Blood–Central Nervous System Barriers: The Gateway to Neurodegeneration, Neuroprotection and Neuroregeneration

Sharma, Hari Shanker

doi:10.1007/978-0-387-30375-8_17

Cited by 21 publications

(13 citation statements)

References 260 publications

(389 reference statements)

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“…Since the blood-brain barrier (BBB) strictly maintains the fluid microenvironment of the central nervous system (CNS), a possibility exists that long-term SD could affect BBB function [21][22][23][24][25][26]. Previous reports from our laboratory showed that stressors affect brain function by inducing a selective BBB breakdown that is instrumental in provoking neuronal cell injury [27][28][29][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron

Sharma

Mureșanu²,

Lafuente

et al. 2015

Mol Neurobiol

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Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB disruption and brain pathology, (ii) nanoparticles exacerbate SD-induced brain damage, and (iii) serotonin 5-HT3 receptor antagonist ondansetron is neuroprotective in SD that is further potentiated byTiO2-nanowired delivery, not reported earlier.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron

Sharma

Mureșanu²,

Lafuente

et al. 2015

Mol Neurobiol

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“…On the other hand, we consider the BBB “disrupted” if Evans blue (EB) or albumins are extravasated into brain or spinal cord parenchyma. BBB “disruption” or “breakdown” represents a long-term opening associated with often-irreversible phenomena [80–82]. …”

Section: Bbb and Bscb In Chronic Pain: “To Be Or Not To Be” Permeamentioning

confidence: 99%

Neurovascular Unit in Chronic Pain

Radu

Bramantı

Osculati

et al. 2013

Mediators of Inflammation

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Chronic pain is a debilitating condition with major socioeconomic impact, whose neurobiological basis is still not clear. An involvement of the neurovascular unit (NVU) has been recently proposed. In particular, the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB), two NVU key players, may be affected during the development of chronic pain; in particular, transient permeabilization of the barrier is suggested by several inflammatory- and nerve-injury-based pain models, and we argue that the clarification of molecular BBB/BSCB permeabilization events will shed new light in understanding chronic pain mechanisms. Possible biases in experiments supporting this theory and its translational potentials are discussed. Moving beyond an exclusive focus on the role of the endothelium, we propose that our understanding of the mechanisms subserving chronic pain will benefit from the extension of research efforts to the NVU as a whole. In this view, the available evidence on the interaction between analgesic drugs and the NVU is here reviewed. Chronic pain comorbidities, such as neuroinflammatory and neurodegenerative diseases, are also discussed in view of NVU changes, together with innovative pharmacological solutions targeting NVU components in chronic pain treatment.

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“…The anatomical site of the BBB is largely located within the cerebral endothelial cells that are connected with tight junctions (Figure 1). Because of presence of tight junctions between endothelial cells the cerebral endothelium behaves like and extended plasma membrane 18,19. Thus, only those substances could enter into the brain that are lipid soluble and/or may diffuse freely across the cell membrane 18,22,23.…”

Section: Blood–brain Barrier Regulates Drug Entry Into the Brainmentioning

confidence: 99%

“…However, a clear proof or lack of it is still unknown and require further investigations. For details see Refs 18–20. (Reprinted with permission from Ref 18.…”

Section: Blood–brain Barrier Regulates Drug Entry Into the Brainmentioning

confidence: 99%

Nanowired drug delivery for neuroprotection in central nervous system injuries: modulation by environmental temperature, intoxication of nanoparticles, and comorbidity factors

Sharma

2011

WIREs Nanomed Nanobiotechnol

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Recent developments in nanomedicine resulted in targeted drug delivery of active compounds into the central nervous system (CNS) either through encapsulated material or attached to nanowires. Nanodrug delivery by any means is supposed to enhance neuroprotection due to rapid accumulation of drugs within the target area and a slow metabolism of the compound. These two factors enhance neuroprotection than the conventions drug delivery. However, this is still uncertain whether nanodrug delivery could alter the pharmacokinetics of compounds making it more effective or just longer exposure of the compound for extended period of time is primarily responsible for enhanced effects of the drugs. Our laboratory is engaged in understanding of the nanodrug delivery using TiO(2) nanowires in CNS injuries models, for example, spinal cord injury (SCI), hyperthermia and/or intoxication of nanoparticles with or without other comorbidity factors, that is, diabetes or hypertension in rat models. Our observations suggest that nanowired drug delivery is effective under normal situation of SCI and hyperthermia as evidenced by significant reduction in the blood-brain barrier (BBB) breakdown, brain edema formation, cognitive disturbances, neuronal damages, and brain pathologies. However, when the pathophysiology of these CNS injuries is aggravated by nanoparticles intoxication or comorbidity factors, adjustment in dosage of nanodrug delivery is needed. This indicates that further research in nanomedicine is needed to explore suitable strategies in achieving greater neuroprotection in CNS injury in combination with nanoparticles intoxication or other comorbidity factors for better clinical practices.

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Blood–Central Nervous System Barriers: The Gateway to Neurodegeneration, Neuroprotection and Neuroregeneration

Cited by 21 publications

References 260 publications

RETRACTED ARTICLE: Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron

RETRACTED ARTICLE: Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron

Neurovascular Unit in Chronic Pain

Nanowired drug delivery for neuroprotection in central nervous system injuries: modulation by environmental temperature, intoxication of nanoparticles, and comorbidity factors

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