Abraham Martín

Abraham Martín
Achucarro Basque Center for Neuroscience · Neuroimaging and Biomarkers of Inflammation

PhD

About

73
Publications
11,691
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1,791
Citations
Citations since 2017
26 Research Items
1046 Citations
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2017201820192020202120222023050100150200
2017201820192020202120222023050100150200

Publications

Publications (73)
Article
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Background and objective: The determination of pharmacokinetic properties of new chemical entities is a key step in the process of drug development. Positron emission tomography (PET) is an ideal technique to obtain both biodistribution and pharmacokinetic parameters of new compounds over a wide range of chemical modalities. Here, we use a multi-ra...
Article
Purpose: Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [18F]SF6 as a positron emission tomography (PET) venti...
Article
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Background Validation of new biomarkers of Alzheimer disease (AD) is crucial for the successful development and implementation of treatment strategies. Additional to traditional AT(N) biomarkers, neuroinflammation biomarkers, such as translocator protein (TSPO) and cystine/glutamine antiporter system (x c ⁻ ), could be considered when assessing AD...
Article
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The status of serotonin 5­HT2A receptors (5­HT2ARs) in schizophrenia has been controversial. In vivo positron emission tomography neuroimaging and in vitro post-mortem binding studies have reported conflicting results about 5­HT2AR density. Radiotracers bind different receptor conformations depending on their agonist, antagonist or inverse agonist...
Article
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Purpose: The increase in butyrylcholinesterase (BChE) activity in the brain of Alzheimer disease (AD) patients and animal models of AD position this enzyme as a potential biomarker of the disease. However, the information on the ability of BChE to serve as AD biomarker is contradicting, also due to scarce longitudinal studies of BChE activity abund...
Article
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Fluorinated nanoparticles have increasing applications, but they are still challenging to prepare, especially in the case of water-soluble fluorinated nanoparticles. Herein, a fluorine labeling strategy is presented that is based on the conjugation of custom-made small fluorinated building blocks, obtained by simple synthetic transformations, with...
Article
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Adenosine A1 receptors (A1ARs) are promising imaging biomarkers and targets for the treatment of stroke. Nevertheless, the role of A1ARs on ischemic damage and its subsequent neuroinflammatory response has been scarcely explored so far. Methods: In this study, the expression of A1ARs after transient middle cerebral artery occlusion (MCAO) was evalu...
Article
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In vivo positron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far. In vivo and ex vivo assessment of gliogenesis after transient middle cerebral artery occlusi...
Article
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It is well settled that the amyloidogenic properties of the plasma protein transporter transthyretin (TTR) can be modulated by compounds that stabilize its native tetrameric conformation. TTR is also present in cerebrospinal fluid where it can bind to Aβ-peptides and prevent Aβ aggregation. We have previously shown that treatment of Alzheimer’s Dis...
Article
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Crossed cerebellar diaschisis (CCD) is a decrease of regional blood flow and metabolism in the cerebellar hemisphere contralateral to the injured brain hemisphere as a common consequence of stroke. Despite CCD has been detected in patients with stroke using neuroimaging modalities, the evaluation of this phenomenon in rodent models of cerebral isch...
Article
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Microglia survey the brain microenvironment for signals of injury or infection and are essential for the initiation and resolution of pathogen- or tissue damage-induced inflammation. Understanding the mechanism of microglia responses during pathology is hence vital to promote regenerative responses. Here, we analyzed the role of purinergic receptor...
Article
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The inflammatory response is a major factor in stroke pathophysiology and contributes to secondary neuronal damage in both acute and chronic stages of the ischemic injury. Recent work in experimental cerebral ischemia has demonstrated the involvement of neurotransmitter signaling in the modulation of neuroinflammation. The present review discusses...
Article
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In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and...
Article
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The original version of this Article contained an error in the spelling of the author Álvaro Sebastián-Serrano, which was incorrectly given as Álvaro Sebastián Serrano. This has now been corrected in both the PDF and HTML versions of the Article.
Article
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Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactiv...
Article
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Background: In vivo positron-emission tomography (PET) imaging of transporter protein (TSPO) expression is an attractive and indispensable tool for the diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia. Despite several radiotracers have shown an excellent capacity to image neuroinflammation, novel radiotracers such as [...
Article
Background and aims: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid recep...
Article
Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using Positron Emission Tomography (PET) imaging. In this work, we report the evaluat...
Chapter
