Since cortico-cortical connections, including the callosal ones appear to be involved in perceptual binding and figure-background segregation, their reorganization could be an important element in the functional recovery after early lesion, and/or in the residual perceptual impairment.
Reorganization in the visual cortex after retinal and cortical	damage
Authors: Eysel Ulf T. , Schweigart Georg , Mittmann Thomas , Eyding Dirk , Qu Ying , Vandesande Frans , Orban Guy , Arckens Lutgarde
Published: December 2024

Retinal and cortical lesions are completely different events that trigger visual cortical plasticity. We therefore compared the cortical effects of homonymous lesions of the central retina with effects of cortical lesions. All in vivo experiments were performed in anaesthetized, adult cats. Retinal lesions were made with a Xenon-light photocoagulator, and cortical lesions were induced by focal application of heat or ibotenic acid injection. Both, in cortical regions representing the retinal scotoma and at the border of small focal cortical lesions single neuron activity was initially suppressed and accompanied by a narrow area of increased activity adjacent to the region of functional loss during the first 1-2 weeks. At the same time an increased glutamatergic NMDA response and a reduction of GABAA and GABAB responses was observed around the cortical lesions in vitro. At an early stage long-term potentiation (LTP) is facilitated in those regions that were characterized by local upregulation of excitation and downregulation of inhibition after cortical lesions. Similarly, at the border of cortical scotomas in area 17 an increased glutamate level was found while inside the scotoma GAD levels were reduced. Shifts in topography of retinal representation as well as increases of receptive field size were detected as signs of lesion-induced neuronal reorganization after retinal and cortical lesions with longer survival times. A common cascade of events is triggered in the visual cortex by retinal as well as cortical lesions: reduced GABAergic inhibition and increased glutamatergic excitation, leading to increased spontaneous activity and visual excitability that is accompanied by facilitated LTP, and appears to initiate local cortical reorganization after functional disturbances in the visual system.
Stimulation of Schwann cell proliferation and axonal regeneration	by FK 506
Authors: Fansa Hisham , Keilhoff Gerburg , Horn Thomas , Altmann Silke , Wolf Gerald , Schneider Wolfgang
Published: December 2024

Purpose: Nerve allografts are highly antigenic and, thus, require the continuous use of immunosuppressive drugs. FK 506 was found to pre-vent rejection successfully. However, clinically neurotoxic complications have been noted in the central and peripheral nervous system although an increased rate of axonal regeneration has also been shown after nerve crush experiments. To investigate whether a possible regeneration pro-moting potency of FK 506 is determined via an influence on Schwann cells, Schwann cells were cultured from the sciatic nerve of the rat. Methods: The effect of 100 µM FK 506 administered daily on these cultures was assessed microscopically over a period of seven days and compared to an untreated control group of cultures. Additionally, the changes in intracellular calcium were recorded using a laser scanning microscope. In vivo regeneration of autologous rat sciatic nerve grafts was assessed clinically, histologically and morphometrically after two and six weeks. The animals received a daily administration of 0.6 mg FK 506/kg body weight, the control received saline. Results: In vitro FK 506 increased the Schwann cell number in culture significantly compared to non treated cultures, while the fibrocyte population was decreased. FK 506 caused a transient increase of intracellular calcium levels in cultured cells. In vivo, a significantly higher axon count was observed in the FK 506 treated grafts after two weeks regeneration compared with controls. Good regeneration was noted in all grafts after six weeks regeneration. Conclusions: The increased axon counts and decreased myelin debris in the FK 506 grafts after two weeks indicate an accelerated Wallerian degeneration and increased axon sprouting into the graft initially. The inhibition of calcineurin activity is not the mediator of the neurotrophic effect. FK 506 promotes axonal regeneration through binding to FKBP-12. The increase of intracellular calcium may induce Schwann cell pro-liferation via calmodulin. The therapeutic relevance for autologous nerve grafting, however, has to be defined in further studies.
A morphometric study of optic axons regenerated in a sciatic nerve	graft of adult rats
Authors: Chau Wai Kei , So Kwok-Fai , Tay David , Dockery Peter
Published: December 2024

