Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. METHODS: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. RESULTS: Statistically significant differences were found between groups in heart rate using the Kruskal-Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. CONCLUSIONS: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? OBJECTIVE: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. METHODS: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. RESULTS: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. CONCLUSIONS: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Model-based control structure design of a full-scale WWTP under the retrofitting process.

The anoxic-oxic (A/O) municipal wastewater treatment plant (WWTP) of Manresa (Catalonia, Spain) was studied for a possible conversion to an anaerobic/anoxic/oxic (A2/O) configuration to promote enhanced biological phosphorus removal. The control structure had to be redesigned to satisfy the new necessity to control phosphorus concentration, besides ammonium and nitrate concentrations (main pollutant concentrations). Thereby, decentralized control structures with proportional-integral-derivative (PID) controllers and centralized control structures with model-predictive controllers (MPC) were designed and tested. All the designed control structures had their performance systematically tested regarding effluent quality and operating costs. The centralized control structure, A2/O-3-MPC, achieved the lowest operating costs with the best effluent quality using the A2/O plant configuration for the Manresa WWTP. The controlled variables used in this control structure were ammonium in the effluent, nitrate at the end of the anoxic zone and phosphate at the end of the anaerobic zone, while the manipulated variables were the internal and external recycle flow rates and the dissolved oxygen setpoint in the aerobic reactors.

Startup and long-term performance of biotrickling filters packed with polyurethane foam and poplar wood chips treating a mixture of ethylmercaptan, H2S, and NH3.

UNLABELLED: Treatment of a mixture of NH3, H2S, and ethylmercaptan (EM) was investigated for more than 15 months in two biotrickling filters packed with poplar wood chips and polyurethane foam. Inlet loads ranging from 5 to 10 g N-NH3 m-3 hr-1, from 5 to 16 g S-H2S m-3 hr-1, and from 0 to 5 g EM m-3 hr-1 were applied. During startup, the biotrickling filter packed with polyurethane foam was re-inoculated due to reduced biomass retention as well as a stronger effect of nitrogen compounds inhibition compared with the biotrickling filter packed with poplar wood. Accurate pH control between 7 and 7.5 favored pollutants abatement. In the long run, complete NH3 removal in the gas phase was achieved in both reactors, while H2S removal efficiencies exceeded 90%. EM abatement was significantly different in both reactors. A systematically lower elimination capacity was found in the polyurethane foam bioreactor. N fractions in the liquid phase proved that high nitrification rates were reached throughout steady-state operation in both bioreactors. CO2 production showed the extent of the organic packing material degradation, which allowed estimating its service lifetime in around 2 years. In the long run, the bioreactor packed with the organic packing material had a lower stability. However, an economic analysis indicated that poplar wood chips are a competitive alternative to inorganic packing materials in biotrickling filters. IMPLICATIONS: We provide new insights in the use of organic packing materials in biotrickling filters for the treatment of H2S, NH3, and mercaptans and compare them with polyurethane foam, a packing commonly used in biotrickling filters. We found interesting features related with the startup of the reactors and parameterized both the performance under steady-state conditions and the influence of the gas contact time. We provide relevant conclusions in the profitability of organic packing materials under a biotrickling filter configuration, which is infrequent but proven reliable from our research results. The report is useful to designers and users of this technology.

Technical and economic analysis of real anaerobic digester centrate by means of partial nitrification and sustainable heterotrophic denitrification.

The reliability of partial nitrification coupled with heterotrophic denitrification for the treatment of real anaerobic digester centrate produced in a wastewater treatment plant was technically and economically assessed in two sequencing batch reactors. Removal efficiencies above 90% were consistently achieved at N-ammonium loads above 1.2 g N L⁻¹ d⁻¹. Ethanol, affluent from a waste water treatment plant (biological treatment inlet) and a zero-cost liquid residue from a chemical industry containing polyethylene glycol and sorbitol were employed as carbon source for denitrification. In this last case, a total organic carbon (TOC) requirement of 4.5 g TOC g⁻¹ NO2⁻-N was calculated. The denitrification rate was 0.26 g NO2⁻-N g VSS⁻¹ d⁻¹ (VSS: volatile suspended solids). These results show that a carbon-rich waste can serve as a no-cost feed for denitrifying bioreactors. An in-depth economic analysis considering the main investment and operating costs of the process was developed, showing that it can suppose yearly savings above 50% with respect to the most widely used alternative of returning anaerobic digester centrate untreated to the head of the facility.