Acute brain damage after stroke produces remarkable changes in the brain that can be visualized with a variety of neuroimaging techniques. Some of these techniques are used in patients for diagnostic purposes and are now available to image the rodent brain. However, non-invasive imaging of the brain of rodents is challenging because of the size of...
Article
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Purpose: Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc(-) activity and its connec...
Article
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In vivo Positron Emission Tomography (PET) imaging of the cystine-glutamate antiporter (system xc⁻) activity with [¹⁸F]FSPG is meant to be an attractive tool for the diagnosis and therapy evaluation of brain diseases. However, the role of system xc⁻ in cerebral ischemia and its involvement in inflammatory reaction has been scarcely explored. In thi...
Article
Introduction: Following MCAo, tissue outcome varies depending on depth and duration of hypoperfusion and efficiency of reperfusion. However, the precise time-course of these events in relation to tissue and behavioral outcome remains unsettled due to lack of a wide field-of-view quantitative imaging technique able to map perfusion in the rodent bra...
Article
The influence of toll-like receptor 4 on neurogenesis and inflammation has been scarcely explored so far by using neuroimaging techniques. For this purpose, we performed magnetic resonance imaging and positron emission tomography with 3′-deoxy-3′-[18F]fluorothymidine and [11C]PK11195 at 2, 7, and 14 days following cerebral ischemia in TLR4+/+ and T...
Article
The influence of Toll-Like Receptor 4 (TLR4) on neurogenesis and inflammation has been scarcely explored so far by using neuroimaging techniques. For this purpose, we performed magnetic resonance imaging (MRI) and positron emission tomography (PET) with [18F]FLT and [11C]PK11195 at 2, 7 and 14 days following cerebral ischemia in TLR4+/+ and TLR4-/-...
Article
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Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensiona...
Article
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PET imaging of nicotinic acetylcholine receptors (nAChRs) could become an effective tool for the diagnosis and therapy evaluation of neurologic diseases. Despite this, the role of nAChRs α4β2 receptors after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. To investigate this, we perfor...
Chapter
Positron emission tomography (PET) is an imaging technique able to provide detailed spatial-temporal functional data of the cerebral neurotransmission system. The dopaminergic pathway has been largely characterized with PET imaging due to the existence of large number of radiotracers available to bind to the different targets of this system. Thus,...
Chapter
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Positron emission tomography (PET) is an imaging technique able to provide detailed spatial-temporal functional data of the cerebral neurotransmission system. The dopaminergic pathway has been largely characterized with PET imaging due to the existence of large number of radiotracers available to bind to the different targets of this system. Thus,...
Article
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During brain ischemia, an excessive release of glutamate triggers neuronal death through the overactivation of NMDA receptors (NMDARs); however, the underlying pathways that alter glutamate homeostasis and whether synaptic or extrasynaptic sites are responsible for excess glutamate remain controversial. Here, we monitored ischemia-gated currents in...
Article
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Aging, a time-dependent functional decline of biological processes, is the primary risk factor in developing diseases such as cancer, cardiovascular or degenerative diseases. There is a real need to understand the human aging process in order to increase the length of disease-free life, also known as "health span". Accumulation of progerin and prel...
Article
Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers because of their hydrophobic character, spherical structure, and excellent chemical and photochemical stability. In the present paper, the synthesis and in vivo evaluation of (11) C-labeled (1,7-dicarba-c...
Article
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Microglia, the resident immune cells of the central nervous system, responds to brain disarrangements by becoming activated to contend with brain damage. Here we show that the expression of P2X4 receptors is upregulated in inflammatory foci and in activated microglia in the spinal cord of rats with experimental autoimmune encephalomyelitis (EAE) as...
Article
A simple and straightforward method is presented for the direct proton beam activation of 18O-enriched titanium dioxide nanoparticles (TiO2 NPs) via the 18O(p,n)18F nuclear reaction in order to assess the biological fate of the NPs using positron emission tomography (PET). The radiolabeling of the NPs does not alter their morphological properties a...
Article
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PURPOSE: The aim of the present study was to develop short half-lived tools for in vitro and in vivo β-amyloid imaging in mice, for which no suitable PET tracers are available. PROCEDURES: Five 13N-labelled azo compounds (1-5) were synthesized using a three-step process using cyclotron-produced [13N]NO3 -. Biodistribution studies were performed u...
Article
The aim of the present study was to develop short half-lived tools for in vitro and in vivo β-amyloid imaging in mice, for which no suitable PET tracers are available. Five (13)N-labelled azo compounds (1-5) were synthesized using a three-step process using cyclotron-produced [(13)N]NO3 (-). Biodistribution studies were performed using positron emi...
Article
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The aim of the present study was to evaluate the use of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats. Healthy, male Sprague-Dawley rats (n = 30) were divided in two groups of 15 animals each. Animals from one group (n...
Article
The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging a...
Article
Full-text available
The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging a...
Article