Purpose: In the present study we have morphometrically examined a regeneration model in which axons normally residing in CNS have regrown and are interacting with Schwann cells from the PNS. This study will not only provide morphometric data on regenerated optic fibers but also shed light on possible factors in determining the fiber morphometry. Methods: The optic nerves of rats aged 6 weeks were cut intra-orbitally and replaced with a autologous sciatic nerve. After a survival period of 9 months, the graft or regenerated nerves containing the regenerated optic axons and Schwann cells were processed for morphometric measurements. Results: The mean myelinated axon diameter of regenerated nerve (1.8 ± 0.2 µm) was significantly (P < 0.05) greater than that of the optic nerve (0.9 ± 0.03 µm). However, unmyelinated regenerated optic axons had a smaller mean axon diameter (0.49 ± 0.04 µm) than normal myelinated optic axons. This may suggest that myelinating glial cells exert an influence on axon caliber and Schwann cells seem to have greater effect than oligodendrocytes. The mean g-ratio showing the relative myelin sheath thickness was found to be the highest in the optic nerve (0.78 ± 0.003), least in the sciatic nerve (0.6 ± 0.009) and intermediate in the regenerated nerve (0.68 ± 0.01). The results indicated that Schwann cells myelinating the regenerated optic axons have produced a thinner myelin sheath. Intra-axonally, no significant difference was detected in the number of axonal microtubules and neurofilaments between the regenerated and optic nerves. Therefore the disposition of microtubules and neurofilaments into axon may be intrinsically determined. Conclusions: In this study, we have identified some of the extrinsic and intrinsic factors in determining the fiber morphometry of the regen-erated nerve. The axon-size and myelination by glial cells were determined through the external axon-glial interactions, whereas the number of axonal microtubules and neurofilaments were intrinsically determined.
The parkinsonian toxin MPTP: action and mechanism
Authors: Przedborski Serge , Jackson-Lewis Vernice , Djaldetti Ruth , Liberatore Gabriel , Vila Miquel , Vukosavic Slobodanka , Almer Gabrielle
Published: December 2024

MPTP causes damage to substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons as seen in Parkinsons disease (PD). After sys-temic administration of MPTP, its active metabolite, MPP + , accumulates within SNpc DA neurons, where it inhibits ATP production and stim-ulates superoxide radical formation. The produced superoxide radicals react with nitric oxide (NO) to produce peroxynitrite, a highly reactive tissue-damaging species that damages proteins by oxidation and nitration. Only selected proteins appear nitrated, and among these, is found tyrosine hydroxylase (TH), the rate limiting enzyme in DA synthesis. The process of nitration inactivates TH and, consequently dopamine pro-duction. Peroxynitrite also nicks DNA, which, in turn, activates poly(ADP-ribose) polymerase (PARP). PARP activation consumes ATP, and thus acutely depletes cell energy stores. This latter event aggravates the preexisting energy failure due to MPP + -induced mitochondrial respira-tion blockade and precipitates cell death. Altogether, these findings support the view that MPTPs deleterious cascade of events include mito-chondrial respiration deficit, oxidative stress, and energy failure. Because of the similarity between the MPTP mouse model and PD, it is tempting to propose that a similar scenario applies to the pathogenesis of PD.
Uncoupling of human short and long latency stretch reflex	responses with operant conditioning
Authors: Segal Richard L. , Wolf Steven L. , Catlin Pamela A. , Gilliand Rebecca L. , Taffs Jamie K. , Bass Helen C. , Vickers Elizabeth F.
Published: December 2024

Purpose: Successful operant conditioning of the biceps brachii spinal stretch reflex (SSR) has resulted in concurrent changes in the magnitude of long latency reflex responses (LLRRs). This finding suggests a coupling of the SSR and LLRR. The purpose of the present study was to downtrain the LLRR using operant conditioning and to observe any concurrent change in the SSR. Methods: Fourteen, able-bodied, human subjects were randomly assigned to either the control group or the training group. The LLRR and SSR responses were measured as magnitude of electromyographic response to a quick stretch of the elbow flexors, delivered by a torque motor. All the subjects attended fourteen sessions. The first six sessions were baseline sessions during which no conditioning or feedback occurred. The next eight sessions were the same as the baseline sessions (extended baseline sessions) for the control group; no feedback or operant conditioning of the LLRR occurred. The next eight sessions for the training group comprised the operant conditioning. Results: Operant conditioning of the LLRR resulted in a statistically significant reduction of that response within the training group and between the two groups. Also, operant conditioning of the biceps brachii LLRR did not result in concurrent changes in the magnitude of the SSR suggesting an uncoupling of these responses. Conclusions: The LLRR of the biceps brachii could be operantly conditioned without significant changes in the SSR which suggests that these two responses can be volitionally uncoupled.
Stroke-blind for colors, faces and locations: Partial recovery	after three years
Authors: Spillmann Lothar , Laskowski Wolfgang , Lange Klaus W. , Kasper Ekkehard , Schmidt Dieter Dieter
Published: December 2024

