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1.
CNS Neurol Disord Drug Targets ; 17(10): 743-756, 2018.
Article in English | MEDLINE | ID: mdl-30179148

ABSTRACT

BACKGROUND & OBJECTIVE: Regulation of composition, volume and turnover of fluids surrounding the brain and damp cells is vital. These fluids transport all substances required for cells and remove the unwanted materials. This regulation tends to act as barrier to prevent free exchange of materials between the brain and blood. There are specific mechanisms concerned with fluid secretion of the controlled composition of the brain, and others responsible for reabsorption eventually to blood and the extracellular fluid whatever their composition is. The current view assumes that choroidal plexuses secrete the major part of Cerebrospinal Fluid (CSF), while the Blood-Brain Barrier (BBB) has a much less contribution to fluid production, generating Interstitial Fluid (ISF) that drains to CSF. The skull is a rigid box; thereby the sum of volumes occupied by the parenchyma with its ISF, related connective tissue, the vasculature, the meninges and the CSF must be relatively constant according to the Monroe-Kellie dogma. This constitutes a formidable challenge that normal organisms surpass daily. The ISF and CSF provide water and solutes influx and efflux from cells to these targeted fluids in a quite precise way. Microvessels within the parenchyma are sufficiently close to every cell where diffusion areas for solutes are tiny. Despite this, CSF and ISF exhibit very similar compositions, but differ significantly from blood plasma. Many hydrophilic substances are effectively prevented from the entry into the brain via blood, while others like neurotransmitters are extremely hindered from getting out of the brain. Anatomical principle of the barrier and routes of fluid transfer cannot explain the extraordinary accuracy of fluids and substances needed to enter or leave the brain firmly. There is one aspect that has not been deeply analyzed, despite being prevalent in all the above processes, it is considered a part of the CSF and ISF dynamics. This aspect is the energy necessary to propel them properly in time, form, space, quantity and temporality. CONCLUSION: The recent hypothesis based on glucose and ATP as sources of energy presents numerous contradictions and controversies. The discovery of the unsuspected intrinsic ability of melanin to dissociate and reform water molecules, similar to the role of chlorophyll in plants, was confirmed in the study of ISF and CSF biology.


Subject(s)
Biological Transport/physiology , Blood-Brain Barrier/physiology , Brain/physiology , Cerebrospinal Fluid/metabolism , Melanins/metabolism , Water-Electrolyte Balance/physiology , Animals , Brain Edema/cerebrospinal fluid , Brain Edema/metabolism , Choroid Plexus/metabolism , Choroid Plexus/ultrastructure , Homeostasis , Humans , Melanins/chemistry
2.
CNS Neurol Disord Drug Targets ; 15(2): 135-40, 2016.
Article in English | MEDLINE | ID: mdl-26831264

ABSTRACT

Retinal adhesion mechanisms in mammals are quite complex and multifactorial in nature. To date, these mechanisms are incompletely understood due to a variety of chemical, physical, and physiological forces impinging upon retinal tissue: retinal pigment epithelium, nearby tissues as sclera and vitreous, the subretinal space, and the highly complex interphotoreceptor matrix that fills subretinal space. The adhesion of the retina to the choroid, rather than anatomical, is a dynamic process, as the retina detaches a few minutes after life ceases. The adhesion mechanisms described in the literature, such as intraocular pressure and the oncotic pressure of the choroid that seems to push the retina towards the choroid, the delicate anatomical relationships between the rod and cone photoreceptors, the retinal pigment epithelium, the existence of a complex material called interphotoreceptor matrix, as well as other metabolic and structural factors, still cannot explain the remarkable features observed in the adhesion mechanisms between the photoreceptor layer and retinal pigment epithelium cells. The unexpected intrinsic property of melanin to absorb light energy and transform it into chemically based free energy can explain normal adhesion of the sensory retina to the pigment epithelium. In this article, we explore and highlight this explanation, which states that it is definitely able to provide a new treatment avenue against devastating neurodegenerative properties.


Subject(s)
Central Nervous System Diseases/metabolism , Melanins/metabolism , Melanins/therapeutic use , Retina/metabolism , Water/metabolism , Animals , Central Nervous System Diseases/drug therapy , Humans , Melanins/pharmacology , Retina/drug effects , Treatment Outcome
3.
CNS Neurol Disord Drug Targets ; 14(9): 1235-42, 2015.
Article in English | MEDLINE | ID: mdl-26295828

ABSTRACT

One of the biggest problems and challenges for the development of new drugs and treatment strategies against Alzheimer Disease (AD) is the crossing of target drugs into the blood brain barrier. The use of nanoparticles in drug delivery therapy holds much promise in targeting remote tissues, and as a result many studies have attempted to study the ultrastructural localization of nanoparticles in various tissues. However, there are currently no in vivo studies demonstrating the ultrastructural distribution of nanoparticles in the brain. The aim of this study was to address how intraperitoneal injection of silver nanoparticles in the brain leads to leaking on the inter-endothelial contact and luminal plasma membrane, thus elucidating the possibility of penetrating into the most affected areas in the Alzheimer brain (vascular endothelium, perivascular, neuronal and glial cells). Our results show that the silver nanoparticles reached the brain and were found in hippocampal areas, indicating that they can be conjugated and used to deliver the drugs into the cell cytoplasm of the damaged brain cells. The present study can be useful for the development of novel drug delivering therapy and useful in understanding the delivery, distribution and effects of silver nanoparticles in AD brain tissue at cellular and subcellular level.


Subject(s)
Alzheimer Disease/drug therapy , Brain/drug effects , Drug Delivery Systems/methods , Metal Nanoparticles , Neuroprotective Agents/administration & dosage , Silver Compounds , Alzheimer Disease/pathology , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/ultrastructure , Brain/blood supply , Brain/ultrastructure , Female , Injections, Intraperitoneal , Male , Microscopy, Electron , Microvessels/drug effects , Microvessels/ultrastructure , Models, Animal , Neurons/drug effects , Neurons/ultrastructure , Rats, Wistar
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