Hemeoxygenase (HO) is an enzymatic system that degrades heme. HO-1 is an inducible isoform whereas HO-2 is constitutive. Stroke strongly induces HO-1 expression but the underlying mechanisms are not fully elucidated. Cytokines that are up-regulated after ischemia, like IL-10, can induce HO-1 gene expression, which is positively regulated by the tra...
Article
The extraordinary small size of NPs makes them difficult to detect and quantify once distributed in a material or biological system. We present a simple and straight forward method for the direct proton beam activation of synthetic or commercially available aluminium oxide NPs (Al2O3 NPs ) via the 16O(p,α)13N nuclear reaction in order to assess the...
Article
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The precise biologic mechanisms involved in functional recovery processes in response to stroke such as dopaminergic neurotransmission are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(11)C]raclopride at 1,...
Article
The synthesis of (18)F-labelled positron emitting NPs by direct irradiation of (18)O-enriched aluminum oxide NPs with 16 MeV protons is reported. Biodistribution studies of the labelled particles after intravenous administration were performed in male rats using positron emission tomography. The simple and general activation strategy can be applied...
Article
The biodistribution pattern of [(11)C]Kendine 91 (a novel HDAC inhibitor) after IV administration has been evaluated using Positron Emission Tomography (rats) and gamma counting of dissected tissues (rats and mice) at different doses (1 μg/kg and 10.0 mg/kg). Metabolism in mice plasma has been also investigated by radio-HPLC. Obtained results (fast...
Article
It is well known that after cerebral ischemia, brain suffers blood flow changes over time that have been correlated with inflammation, angiogenesis and functional recovery processes. Nevertheless, post-ischemic spatiotemporal changes of brain perfusion have not been fully investigated to date. Here we tested whether PET with [¹³N]ammonia would evid...
Article
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Blood flow interruption in a cerebral artery causes brain ischemia and induces dramatic changes of perfusion and metabolism in the corresponding territory. We performed in parallel positron emission tomography (PET) with [(15)O]H(2)O, single photon emission computed tomography (SPECT) with [(99m)Tc]hexamethylpropylene-amino-oxime ([(99m)Tc]HMPAO) a...
Article
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There is controversy over whether matrix metalloproteinases (MMPs) are activated during the early therapeutic window following ischemic stroke. Ex vivo, an increase was reported as early as 4 hours, whereas in vivo, no increase was found until 24 hours postischemia. We used fluorescence diffuse optical tomography to image MMP activity following exp...
Article
Positron emission tomography (PET) studies in humans have used (11)C-flumazenil (FMZ) to assess neuronal viability after stroke. Here we aimed to study whether (11)C-FMZ binding was sensitive to neuronal damage in the acute phase following ischemia/reperfusion in the rat brain. Transient (2 h followed by reperfusion) and permanent intraluminal midd...
Article
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Many new candidate pharmaceuticals designed to improve recovery after stroke have been proposed recently, but there are still too few molecular imaging methods capable to assess their efficacy. A hallmark of the inflammatory reaction that follows focal cerebral ischemia is overexpression of the mitochondrial peripheral benzodiazepine receptor/18 kD...
Conference Paper
Shear Wave Imaging (SWI) is an ultrasound based technique for elasticity imaging that has been successfully tested on several organs in the framework of cancer diagnosis. In this work, the potential of this technique to map brain elasticity in vivo on trepanned small animals is investigated. From a SWI scan of the rat brain, 3D elasticity maps are...
Article
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Inflammatory responses are closely associated with many neurologic disorders and influence their outcome. In vivo imaging can document events accompanying neuroinflammation, such as changes in blood flow, vascular permeability, tightness of the blood-to-brain barrier, local metabolic activity, and expression of specific molecular targets. Here, we...
Article
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Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document infla...
Article
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Glucose consumption is severely depressed in the ischemic core, whereas it is maintained or even increased in penumbral regions during ischemia. Conversely, glucose utilization is severely reduced early after reperfusion in spite that glucose and oxygen are available. Experimental studies suggest that glucose hypometabolism might be an early predic...
Article
Sodium pyruvate has shown protective effects in various experimental models of brain ischemia. The main holdup of this drug is that most of the benefits are reported with a very narrow time window for intervention. Here we investigated whether pyruvate could protect the brain against ischemic damage using a model of 2-hour middle cerebral artery oc...
Article
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[(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We perform...
Article
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Stroke induces a strong inflammatory reaction in the brain and depresses the immune system. We sought to assess longitudinal changes in T-cell numbers in the lymphoid organs of living mice after brain ischemia. Middle cerebral artery occlusion was carried out in transgenic mice expressing green fluorescent protein (GFP+) in the T-cell population un...
Article
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Transient focal cerebral ischemia in the rat alters vessel properties, and spontaneously hypertensive rats (SHR) show a poorer outcome after ischemia. In the present study we examined the role of hypertension on vessel properties after ischemia-reperfusion. The right middle cerebral artery (MCA) was occluded (90 min) and reperfused (24 h) in SHR (n...
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