Abstract Introduction/Aims There is a dearth of knowledge regarding the status of infralesional lower motor neurons (LMNs) in individuals with traumatic cervical spinal cord injury (SCI), yet there is a growing need to understand how the spinal lesion impacts LMNs caudal to the lesion epicenter, especially in the context of nerve transfer surgery to restore several key upper limb functions. Our objective was to determine the frequency of pathological spontaneous activity (PSA) at, and below, the level of spinal injury, to gain an understanding of LMN health below the spinal lesion. Methods Ninety‐one limbs in 57 individuals (53 males, mean age = 44.4 ± 16.9 years, mean duration from injury = 3.4 ± 1.4 months, 32 with motor complete injuries), were analyzed. Analysis was stratified by injury level as (1) C4 and above, (2) C5, and (3) C6‐7. Needle electromyography was performed on representative muscles innervated by the C5‐6, C6‐7, C7‐8, and C8‐T1 nerve roots. PSA was dichotomized as present or absent. Data were pooled for the most caudal infralesional segment (C8‐T1). Results A high frequency of PSA was seen in all infralesional segments. The pooled frequency of PSA for all injury levels at C8‐T1 was 68.7% of the limbs tested. There was also evidence of PSA at the rostral border of the neurological level of injury, with 58.3% of C5‐6 muscles in those with C5‐level injuries. Discussion These data support a high prevalence of infralesional LMN abnormalities following SCI, which has implications to nerve transfer candidacy, timing of the intervention, and donor nerve options.
Abstract: In vivo microdialysis was employed in order to characterize the steady‐state kinetics of the turnover of specific dopamine and serotonin metabolites in the rat striaturn 48 h after surgery. Inhibitors of monoamine oxidase (MAO; pargyline) and catechol‐O‐methyltransferase (COMT; Ro 40‐7592) were administered, either separately or in conjunction, at doses sufficient to block these enzymes in the CNS. In some experiments, the acid metabolite carrier was blocked with probenecid. Temporal changes were then observed in the efflux of interstitial dopamine, 3‐methoxytyramine (3‐MT), 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5‐hydroxyindoleacetic acid (5‐HIAA). The fractional rate constants for the accumulation or disappearance of the metabolites could be determined after pharmacological blockade of catabolic enzymes or the acid metabolite carrier. Interstitial 5‐HIAA was found to be cleared with a half‐life of approximately 2 h. After blockade of either MAO or COMT, HVA disappeared with a half‐life of 17 min. Experiments employing probenecid suggested that some of the interstitial HVA was cleared by the acid metabolite carrier, the remainder being cleared by a probenecid‐insensitive process, possibly conjugation. After MAO inhibition, DOPAC disappeared with an apparent half‐life of 11.3 min. The rate of 3‐MT accumulation after pargyline indicated that the majority of interstitial HVA (>95%) is formed from DOPAC rather than 3‐MT. The formation of 3‐MT from interstitial dopamine, calculated from the accumulation rate of 3‐MT after pargyline, appeared to follow first‐order kinetics (k = 0.1 min −1 ).
ABSTRACT Transdifferentiation is a process in which the original commitment of a cell is changed to give rise to unexpected peripheral mature cells. Our previous report showed that circulating stem cells can generate keratinocyte‐like cells (KLCs). However, it remains to be determined whether or not other peripheral blood mononuclear cells (PBMC) subsets have the potential to follow the same cell fate. In this study, the cell transdifferentiation of circulating CD14 + monocytes into KLCs and their regulatory effect on matrix metalloproteinase‐1 (MMP‐1) expression in dermal fibroblasts were evaluated. The results showed that monocytes isolated from peripheral blood mononuclear cells have the capacity to generate KLCs. These transdifferentiated cells exhibited, along with a keratinocyte‐like morphology, a characteristic profile consisting in stratifin + , cytokeratins + (types I and II), CD14 low , and involucrin + on day 21 in culture. Similar to keratinocyte‐conditioned media, KLC‐derived conditioned media were able to induce an increase in the MMP‐1 expression in dermal fibroblasts. This effect was significantly reduced by using 14‐3‐3 protein‐depleted KLC‐conditioned media. Our findings show the potential transdifferentiation of circulating CD14 + monocytes into KLCs and their regulatory effect on MMP‐1 expression in dermal fibroblasts.
Cocaine has potent pharmacological actions on a number of monoaminergic systems in the brain, including those that use noradrenaline, dopamine and serotonin as neurotransmitters. There is growing evidence that cocaine's effects on dopaminergic neurons, particularly those that make up the mesolimbic system, are closely associated with its rewarding properties. For example, low doses of dopamine receptor antagonists reliably influence cocaine self-administration, whereas noradrenaline and serotonin receptor antagonists are without consistent effects. Similarly, selective lesions of dopaminergic terminals in the nucleus accumbens, a major target of the mesolimbic dopamine projection, disrupt cocaine self-administration in a manner that is consistent with loss of cocaine-induced reward. The introduction of in vivo brain microdialysis as a tool with which to investigate the neurochemical correlates of motivated behaviour has provided new opportunities for investigating the role of dopamine in the nucleus accumbens in the acquisition and maintenance of cocaine self-administration. Although the body of literature that has been generated by this approach appears to contain some important inconsistencies, these probably reflect the use of inappropriate microdialysis conditions by some investigators. A critical review of the literature suggests that microdialysis results are generally consistent with a role for mesolimbic dopamine in cocaine-induced reward, although it does not seem to be the case that animals will work to maintain consistent increases in extracellular concentrations of dopamine in the nucleus accumbens in all experimental conditions. Elucidation of the complete neural circuitry of cocaine-induced reward remains an important priority for future research.
Lack of matrix deposition is one of the main factors that complicates the healing process of wounds. The aim of this study was to test the efficacy and safety of a liquid dermal scaffold, referred to as MeshFill (MF) that can fill the complex network of tunnels and cavities which are usually found in chronic wounds and hence improve the healing process. We evaluated in vitro and in vivo properties of a novel liquid dermal scaffold in a delayed murine full-thickness wound model. We also compared this scaffold with two commercially available granular collagen-based products (GCBP). Liquid dermal scaffold accelerated wound closure significantly compared with no-treated control and collagen-based injectable composites in a delayed splinted wound model. When we compared cellular composition and count between MF, no treatment and GCBP at the histology level, it was found that MF was the most analogous and consistent with the normal anatomy of the skin. These findings were matched with the clinical outcome observation. The flowable in situ forming scaffold is liquid at cold temperature and gels after application to the wound site. Therefore, it would conform to the topography of the wound when liquid and provides adequate tensile strength when solidified. This patient-ready gelling dermal scaffold also contains the nutritional ingredients and therefore supports cell growth. Applying an injectable liquid scaffold that can fill wound gaps and generate a matrix to promote keratinocytes and fibroblasts migration, can result in improvement of the healing process of complex wounds.
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