[Safe use of magnetic resonance imaging: practical recommendations for personnel]. / Utilización segura de la resonancia magnética. Recomendaciones prácticas para el personal que trabaja con resonancia magnética.

MRI is a powerful diagnostic imaging tool and its use has increased significantly in hospitals all over the world. Due to the technical particularities of MRI, all staff members dealing with the scanner need to have adequate knowledge of how it works and of aspects related to safety. The European parliament and council's directive on minimum health and safety requirements for workers dealing with electromagnetic fields (EMF) 2004/40/CE represents a threat to the clinical development and healthcare use of MRI. The efforts of the Alliance for MRI led to a postponement of the European parliament's decision, first until April 2012 and finally until October 2013. The purpose of this article is to define and propose a set of practical rules to ensure the protection of workers involved with MRI scanners. It also aims to define our position with respect to UE directive (2004/40/CE).

The role of ketamine in major depressive disorders: Effects on parvalbumin-positive interneurons in hippocampus.

Major depressive disorder (MDD) is a complex illness that is arising as a growing public health concern. Although several brain areas are related to this type of disorders, at the cellular level, the parvalbumin-positive cells of the hippocampus interplay a very relevant role. They control pyramidal cell bursts, neuronal networks, basic microcircuit functions, and other complex neuronal tasks involved in mood disorders. In resistant depressions, the efficacy of current antidepressant treatments drops dramatically, so the new rapid-acting antidepressants (RAADs) are being postulated as novel treatments. Ketamine at subanesthetic doses and its derivative metabolites have been proposed as RAADs due to their rapid and sustained action by blocking N-methyl-d-aspartate (NMDA) receptors, which in turn lead to the release of brain-derived neurotrophic factor (BDNF). This mechanism produces a rapid plasticity activation mediated by neurotransmitter homeostasis, synapse recovery, and increased dendritic spines and therefore, it is a promising therapeutic approach to improve cognitive symptoms in MDD.

Management of incidental durotomies in an integrated Orthopaedic and Neurosurgical Spinal Unit.

Introduction: Incidental durotomy (ID) is an intraoperative event associated to prolonged bed rest and hospital stay, antibiotic use, higher patient dissatisfaction, and leg pain among other complications of its postoperative course. Several repair techniques and postsurgical care have been proposed for its management. This study was designed to develop an agreed protocol in cases of ID among Orthopaedic Surgeons (OS) and Neurosurgeons (NS) integrated into a Spinal Surgery Unit. Research question: Incidental durotomies management protocol. Materials and methods: From 997 eligible cases operated in Hospital del Mar (Barcelona, Spain) from April 2018 to March 2022, demographic, clinical, surgical and postoperative data was collected for statistical analysis from the morbidity and mortality database, with 79 identified IDs. Redo procedures were significantly associated to OS, and cervical and anterior/lateral approaches to NS, both groups were not comparable. Results: ID occurred in 7.9% of cases, more frequently after the lockdown (p=0.03), in females (p=0.04), during posterior approaches (p=0.003), and less frequently in the cervical spine (p=0.009). IDs were linked to postoperative infections (p< 0.001) and nerve root damage (p< 0.001). Patients without ID evolved more satisfactorily during the postoperative period (p=0.002), and those with CSF leak (20/79) spent on bed rest more than twice the time as those without (p<0.001). Multivariable logistic regression showed strong association between posterior approaches and ID, between complicated postoperative courses and ID. Discussion and conclusions: ID is linked to an adverse postoperative recovery, and it should be primarily repaired under microscope, with early mobilization of patients after surgery.

Interaction between sorption and biodegradation in a biofilter packed with activated carbon.

The main objective of this study is to evaluate qualitatively and quantitatively the effect of starvation periods in the biodegradation capacity of microorganisms when the support media is a material with high sorption capacity. Pollutant sorption and biodegradation, which occur simultaneously in the biofilter, describe the overall behavior of the air treatment system during normal operation and during starvation periods. Results obtained in the present study demonstrate that sorption capacity of the material not only plays an important role during the start-up of operation, but it is also important during steady operation. Simultaneously, as biomass grows on the support, biodegradation becomes more decisive in the performance. It was found that zones of packing material with low moisture content are controlled by the sorption mechanism, at the expense of biodegradation, and they are essential as a pollutant reservoir during starvation periods. In the present study a significant decrease in the biodegradation capacity of microorganisms immobilized on activated carbon was not observed as a consequence of continuous load interruptions.

