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Dive into the research topics where Ignacio Delgado-Martinez is active.

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Featured researches published by Ignacio Delgado-Martinez.


The Journal of Neuroscience | 2007

Differential Abilities of SNAP-25 Homologs to Support Neuronal Function

Ignacio Delgado-Martinez; Ralf B. Nehring; Jakob B. Sørensen

The SNAP receptor (SNARE) complex, consisting of synaptosome-associated protein of 25 kDa (SNAP-25), synaptobrevin-2, and syntaxin-1, is involved in synaptic vesicles exocytosis. In addition, SNAP-25 has been implicated in constitutive exocytosis processes required for neurite outgrowth. However, at least three isoforms of SNAP-25 have been reported from neurons: SNAP-23, which is also present in non-neuronal cells, and the two alternative splice variants SNAP-25a and SNAP-25b. Here, we studied the differential ability of these isoforms to support the functions previously broadly ascribed to “SNAP-25.” We studied the rescue of snap-25 null neurons in culture with different SNAP-25 homologs. We find that deletion of SNAP-25 leads to strongly reduced neuron survival, and, in the few surviving cells, impaired arborization, reduced spontaneous release, and complete arrest of evoked release. Lentiviral expression of SNAP-25a, SNAP-25b, or SNAP-23 rescued neuronal survival, arborization, amplitude, and frequency of spontaneous events. Also evoked release was rescued by all isoforms, but synchronous release required SNAP-25a/b in both glutamatergic and GABAergic neurons. SNAP-23 supported asynchronous release only, reminiscent of synaptotagmin-1 null neurons. SNAP-25b was superior to SNAP-25a in vesicle priming, resembling the shift to larger releasable vesicle pools that accompanies synaptic maturation. These data demonstrate a differential ability of SNAP-25b, SNAP-25a, and SNAP-23 to support neuronal function.


Biomedical Engineering Online | 2013

Neurovascular coupling: in vivo optical techniques for functional brain imaging

Lun-De Liao; Vassiliy Tsytsarev; Ignacio Delgado-Martinez; Meng-Lin Li; Reha S. Erzurumlu; Ashwati Vipin; Josue Orellana; Yan Ren Lin; Hsin Yi Lai; You-Yin Chen; Nitish V. Thakor

Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology.


PLOS ONE | 2014

Synaptotagmin-7 Is an Asynchronous Calcium Sensor for Synaptic Transmission in Neurons Expressing SNAP-23

Jens P. Weber; Trine Lisberg Toft-Bertelsen; Ralf Mohrmann; Ignacio Delgado-Martinez; Jakob B. Sørensen

Synchronization of neurotransmitter release with the presynaptic action potential is essential for maintaining fidelity of information transfer in the central nervous system. However, synchronous release is frequently accompanied by an asynchronous release component that builds up during repetitive stimulation, and can even play a dominant role in some synapses. Here, we show that substitution of SNAP-23 for SNAP-25 in mouse autaptic glutamatergic hippocampal neurons results in asynchronous release and a higher frequency of spontaneous release events (mEPSCs). Use of neurons from double-knock-out (SNAP-25, synaptotagmin-7) mice in combination with viral transduction showed that SNAP-23-driven release is triggered by endogenous synaptotagmin-7. In the absence of synaptotagmin-7 release became even more asynchronous, and the spontaneous release rate increased even more, indicating that synaptotagmin-7 acts to synchronize release and suppress spontaneous release. However, compared to synaptotagmin-1, synaptotagmin-7 is a both leaky and asynchronous calcium sensor. In the presence of SNAP-25, consequences of the elimination of synaptotagmin-7 were small or absent, indicating that the protein pairs SNAP-25/synaptotagmin-1 and SNAP-23/synaptotagmin-7 might act as mutually exclusive calcium sensors. Expression of fusion proteins between pHluorin (pH-sensitive GFP) and synaptotagmin-1 or -7 showed that vesicles that fuse using the SNAP-23/synaptotagmin-7 combination contained synaptotagmin-1, while synaptotagmin-7 barely displayed activity-dependent trafficking between vesicle and plasma membrane, implying that it acts as a plasma membrane calcium sensor. Overall, these findings support the idea of alternative syt∶SNARE combinations driving release with different kinetics and fidelity.


