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B. R. Botterman

Bio: B. R. Botterman is an academic researcher from University of Texas Southwestern Medical Center. The author has contributed to research in topics: Motor unit & Reflex. The author has an hindex of 23, co-authored 39 publications receiving 2702 citations. Previous affiliations of B. R. Botterman include University of Arizona & Drexel University.

Papers
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Journal ArticleDOI
TL;DR: Carbon nanotube-coated electrodes are expected to improve current electrophysiological techniques and to facilitate the development of long-lasting brain-machine interface devices.
Abstract: Implanting electrical devices in the nervous system to treat neural diseases is becoming very common. The success of these brain-machine interfaces depends on the electrodes that come into contact with the neural tissue. Here we show that conventional tungsten and stainless steel wire electrodes can be coated with carbon nanotubes using electrochemical techniques under ambient conditions. The carbon nanotube coating enhanced both recording and electrical stimulation of neurons in culture, rats and monkeys by decreasing the electrode impedance and increasing charge transfer. Carbon nanotube-coated electrodes are expected to improve current electrophysiological techniques and to facilitate the development of long-lasting brain-machine interface devices.

665 citations

Journal ArticleDOI
TL;DR: A role for TNF is demonstrated in vitro and in vivo in two models of PD, and the possibility that delaying the progressive degeneration of the nigrostriatal pathway in humans is therapeutically feasible with agents capable of blocking solTNF in early stages of PD is raised.
Abstract: The mechanisms that trigger or contribute to loss of dopaminergic (DA) neurons in Parkinson's disease (PD) remain unclear and controversial. Elevated levels of tumor necrosis factor (TNF) in CSF and postmortem brains of PD patients and animal models of PD implicate this proinflammatory cytokine in the pathophysiology of the disease; but a role for TNF in mediating loss of DA neurons in PD has not been clearly demonstrated. Here, we report that neutralization of soluble TNF (solTNF) in vivo with the engineered dominant-negative TNF compound XENP345 (a PEGylated version of the TNF variant A145R/I97T) reduced by 50% the retrograde nigral degeneration induced by a striatal injection of the oxidative neurotoxin 6-hydroxydopamine (6-OHDA). XENP345 was neuroprotective only when infused into the nigra, not the striatum. XENP345/6-OHDA rats displayed attenuated amphetamine-induced rotational behavior, indicating preservation of striatal dopamine levels. Similar protective effects were observed with chronic in vivo coinfusion of XENP345 with bacterial lipopolysaccharide (LPS) into the substantia nigra, confirming a role for solTNF-dependent neuroinflammation in nigral degeneration. In embryonic rat midbrain neuron/glia cell cultures exposed to LPS, even delayed administration of XENP345 prevented selective degeneration of DA neurons despite sustained microglia activation and secretion of solTNF. XENP345 also attenuated 6-OHDA-induced DA neuron toxicity in vitro. Collectively, our data demonstrate a role for TNF in vitro and in vivo in two models of PD, and raise the possibility that delaying the progressive degeneration of the nigrostriatal pathway in humans is therapeutically feasible with agents capable of blocking solTNF in early stages of PD.

346 citations

Journal ArticleDOI
TL;DR: Consideration of the functional anatomy of the association between motor units and muscle receptors suggests the need for detailed structural-functional analyses of those muscles with specializations in architecture, fiber-type composition and distribution, and in the number and distribution of their muscle spindles and tendon organs.
Abstract: Muscle spindles and tendon organs occur in most somatic muscles of the mammal and are particularly concentrated in muscles subserving fine movements, including postural muscles and small muscles of the distal extremities. In those mixed muscles in which the different fiber and motor unit types are “compartmentalized,” the spindles, and perhaps tendon organs also, are virtually limited to those compartments predominated by “oxidative” muscle fibers. These morphological observations based on a broad array of muscles in many species, complement electrophysiological studies which have emphasized that (1) the “oxidative” motor units have low reflex thresholds and (2) segmental proprioceptive reflexes may be primarily concerned with the control of finely graded contractions. Consideration of the functional anatomy of the association between motor units and muscle receptors suggests the need for detailed structural-functional analyses of those muscles with specializations in architecture, fiber-type composition and distribution, and in the number and distribution of their muscle spindles and tendon organs. An electrophysiological analysis of the relationship between the spinal cord and such muscles might also reveal certain strategies and mechanisms underlying segmental motor control which are either absent or obscured in the analysis of that select number of “homogenously-mixed” muscles conventionally used in the study of the mammalian segmental motor control system.