Effects of VEGF administration or neutralization on the BBB of developing rat brain.

We investigated the effects of exogenous Vascular Endothelial Growth Factor VEGF combined with an enriched environment on BBB integrity after a minimal trauma induced during the first days of the critical visual period in rats, when peak levels of endogenous VEGF secretion are reached. VEGF was administered using osmotic mini-pumps placed in middle cortical layers of P18 Long-Evansrats. Tissue changes were evaluated using conventional histology. BBB integrity was shown by immunohistochemistry techniques for EBA and GluT-1. Mini-pump implantation produced a wider cavity in anti-VEGF infused rats. In VEGF-infused rats there was a damaged region around the cannula that was smaller in rats raised in an enriched environment (EE). The administration of VEGF induced a high concentration of plasma proteins in the neuropil around the point of cannula placement and a high inflammatory reaction. VEGF-infused rats raised in an EE showed a lower degree of extravasation and better tissue preservation. Anti-VEGF administration produced a lower protein expression profile and more widespread deterioration of tissue. Double immunofluorescence for EBA and GluT-1 showed that the administration of VEGF preserves the tissue, which remains present but not fully functional. In contrast, a combination of VEGF administration and an EE partially protects the functionally damaged tissue with a higher preservation of BBB integrity.

The role of eNOS in vascular permeability in ENU-induced gliomas.

Brain edema in gliomas is an epiphenomenon related to blood-brain-barrier (BBB) breakdown in which endothelial nitric oxide synthase (eNOS) plays a key role. When induced by vascular endothelial growth factor (VEGF), eNOS synthesizes nitric oxide that increases vascular permeability. We investigated the relationship between eNOS, VEGF and BBB dysfunction in experimental gliomas.Tumors were produced in Sprague-Dawley rats by transplacentary administration of Ethylnitrosourea (ENU). Immunoexpression of eNOS and VEGF(165) was studied to identify locations of vascular permeability. BBB permeability was evaluated using gadolinium and intravital dyes and BBB integrity by endothelial barrier antigen (EBA), glucose transporter-1 (GluT-1) and occludin immunostaining. Low grade gliomas displayed constitutive eNOS expression in endothelial cells and in VEGF-positive astrocytes surrounding vessels. Malignant gliomas overexpressed eNOS in aberrant vessels and displayed numerous adjacent reactive astrocytes positive for VEGF. Huge dilated vessels inside tumors and glomeruloid vessels on the periphery of the tumor showed strong immunopositivity for eNOS and a lack of occludin and EBA staining in several vascular sections. BBB dysfunction on these aberrant vessels caused increased permeability as shown by Gadolinium contrast enhancement and intravital dye extravasation.These findings support the central role of eNOS in intra- and peritumoral edema in ENU-induced gliomas.

[Neuroimaging: technical aspects and practice]. / Neuroimagen: Fundamentos técnicos y prácticos.

Neuroimaging using both functional and structural examinations like positron emission tomography (PET), single photon emission tomography (SPECT), computed tomography (CT) and magnetic nuclear imaging (MRI) provide supportive information of great importance for the diagnosis and treatment of patients with central nervous system disorders. Therefore, they have become commonplace in clinical practice and basic biomedical research. In recent years we have seen the development of multimodality equipment that enables PET or SPECT to be combined with a CT structural image. Moreover, experimental equipment combining PET and MRI has now been developed. Additionally, methodological features that provide a higher image quality, and analysis tools for objective quantification and interpretation have been refined. This article reviews the technical aspects of those imaging methods, highlighting the most significant and recent advances in the development of neuroimaging.

Feasibility of S-rich streams valorization through a two-step biosulfur production process.