Journal of Medical Devices-transactions of The Asme | 2014

Customizable Soft Pneumatic Chamber–Gripper Devices for Delicate Surgical Manipulation

Jin-Huat Low; Ignacio Delgado-Martinez; Chen-Hua Yeow

Traditional hard tissue grippers are limited in handling delicate soft tissues during surgery, particularly due to the high stress points that are generated on the soft tissue during gripping. In this study, customizable soft pneumatic chamber–gripper devices were designed to provide compliant gripping, so as to replace conventional tissue grippers such as the laparoscopic grasper or forceps in delicate tissue manipulation. The soft chamber–gripper device involves very simple design and control to generate actuation. It is fabricated from an elastomeric material using a modified soft lithography technique. The device consists of a gripper component that can be made up of one or more gripper arms with a pneumatic channel in each arm, and a chamber filled with air. The pneumatic channels are positioned close to the outer wall of the gripper arms and are connected to the chamber. Upon compression of the chamber, the pneumatic channels will inflate towards the outer walls, which thus bends the gripper arms and results in a closed gripping posture. This soft chamber–gripper device can be used to pick up objects of size up to 2 mm with a compressive force that is more than three times smaller than the grip force generated by traditional forceps. This will be useful in preventing tissue trauma during surgical manipulation, especially in nerve anastomosis. [DOI: 10.1115/1.4027688] Background


Frontiers in Neuroscience | 2016

Fascicular Topography of the Human Median Nerve for Neuroprosthetic Surgery

Ignacio Delgado-Martinez; Jordi Badia; Arán Pascual-Font; Alfonso Rodriguez-Baeza; Xavier Navarro

One of the most sought-after applications of neuroengineering is the communication between the arm and an artificial prosthetic device for the replacement of an amputated hand or the treatment of peripheral nerve injuries. For that, an electrode is placed around or inside the median nerve to serve as interface for recording and stimulation of nerve signals coming from the fascicles that innervate the muscles responsible for hand movements. Due to the lack of a standard procedure, the electrode implantation by the surgeon is strongly based on intuition, which may result in poor performance of the neuroprosthesis because of the suboptimal location of the neural interface. To provide morphological data that can aid the neuroprosthetic surgeon with this procedure, we investigated the fascicular topography of the human median nerve along the forearm and upper arm. We first performed a description of the fascicular content and branching patterns along the length of the arm. Next we built a 3D reconstruction of the median nerve so we could analyze the fascicle morphological features in relation to the arm level. Finally, we characterized the motor content of the median nerve fascicles in the upper arm. Collectively, these results indicate that fascicular organization occurs in a short segment distal to the epicondyles and remains unaltered until the muscular branches leave the main trunk. Based on our results, overall recommendations based on electrode type and implant location can be drawn to help and aid the neuroprosthetic procedure. Invasive interfaces would be more convenient for the upper arm and the most proximal third of the forearm. Epineural electrodes seem to be most suitable for the forearm segment after fascicles have been divided from the main trunk.


Journal of Neural Engineering | 2017

Fascicular nerve stimulation and recording using a novel double-aisle regenerative electrode

Ignacio Delgado-Martinez; M Righi; Daniel Santos; Annarita Cutrone; Silvia Bossi; S D’Amico; J Del Valle; Silvestro Micera; Xavier Navarro

OBJECTIVE As artificial prostheses become more refined, they are most often used as a therapeutic option for hand amputation. By contrast to extra- or intraneural interfaces, regenerative nerve electrodes are designed to enable electrical interfaces with regrowing axonal bundles of injured nerves, aiming to achieve high selectivity for recording and stimulation. However, most of the developed designs pose an obstacle to the regrowth mechanisms due to low transparency and cause impairment to the nerve regeneration. APPROACH Here we present the double-aisle electrode, a new type of highly transparent, non-obstructive regenerative electrode. Using a double-side thin-film polyimide planar multi-contact electrode, two nerve fascicles can regenerate without physical impairment through two electrically isolated aisles. MAIN RESULTS We show that this electrode can be used to selectively record and stimulate fascicles, acutely as well as chronically, and allow regeneration in nerve gaps of several millimeters without impairment. SIGNIFICANCE This multi-aisle regenerative electrode may be suitable for neuroprosthetic applications, such as prostheses, for the restoration of hand function after amputation or severe nerve injuries.