289 citations

Journal ArticleDOI
TL;DR: Analysis of cell location in the spinal cord and rostro‐caudal differences in group I volley sizes gave evidence of a topographic organization of the biceps femoris motor nucleus which could contribute to the observed localization of monosynaptic Ia excitatory post‐synaptic potentials.
Abstract: Evidence is presented for the existence of a localization of monosynaptic Ia excitatory post-synaptic potentials (e.p.s.p.s) in the motor nucleus of a cat hind limb muscle. Intracellular recordings from biceps femoris motoneurones were made in anaesthetized low spinal cats of the effects of stimuli to the nerve branches supplying the anterior, middle, and posterior portions of the biceps femoris muscle. Recordings were also made during stimulation of nerves to semimembranosus and semitendinosus in order to provide a means of categorizing middle biceps cells as 'extensors' (middle biceps-extensor; i.e. like anterior biceps cells) or as 'flexors' (middle biceps-flexor; like posterior biceps). Homonymous nerve-branch (i.e. from anterior, middle or posterior biceps) monosynaptic Ia e.p.s.p.s were compared within unifunctional (flexor or extensor) groups of motoneurones. In three of four comparisons (anterior biceps nerve branch onto anterior and middle biceps-extensor cells, middle biceps onto middle biceps-flexor and posterior biceps, posterior biceps onto middle biceps-flexor and posterior biceps) the anterior, middle and posterior biceps nerve branches contributed larger e.p.s.p.s to their 'own' motoneurones than to motoneurones supplying other 'compartments' of the muscle. In the fourth case, middle biceps's input appeared to have similar effects onto anterior biceps and middle biceps-extensor cells. A normalization was performed to eliminate the possibility that the differences in e.p.s.p. sizes were due to differences in cell type within the four cell groupings (i.e. differences in the number of cells supplying FF, F(int.), FR and S muscle units). This normalization confirmed that the localization in the first three comparisons was not a consequence of differences in motoneurone type and, in addition, suggested that middle biceps may indeed have greater effects on middle biceps-extensor than anterior biceps cells. In addition to the asymmetrical effects of anterior and middle biceps nerve branches onto anterior biceps and middle biceps-extensor motoneurones, it was shown that while semitendinosus and posterior biceps contributed larger e.p.s.p.s to middle biceps-flexor than to middle biceps-extensor cells, the anterior biceps nerve branch and semimembranosus nerve contributed equally to the two middle biceps groups. Analysis of cell location in the spinal cord and rostro-caudal differences in group I volley sizes gave evidence of a topographic organization of the biceps femoris motor nucleus which could contribute to the observed localization. However, localization was also evident when comparing e.p.s.p. amplitudes in pairs of neighbouring cells of different category, indicating a role for neuronal recognition factors.

127 citations


Cited by
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Journal ArticleDOI
01 Feb 2013-Science
TL;DR: Although not yet providing compelling mechanical strength or electrical or thermal conductivities for many applications, CNT yarns and sheets already have promising performance for applications including supercapacitors, actuators, and lightweight electromagnetic shields.
Abstract: Worldwide commercial interest in carbon nanotubes (CNTs) is reflected in a production capacity that presently exceeds several thousand tons per year. Currently, bulk CNT powders are incorporated in diverse commercial products ranging from rechargeable batteries, automotive parts, and sporting goods to boat hulls and water filters. Advances in CNT synthesis, purification, and chemical modification are enabling integration of CNTs in thin-film electronics and large-area coatings. Although not yet providing compelling mechanical strength or electrical or thermal conductivities for many applications, CNT yarns and sheets already have promising performance for applications including supercapacitors, actuators, and lightweight electromagnetic shields.

4,596 citations

Journal ArticleDOI
TL;DR: Overall, available data support the importance of non-cell-autonomous pathological mechanisms in Parkinson's disease, which are mostly mediated by activated glial and peripheral immune cells.
Abstract: Parkinson's disease is characterised by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. Despite intensive research, the cause of the neuronal loss in Parkinson's disease is poorly understood. Neuroinflammatory mechanisms might contribute to the cascade of events leading to neuronal degeneration. In this Review, we describe the evidence for neuroinflammatory processes from post-mortem and in vivo studies in Parkinson's disease. We further identify the cellular and molecular events associated with neuroinflammation that are involved in the degeneration of dopaminergic neurons in animal models of the disease. Overall, available data support the importance of non-cell-autonomous pathological mechanisms in Parkinson's disease, which are mostly mediated by activated glial and peripheral immune cells. This cellular response to neurodegeneration triggers deleterious events (eg, oxidative stress and cytokine-receptor-mediated apoptosis), which might eventually lead to dopaminergic cell death and hence disease progression. Finally, we highlight possible therapeutic strategies (including immunomodulatory drugs and therapeutic immunisation) aimed at downregulating these inflammatory processes that might be important to slow the progression of Parkinson's disease.

1,627 citations

Journal ArticleDOI
TL;DR: This review will focus on the role of the main cytokines, chemokines, and their receptors in the pathophysiology of auto-inflammatory disorders, pro- inflammatory disorders, and neurological disorders involving inflammation.

1,485 citations

Journal ArticleDOI
TL;DR: This work proposes four themes that provide a basis for the systematic evaluation of the neural and neuromuscular fatigue mechanisms and suggests a number of experiments to advance the understanding of the neurobiology of muscle fatigue.
Abstract: Muscle fatigue encompasses a class of acute effects that impair motor performance. The mechanisms that can produce fatigue involve all elements of the motor system, from a failure of the formulation of the descending drive provided by suprasegmental centers to a reduction in the activity of the contractile proteins. We propose four themes that provide a basis for the systematic evaluation of the neural and neuromuscular fatigue mechanisms: 1) task dependency to identify the conditions that activate the various mechanisms; 2) force-fatigability relationship to explore the interaction between the mechanisms that results in a hyperbolic relationship between force and endurance time; 3) muscle wisdom to examine the association among a concurrent decline in force, relaxation rate, and motor neuron discharge that results in an optimization of force; and 4) sense of effort to determine the role of effort in the impairment of performance. On the basis of this perspective with an emphasis on neural mechanisms, we suggest a number of experiments to advance our understanding of the neurobiology of muscle fatigue.

1,391 citations

Journal ArticleDOI
TL;DR: The nanocomposite nature of the extracellular matrix is reviewed, the design considerations for different tissues are described, and the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues are discussed.
Abstract: Tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development. Here we review the nanocomposite nature of the extracellular matrix, describe the design considerations for different tissues and discuss the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues. We also examine the different nanodevices used to trigger certain processes for tissue development, and offer our view on the principal challenges and prospects of applying nanotechnology in tissue engineering.

1,272 citations