A bioscrubbing process named SONOVA has been developed, tested and assessed herein to valorize flue gases containing SOx. The process consists in a first scrubbing stage, to absorb and oxidize SO2 to sulfate, followed by a two-step biological stage. It consists of (1) an up-flow anaerobic sludge (UASB) reactor to reduce sulfate to sulfide with crude glycerol and (2) a continuous stirred tank reactor (CSTR) to partially oxidize sulfide to elemental sulfur (S0). SONOVA integrates the reutilization of resources, using the effluent of the biological stage as a sorbent agent and the residual heat of flue gases to dry the product. S0 is then obtained as a value-added product, which nowadays is produced from fossil fuels. In this research, SO2 concentrations up to 4000 ppmv were absorbed in 2 s of gas contact time in the spray-scrubber with removal efficiencies above 80%. The UASB reduced up to 9.3 kg S-Sulfate m-3 d-1 with sulfide productivities of 6 kg S m-3 d-1 at an hydraulic retention time (HRT) as low as 2 h. Finally, CSTR was fed with the UASB effluent and operated at HRT ranging from 12 h to 4 h without biomass wash-out. Sulfide was fully oxidized to S0 with a productivity of 2.3 kg S m-3 d-1 at the lowest HRT tested. Overall, this research has explored not only maximum capabilities of each SONOVA stage but has also assessed the interactions between the different units, which opens up the possibility of recovering S0 from harmful SOx emissions, optimizing resources utilization and costs.

Distal biceps tendon rupture: diagnostic strength of ultrasonography and magnetic resonance. / Rotura del tendón distal del bíceps: potencia diagnóstica de la ecografía y la resonancia magnética.

OBJECTIVE: The main purpose of this study is to determine the agreement between two radiological tests, ultrasonography and magnetic resonance, in the diagnosis of distal brachial biceps tendon injury. MATERIAL AND METHOD: A retrospective study was made of patients over 3 years who underwent distal brachial biceps tendon reattachment open surgery, and whose preoperative diagnosis was complemented either by ultrasonography, by magnetic resonance or both. The agreement was calculated by Cohen's kappa coefficient (k). RESULTS: Information of 79 patients was analyzed. The concordance was excellent between resonance and surgical findings (k=.950), and a good Cohen's kappa coefficient was also achieved between both ultrasonography and surgery (k=.706) and between information of sonography and magnetic resonance (k=.667). CONCLUSIONS: Resonance and ultrasonography could be considered reliable diagnostic tests to determine the acute rupture of the distal brachial biceps tendon in patients with consistent aetiology and physical examination.

Economical assessment of the design, construction and operation of open-bed biofilters for waste gas treatment.

A protocol was developed with the purpose of assessing the main costs implied in the set-up, operation and maintenance of a waste gas-treating conventional biofilter. The main operating parameters considered in the protocol were the empty bed residence time and the gas flow rate. A wide variety of investment and operating costs were considered. In order to check its reliability, the protocol was applied to a number of scenarios, with biofilter volumes ranging from 8.3 to 4000 m(3). Results show that total annualized costs were between 20,000 and 220,000 euro/year and directly dependent, among other factors, on the size of the system. Total investment and operating costs for average-size compost biofilters were around 60,000 euro and 20,000 euro/year, respectively, which are concordant with actual costs. Also, a sensitivity analysis was performed in order to assess the relative influence of a series of selected costs. Results prove that operating costs are those that influence the total annual costs to a higher extent. Also, packing material replacement costs contribute significantly to the total yearly costs in biofilters with a volume higher than 800 m(3). Among operating costs, the electricity consumption is the main influencing factor in biofilters with a gas flow rate above 50,000 m(3)/h, while labor costs are critical at lower gas flow rates. In addition, the use of a variety of packing materials commonly employed in biofiltration was assessed. According to the results obtained, special attention should be paid to the packing material selected, as it is the main parameter influencing the medium replacement costs, and one of the main factors affecting investment costs.

Exploring the performance limits of a sulfidogenic UASB during the long-term use of crude glycerol as electron donor.

SOx contained in flue gases and S-rich liquid effluents can be valorized to recover elemental sulfur in a two-stage bioscrubbing process. The reduction of sulfate to sulfide is the most crucial stage to be optimized. In this study, the long-term performance of an up-flow anaerobic sludge blanket (UASB) reactor using crude glycerol as electron donor was assessed. The UASB was operated for 400 days with different sulfate and organic loading rates (SLR and OLR, respectively) and a COD/S-SO42- ratio ranging from 3.8 g O2 g-1 S to 5.4 g O2 g-1 S. After inoculation with methanogenic, granular biomass, the competition between sulfate-reducing and methanogenic microorganisms determined to what extent dissolved sulfide and methane were produced. After the complete washout of methanogens, which was revealed by next-generation sequencing analysis, the highest S-EC was reached in the system. The highest average sulfate elimination capacity (S-EC = 4.3 kg S m-3d-1) was obtained at a COD/S-SO42- ratio of 5.4 g O2 g-1 S and an OLR of 24.4 kg O2 m-3d-1 with a sulfate removal efficiency of 94%. The conversion of influent COD to methane decreased from 12% to 2.5% as the SLR increased while a large fraction of acetate (35% of the initial COD) was accumulated. Our data indicate that crude glycerol can promote sulfidogenesis. However, the disappearance of methanogens in the long-term due to the out competition by sulfate reducing bacteria, lead to such large accumulation of acetate.