Journal of Neural Engineering | 2017

Rapid prototyping of flexible intrafascicular electrode arrays by picosecond laser structuring

Matthias Mueller; Natàlia de la Oliva; Jaume del Valle; Ignacio Delgado-Martinez; Xavier Navarro; Thomas Stieglitz

OBJECTIVE Interfacing the peripheral nervous system can be performed with a large variety of electrode arrays. However, stimulating and recording a nerve while having a reasonable amount of channels limits the number of available systems. Translational research towards human clinical trial requires device safety and biocompatibility but would benefit from design flexibility in the development process to individualize probes. APPROACH We selected established medical grade implant materials like precious metals and Parylene C to develop a rapid prototyping process for novel intrafascicular electrode arrays using a picosecond laser structuring. A design for a rodent animal model was developed in conjunction with an intrafascicular implantation strategy. Electrode characterization and optimization was performed first in saline solution in vitro before performance and biocompatibility were validated in sciatic nerves of rats in chronic implantation. MAIN RESULTS The novel fabrication process proved to be suitable for prototyping and building intrafascicular electrode arrays. Electrochemical properties of the electrode sites were enhanced and tested for long-term stability. Chronic implantation in the sciatic nerve of rats showed good biocompatibility, selectivity and stable stimulation thresholds. SIGNIFICANCE Established medical grade materials can be used for intrafascicular nerve electrode arrays when laser structuring defines structure size in the micro-scale. Design flexibility reduces re-design cycle time and material certificates are beneficial support for safety studies on the way to clinical trials.


biomedical circuits and systems conference | 2014

Neural prosthesis for motor function restoration in upper limb extremity

Sudip Nag; Kian Ann Ng; Rangarajan Jagadeesan; Swathi Sheshadri; Ignacio Delgado-Martinez; Silvia Bossi; Shih-Cheng Yen; Nitish V. Thakor

Restoration of motor function in cases of peripheral nerve injury is a challenging problem. Although peripheral nerves do regenerate, the time required for peripheral nerves to regenerate often causes atrophy to occur in the muscles before they can be re-innervated. This paper presents a solution through proximal recording of nerve signals and distal muscle stimulation. A fully implantable hardware architecture is described that can be operated by means of inductive power and MICS band data transmission schemes. Preliminary experiments and validation studies are reported with non-human primates based on recordings in the median nerve, stimulation of hand muscles, and task decoding and classification. This approach shows promise in creating a neural prosthesis capable of restoring hand movements in patients with upper limb peripheral nerve injuries.


international ieee/embs conference on neural engineering | 2015

An intrafascicular electrode with integrated amplifiers for peripheral nerve recording

Kian Ann Ng; Annarita Cutrone; Silvia Bossi; Sudip Nag; Ignacio Delgado-Martinez; Swathi Sheshadri; Claire A. Poulard; Yong Ping Xu; Shih-Cheng Yen; Nitish V. Thakor

Thin-film longitudinal intrafascicular electrodes (tf-LIFE) are widely used for peripheral nerve recordings. tf-LIFEs are also promising electrodes for neural signal acquisition in future peripheral nerve prostheses. However, common mode signal interference, and electrical artifacts originating from long wire leads and wire movement are known problems encountered when using such electrodes, which lead to degradation in the recording quality. Here, we report an active tf-LIFE electrode implemented by integrating a neural amplifier chip die in close proximity to a tf-LIFE electrode. Consuming only 1mW and measuring 37 mm×7.2 mm×2.4 mm, this active tf-LIFE electrode creates a reliable connection and considerably shortens the distance between the electrode site and neural amplifier. This active electrode has demonstrated repeatable in-vivo recordings of compound action potentials from the rat sciatic nerve. Our results show that this electrode is suitable for repeated in-vivo recordings of compound action potentials from nerves in applications such as peripheral and visceral nerve interfaces that require low-noise stable nerve recordings.


Journal of Tissue Engineering and Regenerative Medicine | 2018

Segregation of motor and sensory axons regenerating through bicompartmental tubes by combining extracellular matrix components with neurotrophic factors

Jaume del Valle; Daniel Santos; Ignacio Delgado-Martinez; Natàlia de la Oliva; Guido Giudetti; Silvestro Micera; Xavier Navarro

Segregation of regenerating motor and sensory axons may be a good strategy to improve selective functionality of regenerative interfaces to provide closed‐loop commands. Provided that extracellular matrix components and neurotrophic factors exert guidance effects on different neuronal populations, we assessed in vivo the potential of separating sensory and motor axons regenerating in a bicompartmental Y‐type tube, with each branch prefilled with an adequate combination of extracellular matrix and neurotrophic factors.

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Nitish V. Thakor

National University of Singapore

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Shih-Cheng Yen

National University of Singapore

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Swathi Sheshadri

National University of Singapore

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Xavier Navarro

Autonomous University of Barcelona

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Silvia Bossi

Sant'Anna School of Advanced Studies

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Annarita Cutrone

Sant'Anna School of Advanced Studies

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Kian Ann Ng

National University of Singapore

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Sudip Nag

National University of Singapore

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