Stimulation of the Nucleus Basalis of Meynert Produces an Increase in the Extracellular Release of Nerve Growth Factor in the Rat Cerebral Cortex

Hotta, Harumi; Uchida, Sae; Kagitani, Fusako

doi:10.2170/physiolsci.sc008107

Cited by 25 publications

(22 citation statements)

References 30 publications

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“…13) To mimic such migration, microdialysis probes with higher MWCOs (such as 1000 kDa) could be used for probe-b in the model skin system. 23) Such increased permeability of the vessel and probe wall could cause fluid migration via the wall. As shown in Figure 4, such fluid migration can also affect drug disposition in the local area.…”

Section: Discussionmentioning

confidence: 99%

The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

Oshima

Suzuki

Yajima

et al. 2012

Biological & Pharmaceutical Bulletin

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Studies on drug disposition in inflamed skin are important for safe and effective application of topical drugs. Here, the absorption of flurbiprofen (FP) through inflamed skin was examined in vivo and in a skin-mimicking artificial model system. The model skin system consisted of a silicone membrane acting as a model stratum corneum, laminated dialysis membranes acting as a model of viable skin, and 2 microdialysis probes-one used for determination of FP concentration and one acting as a model vessel. This model system could be used for quantitative evaluation of complicated permeation processes. In the in vivo experiments, FP absorption was suppressed in rats with inflamed skin induced by an intracutaneous injection of a mixed solution of λ-carrageenan, zymosan, and casein. Bovine serum albumin solution was placed between the dialysis membranes in the model skin system to mimic protein leaching in skin; the results suggested that the delayed absorption of FP in inflamed skin was due to binding to serum proteins leaching in the tissue. Such a combination of in vivo experiments and a model skin system is useful for understanding complex phenomena in inflamed and damaged skin and reduces experimental animal use.Key words skin absorption; model skin system; inflamed skin; protein binding; flurbiprofen Although permeation through the stratum corneum is the rate-limiting step for transdermal absorption of drugs, the kinetics of drug transfer in the viable epidermis and dermis could influence the pharmacological effects of a drug systemically as well as locally. Prolonged retention of the drug in the epidermis could delay onset of the therapeutic effect and/or cause undesirable side effects in the local tissue. Binding of drugs to tissue components in the skin could relate to retention of the drugs. In the case of inflamed skin, the leaching of plasma proteins with drug-binding ability could also affect the disposition of the drugs in local tissue. 1,2) In the drug of low protein binding ratio, the effect of plasma proteins leached into the local tissue will be small, the drug of high protein binding ratio are conversely susceptible to leach of plasma proteins. Although most skin formulations are intended for sound skin without injury or inflammation, prolonged or repeated application can bring about skin inflammation; also, some topical preparations are applied specifically to treat skin with inflammation. Therefore, studies on drug disposition in inflamed skin are important for safe and effective application of topical drugs.Excised animal skin is usually used for in vitro permeation studies in the early stages of the formulation development of new products. However, in vitro experimental systems using such membranes are not suitable for evaluating the drug concentration profiles in skin because of the lack of local blood flow and physiological response.3-5) Various experimental designs, including in situ skin permeation experiments and in vitro isolated skin perfusion experiments, have been developed to study the d...

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Section: Discussionmentioning

confidence: 99%

The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

Oshima

Suzuki

Yajima

et al. 2012

Biological & Pharmaceutical Bulletin

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“…NGF protein in the culture medium was quantified using ELISA in an antibody sandwich format (NGF Emax Immunoassay System; Promega, USA) (9). The kit displays crossreactivity in several species, including rats and humans.…”

Section: Measurement Of Ngf Proteinmentioning

confidence: 99%

Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages

Miwa¹,

Lee²,

Takagishi³

et al. 2010

Biomed. Res.

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Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and α-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation.

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“…Animals were anesthetized either with halothane ( n = 12) or urethane ( n = 6) as described in our previous studies [21, 29]. The trachea of each rat was cannulated and respiration was maintained by a mechanical ventilator.…”

Section: Methodsmentioning

confidence: 99%

“…However, there are only a few studies investigating NGF secretion in vivo due to the technical challenges of these methods. Therefore, in this study, we examined whether non-noxious mechanical cutaneous stimulation promotes NGF secretion in the parietal cortex in anesthetized rats using an in vivo microdialysis method with a protein permeable probe [21]. We hypothesized that non-noxious skin stimulation promotes NGF secretion in the cerebral cortex via the activation of the NBM.…”

Section: Introductionmentioning

confidence: 99%

Non-noxious skin stimulation activates the nucleus basalis of Meynert and promotes NGF secretion in the parietal cortex via nicotinic ACh receptors

et al. 2014

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The effects of non-noxious skin stimulation on nerve growth factor (NGF) secretion in the parietal cortex were examined in anesthetized rats. Innocuous skin stimulation was delivered to the left hindlimb with a soft-hair brush. Extracellular NGF in the right parietal cortex was collected by microdialysis methods using a protein-permeable probe and was measured using an enzyme-linked immune-sorbent assay. Brushing produced a significant increase in extracellular NGF levels. This NGF response was not observed in rats pretreated with a nicotinic ACh receptor (nAChR) antagonist mecamylamine. We further examined whether brushing could activate the basal forebrain nucleus (nucleus basalis of Meynert, NBM), which is the main source of cholinergic fibers in the cerebral cortex, by means of functional MRI. The blood oxygen level-dependent signal in the right NBM was significantly higher during brushing compared to baseline. The results suggest that non-noxious skin stimulation activates NBM and promotes NGF secretion in the parietal cortex via nAChRs.

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Stimulation of the Nucleus Basalis of Meynert Produces an Increase in the Extracellular Release of Nerve Growth Factor in the Rat Cerebral Cortex

Cited by 25 publications

References 30 publications

The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages

Non-noxious skin stimulation activates the nucleus basalis of Meynert and promotes NGF secretion in the parietal cortex via nicotinic ACh receptors

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