Purpose. To study and follow-up achromatopsia, prosopagnosia, and topographagnosia in a patient who suffered a bilateral stroke of the posterior cerebral arteries. Methods. Ophthalmological, neuropsychological and neuroradiological examinations were conducted over a span of 3 years to assess the amount of brain damage and look for signs of functional recovery. Results. After the onset of achromatopsia, perception of the color green re-appeared first, followed by red, yellow, and brown. Blue which had appeared entirely black was last to return. While reading and color naming have largely recovered, color discrimination after three years remains poor especially in dim lighting. Similarly, with prosopagnosia, while the patient has learn to identify people (including photographs) by individual features, his ability to perceive and recognize faces and facial expressions holistically remains severely impaired. Recognition of streets, houses, and topographical layouts also continues to be affected, while the perception of speed and distance has somewhat improved. Perimetry further suggests a mild improvement of the superior hemianopia in his visual fields. Conclusions. Although major deficits in color, face and place perception remain, some functions impaired by the stroke have returned par-alleling a partial recovery from the brain lesion as demonstrated by NMR.
Homotopic grafts of septal neurons combined to polymeric hydrogels	placed into a fimbria-fornix lesion cavity attenuate locomotor hyperactivity	but not mnemonic dysfunctions in rats
Authors: Duconseille Elee , Carrot Sylvie-Noelle , Woerly Stephane , Kelche Christian , Will Bruno , Cassel Jean-Christophe
Published: December 2024

Purpose: We studied the behavioral effects of an intracavitary implantation of poly[N-(2-hydroxypropyl)-methacrylamidel (PHPMA) hydrogels combined to intraseptal grafts of fetal septal cell suspensions in adult female rats subjected to aspirative fimbria-fornix lesions. The hydrogels were used as substrates for bridging the lesion cavity between the septum and the hippocampus. Methods: Control groups included sham-operated or lesion-only rats, as well as lesioned rats with only the hydrogel bridge in the lesion cavity, only the graft in the septum, or an intrahippocampal graft of a septal cell suspension as a control for the standardly used ectopic transplantation strategy. Up to 10 months after grafting surgery, all rats were tested for locomotor activity in their home cage, sensorimotor performances using a beam-walking test, and cognitive performances in a radial maze, a water maze and a T-maze (rewarded alternation). Results: The lesions induced hyperlocomotion, sensorimotor disturbances and severe alterations of cognitive functions. We found that neither the grafts or the hydrogels, nor the combination of both, induced any significant enhancement of sensorimotor or cognitive performances. Nevertheless, in rats with both intraseptal (homotopic) grafts and a hydrogel implant, the locomotor activity did no longer differ from that found in sham-operated controls. Histological analysis showed that the hydrogels contained acetylcholinesterase(AChE)-positive fibers and that the hippocampal region in contact with the hydrogel exhibited AChE-positive reaction products over several hundreds of micrometers. Conclusions: These results are complementary to our previous report on electrophysiological evidence of septo-hippocampal reconnections (Duconseille et al., Rest. Neurol. Neurosci. 15, 1999, 305-317). They further suggest that septal neurons grafted homotopically and/or neurons from the host brain are able to elongate axonal processes through a PHPMA substrate up to the hippocampus. Although they did not affect the cognitive consequences of the lesion, the changes enabled by the homotopic grafts combined to the hydrogel have attenuated the lesion- induced hyperactivity.
The effects of Neotrofin™ on	septodentate sprouting after unilateral entorhinal cortex lesions in rats
Authors: Ramirez J.J. , Parakh T. , George M.N. , Freeman L. , Thomas A.A. , White C.C. , Becton A.
Published: December 2024

{\it Purpose:} Recent research on the purine derivative of hypoxanthine Neotrofin™ (4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; AIT-082) has indicated that Neotrofin treatment elevates the mRNA levels of various neurotrophic factors, including nerve growth factor (NGF), in the CNS. Several previous studies have indicated that NGF may regulate septodentate sprouting after entorhinal cortex lesions in rats. Thus, the objective of this investigation was to determine whether Neotrofin treatment would enhance lesion-induced septodentate sprouting from 4 to 15 days postlesion.

{\it Methods:} Sham-operated rats or rats with EC lesions were injected (i.p.) with either Neotrofin (30 mg/kg) or saline (0.9%) immediately after surgery and every day thereafter until the end of the treatment regimen. Septodentate sprouting, as indicated by intensity of acetylcholinesterase (AChE) label in the dentate gyrus, was assessed with optical densitometry.

{\it Results:} We observed that Neotrofin elevated the AChE-label in the outer molecular layer of the ventral dentate gyrus at 4 days postlesion and of the dorsal dentate gyrus at 15 days postlesion.

{\it Conclusions:} Neotrofin appears to have exerted limited stimulatory effects on lesion-induced sprouting by a cholinergic pathway.