Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs - from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns - specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of SCI should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic spinal cord-injured patients

Anxiolytics may promote locomotor function recovery in spinal cord injury patients

Recent findings in animal models of paraplegia suggest that specific nonbenzodiazepine anxiolytics may temporarily restore locomotor functions after spinal cord injury (SCI). Experiments using in vitro models have revealed, indeed, that selective serotonin receptor (5-HTR) ligands such as 5-HTR1A agonists, known as relatively safe anxiolytics, can acutely elicit episodes of rhythmic neuronal activity refered to as fictive locomotion in isolated spinal cord preparations. Along the same line, in vivo studies have recently shown that this subclass of anxiolytics can induce, shortly after systemic administration (eg, orally or subcutaneously), some locomotor-like hindlimb movements during 45–60 minutes in completely spinal cord-transected (Tx) rodents. Using ‘knock-out’ mice (eg, 5-HTR7-/-) and selective antagonists, it has been clearly established that both 5-HTR1A and 5-HTR7 were critically involved in mediating the pro-locomotor effects induced by 8-OH-DPAT (typically referred to as a 5-HTR1A agonist) in Tx animals. Taken together, these in vitro and in vivo data strongly support the idea that 5-HTR1A agonists may eventually become constitutive elements of a novel first-in-class combinatorial treatment aimed at periodically inducing short episodes of treadmill stepping in SCI patients

CCRS proposal for evaluating LANDSAT-D MSS and TM data

Accomplishments in the evaluation of LANDSAT 4 data are reported. The objectives of the Canadian proposal are: (1) to quantify the LANDSAT-4 sensors and system performance for the purpose of updating the radiometric and geometric correction algorithms for MSS and for developing and evaluating new correction algorithms to be used for TM data processing; (2) to compare and access the degree to which LANDSAT-4 MSS data can be integrated with MSS imagery acquired from earlier LANDSAT missions; and (3) to apply image analysis and information extraction techniques for specific user applications such as forestry or agriculture

Multilevel Analysis of Locomotion in Immature Preparations Suggests Innovative Strategies to Reactivate Stepping after Spinal Cord Injury

Locomotion is one of the most complex motor behaviors. Locomotor patterns change during early life, reflecting development of numerous peripheral and hierarchically organized central structures. Among them, the spinal cord is of particular interest since it houses the central pattern generator (CPG) for locomotion. This main command center is capable of eliciting and coordinating complex series of rhythmic neural signals sent to motoneurons and to corresponding target-muscles for basic locomotor activity. For a long-time, the CPG has been considered a black box. In recent years, complementary insights from in vitro and in vivo animal models have contributed significantly to a better understanding of its constituents, properties and ways to recover locomotion after a spinal cord injury (SCI). This review discusses key findings made by comparing the results of in vitro isolated spinal cord preparations and spinal-transected in vivo models from neonatal animals. Pharmacological, electrical, and sensory stimulation approaches largely used to further understand CPG function may also soon become therapeutic tools for potent CPG reactivation and locomotor movement induction in persons with SCI or developmental neuromuscular disorder

Is Propanediol a safer molecule than some other glycols in personal care and anti-aging biocosmeceutical products?

Propanediol (1,3-propanediol) is an ingredient increasingly used by the industry for electronic cigarettes, personal care creams and anti-aging serums among many other products. For some skin care purposes, it is used to enhance the transdermal absorption of other ingredients (e.g., the actives) enabling moisturizing effects and skin smoothness to be improved. Propanediol may be derived from corn although synthetic forms also exist. It is a chemical similar to other glycols such as propylene glycol (1,2-propanediol) but generally believed to be safer. This short communication reveals in fact that only limited scientific evidence of safety is available. Preliminary signs of toxicity have been found following administration of propanediol in humans although its dose-dependent toxicity and long-term side effects on health have not been significantly explored. Consequently, as of today, skin care and anti-aging products for elderly, a vulnerable population, should not automatically be considered as safe. Those comprising 1,3-propanediol should probably be used with caution until scientifically-proven safety data for the intended purposes are obtained by independent scientists

Are self-consciousness and mindfulness altered by aging?

It is well known that aging is the process of becoming older. It is also associated normally with a progressive loss of biological functions – both physical and mental –, underlied by naturally-occurring changes at the molecular level that may lead to the development of so-called aging-related health problems – e.g., Parkinson’s Disease, dementia, memory loss, cerebrovascular problems and Alzheimer’s Disease. Along this idea, a fundamental question remains – are self-consciousness and mindfulness also affected by these physiological or pathophysiological changes? This short article summarizes briefly some of the key sementic, conceptual, methodological and physiological issues that shall be addressed prior to tentatively providing answers to comparable questions

Amplification of Adipogenic Commitment by VSTM2A

Despite progress in our comprehension of the mechanisms regulating adipose tissue development, the nature of the factors that functionally characterize adipose precursors is still elusive. Defining the early steps regulating adipocyte development is needed for the generation of tools to control adipose tissue size and function. Here, we report the discovery of V-set and transmembrane domain containing 2A (VSTM2A) as a protein expressed and secreted by committed preadipocytes. VSTM2A expression is elevated in the early phases of adipogenesis in vitro and adipose tissue development in vivo. We show that VSTM2A-producing cells associate with the vasculature and express the common surface markers of adipocyte progenitors. Overexpression of VSTM2A induces adipogenesis, whereas its depletion impairs this process. VSTM2A controls preadipocyte determination at least in part by modulating BMP signaling and PPARgamma2 activation. We propose a model in which VSTM2A is produced to preserve and amplify the adipogenic capability of adipose precursors

Exact Foldy-Wouthuysen transformation for spin 0 particle in curved space

Up to now, the only known exact Foldy- Wouthuysen transformation (FWT) in curved space is that concerning Dirac particles coupled to static spacetime metrics. Here we construct the exact FWT related to a real spin-0 particle for the aforementioned spacetimes. This exact transformation exists independently of the value of the coupling between the scalar field and gravity. Moreover, the gravitational Darwin term written for the conformal coupling is one third of the relevant term in the fermionic case.Comment: 10 pages, revtex, improved version to appear in Phys. Rev.