On-line titrimetric monitoring of anaerobic-anoxic EBPR processes.

Denitrifying phosphorus accumulating organisms (DPAO) are able to remove nitrogen and phosphorus simultaneously. The use of DPAO in EBPR systems results in a substantial saving on aeration cost and a lower sludge production when compared to anaerobic-aerobic EBPR systems. This process is usually studied in sequencing batch reactors (SBR) and monitored with off-line measurements. However, off-line monitoring implies low frequency data sampling and delay between sampling and obtainment of the results. For this reason, an online measurement such as titrimetry is strongly recommended to improve the daily management of the lab-scale SBR. This paper shows different applications of titrimetric measurements for on-line monitoring of DPAO lab-scale SBR cycles. The results demonstrate that titrimetry is a suitable tool for detecting the end of phosphorus release and carbon substrate depletion point in the anaerobic phase. Moreover, this paper proposes the indirect measurement of nitrate/nitrite uptake rate with titrimetric measurements, which allows the on-line estimation of its concentration during the anoxic phase. Therefore, titrimetry is an on-line measurement with a high potential to implement new control strategies in DPAO lab-scale SBR systems.

Screening of biological sulfate reduction conditions for sulfidogenesis promotion using a methanogenic granular sludge.

Effluents containing great amounts of oxidized sulfur compounds, such as sulfate or sulfite, can be valorized as elemental sulfur from a sequential reduction-oxidation biological process. However, the most important, challenging step to be optimized is the reduction of sulfate. The present study aimed at seeking out the optimal conditions to promote sulfidogenesis instead of methanogenesis using waste carbon sources and a methanogenic granular sludge. Crude glycerol showed better results in terms of the consumed COD/S-Sulfate ratio compared with acetate, cheese whey, pig slurry, and vinasse. Then, the screening of several conditions (T, pH, and COD/S-Sulfate ratio) and the effects of air presence and dissolved sulfide inhibition on sulfate reduction was carried out. Sulfidogenesis was promoted at 35 °C, pH = 8.5, COD/S-Sulfate ratio above 7.0 g O2 g-1 S, microaerophilic conditions, and dissolved sulfide concentrations below 250 mg S2- L-1. These conditions were tested for nearly 3 months in the startup and operation of a 2 L UASB reactor. An inlet sulfate concentration of 220 mg S L-1 and an HRT of 2 h were set. Removal efficiencies of approximately 90% were obtained with less than 20% of organic matter destined for biogas production.

Deleterious Effects of VEGFR2 and RET Inhibition in a Preclinical Model of Parkinson's Disease.

Neurotrophic factors (NTFs) are a promising therapeutic option for Parkinson's disease (PD). They exert their function through tyrosine kinase receptors. Our goal was to assess the effects of administering a selective tyrosine kinase inhibitor (vandetanib) that blocks VEGFR2 and RET receptors in a preclinical model of PD. Rats underwent intrastriatal injections of 6-hydroxydopamine (6-OHDA). Two weeks later, the rats received 30 mg/kg vandetanib or saline orally. The effects were assessed using the rotational behavioral test, tyrosine hydroxylase (TH) immunohistochemistry, and western blot. In 6-OHDA-lesioned rats, motor symptoms were almost undetectable, but morphological and biochemical changes were significant. Vandetanib treatment, combined with the presence of 6-OHDA lesions, significantly increased behavioral impairment and morphological and biochemical changes. Therefore, after vandetanib treatment, the TH-immunopositive striatal volume, the percentage of TH+ neurons, and the extent of the axodendritic network in the substantia nigra decreased. Glial fibrillary acidic protein-positivity significantly decreased in the striatum and substantia nigra in the vandetanib-treated group. In addition, p-Akt and p-ERK 1/2 levels were significantly lower and caspase-3 expression significantly increased after vandetanib administration. In conclusion, we demonstrate for the first time the deleterious effect of a tyrosine kinase inhibitor on the dopaminergic system, supporting the beneficial and synergistic effect of NTFs reported in previous papers.