Subarachnoid Space of the CNS, Nasal Mucosa, and Lymphatic System

Jackson, Richard T.; Tigges, Johannes; Arnold, W.

doi:10.1001/archotol.1979.00790160014003

Cited by 132 publications

(69 citation statements)

References 18 publications

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“…This has been shown among others for dihydroergotamine (Wang et al 1998), cocaine (Chow et al 1999), lidocaine (Chou & Donovan 1998) and cefalexin (Sakane et al 1991). The extracellular pathway, that transports polar drugs through tight junctions (see Epithelial cell barrier above) between sustentacular cells and olfactory neurons into the CSF, relies on a direct anatomic connection between the submucosa and the subarachnoid extensions, the perineural space surrounding the olfactory nerves, as they penetrate the cribriform plate ( Figure 6) (Jackson et al 1979). The drug is thought to enter the perineural space either through loosely adherent perineural epithelium surrounding the axon (``open-cuff model''), or to enter through the epithelial cell junctions if the perineural epithelium is closely adherent to the axon (``closed-cuff model'').…”

Section: Transport Pathwaysmentioning

confidence: 76%

Is nose-to-brain transport of drugs in man a reality?

Illum¹

2004

Journal of Pharmacy and Pharmacology

397

262

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The blood-brain barrier that segregates the brain interstitial fluid from the circulating blood provides an efficient barrier for the diffusion of most, especially polar, drugs from the blood to receptors in the central nervous system (CNS). Hence limitations are evident in the treatment of CNS diseases, such as Parkinson's and Alzheimer's diseases, especially exploiting neuropeptides and similar polar and large molecular weight drugs. In recent years interest has been expressed in the use of the nasal route for delivery of drugs to the brain, exploiting the olfactory pathway. A wealth of studies has reported proof of nose-to-brain delivery of a range of different drugs in animal models, such as the rat. Studies in man have mostly compared the pharmacological effects (e.g. brain functions) of nasally applied drugs with parenterally applied drugs and have shown a distinct indication of direct nose-to-brain transport. Recent studies in volunteers involving cerebrospinal fluid sampling, blood sampling and pharmacokinetic analysis after nasal, and in some instances parenteral administration of different drugs, have in my opinion confirmed the likely existence of a direct pathway from nose to brain.

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Section: Transport Pathwaysmentioning

confidence: 76%

Is nose-to-brain transport of drugs in man a reality?

Illum¹

2004

Journal of Pharmacy and Pharmacology

397

262

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“…According to previous studies (12,13,23,60), the perineurial cells abutting the olfactory fascicles at the level of ethmoidal lamina cribrosa are an extension of the meninges which pass through the foramina and surround the traversing fila olfactoria (Fig. 5).…”

Section: Using Immunofluorescence For Prpmentioning

confidence: 88%

Olfactory System Involvement in Natural Scrapie Disease

Corona

Porcario

Martucci

et al. 2009

J Virol

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The olfactory system (OS) is involved in many infectious and neurodegenerative diseases, both human and animal, and it has recently been investigated in regard to transmissible spongiform encephalopathies. Previous assessments of nasal mucosa infection by prions following intracerebral challenge suggested a potential centrifugal spread along the olfactory nerve fibers of the pathological prion protein (PrP Sc ). Whether the nasal cavity may be a route for centripetal prion infection to the brain has also been experimentally studied. With the present study, we wanted to determine whether prion deposition in the OS occurs also under

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“…Scientists attempted to find out the mechanism of such clearance [115] [116]. In particular, drainage via the neighborhood of facial nerves was therefore investigated.…”

Section: Endeavor To Understand Pathways For Lymphatic Drainage Of Csmentioning

confidence: 99%

The Integrative Five-Fluid Circulation System in the Human Body

Fung¹,

Kong²

2016

OJMIP

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Water is the key medium to transport numerous constituents and to provide a platform for physiological processes to take place in the living organisms in general; it also participates actively in many of these processes. In humans, there are different vehicles to contain water and its constituents. Our objective is to find out whether there is an overall water-base circulation system in the human body by analyzing the updated findings of different research groups on the physiological functions of various seemingly isolated fluid systems. By 1963, there were five separate fluid systems discovered in mammalians: (i) The Primo Vasculature Fluid (PVF) with protein precursors and micro cells held in the Primo Vasculature System (PVS). (ii) Blood with its constituents held in the cardio vasculature. (iii) Extracranial interstitial fluid (ISF) whose vehicle had a very irregular structure-the interstitium all over the body. (iv) The cerebrospinal fluid had been considered to be within the brain ventricles and spinal canal. (v) The extra-cranial lymphatic system which drained ISF, and had been known to join the subclavian vein. Fluid (i) was first reported in 1963 and fluids (ii) to (v) have been known for many decades, but the failure to detect a lymphatic system inside the skull has also been a mystery for many decades. The intra-cranial ISF (which we name as BISF) has drawn little attention, apart from discussing the mechanism of the blood-brain-barrier. During the past decade, there has been direct evidence indicating that CSF and BISF are actually mixed. After that, the intracranial lymphatic system was discovered and confirmed in animal models only slightly over one year back, and we called such fluid as glymphatic-fluid. After reviewing the stated "classical" five fluid systems together with the new findings in Sections 2 -7, we propose, for the first time, that the PVF, the blood, ISF, a mixture of CSF-BISF, and a mixture of glymphatic-fluid and lymph form an integrative circulation system in water base in the human and other mammalian bodies, as schematically represented in the last section. In this paper, we point out the positive correlation of chronic neuro degenerative diseases such as Alzheimer's disease, Parkinson's diseases and the insufficient brain wastes clearance by the glymphatic system. We also discuss the role played by the venous vessels as part of such clearance in upright posture. Moreover, simple non-invasive maneuver techniques are introduced here, as one example of enhancement of glymphatic fluid flow out of the skull to join the lymphatic system. A series of questions are raised in Section 8, the answers to which would help us to understand the transition from physio-to pathological states in the development of many diseases. Detailed analysis of this paper leads us to consider that research in understanding this integrative circulation system is only at the infancy stage, and fluid dynamics investigation seems to be the plausible modality of approach in the near future.

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Subarachnoid Space of the CNS, Nasal Mucosa, and Lymphatic System

Cited by 132 publications

References 18 publications

Is nose-to-brain transport of drugs in man a reality?

Is nose-to-brain transport of drugs in man a reality?

Olfactory System Involvement in Natural Scrapie Disease

The Integrative Five-Fluid Circulation System in the Human Body

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