Intranasal delivery of phenytoin-loaded nanoparticles to the brain suppresses pentylenetetrazol-induced generalized tonic clonic seizures in epilepsy mouse model

2021 ◽  
Author(s):  
Amal Yousfan ◽  
Noelia Rubio Carrero ◽  
Mohamad Al-Ali ◽  
Abdul Hakim Nattouf ◽  
Houmam Kafa
Keyword(s):  
Mouse Model ◽  
Mouse Brain ◽  
Chitosan Nanoparticles ◽  
Intranasal Delivery ◽  
Anti Epileptic Drug ◽  
Clonic Seizures ◽  
The Brain

In this work we describe the preparation and characterization of lecithin-chitosan nanoparticles (L10Ci+), and investigate their ability to deliver the anti-epileptic drug phenytoin (PHT) to mouse brain following intranasal (IN)...

scholarly journals Intranasal Delivery of Collagen-Loaded Neprilysin Clears Beta-Amyloid Plaques in a Transgenic Alzheimer Mouse Model

2021 ◽  
Vol 13 ◽  
Author(s):  
Christian Humpel
Keyword(s):  
Mouse Model ◽  
Mouse Brain ◽  
Brain Slices ◽  
Beta Amyloid ◽  
Intranasal Delivery ◽  
Degrading Enzyme ◽  
Amyloid Aβ ◽  
Potent Drug ◽  
The Brain ◽  
Ad Mouse Model

Alzheimer’s disease (AD) is pathologically characterized by extracellular beta-amyloid (Aβ) plaques and intraneuronal tau tangles in the brain. A therapeutic strategy aims to prevent or clear these Aβ plaques and the Aβ-degrading enzyme neprilysin is a potent drug to degrade plaques. The major challenge is to deliver bioactive neprilysin into the brain via the blood-brain barrier. The aim of the present study is to explore if intranasal delivery of neprilysin can eliminate plaques in a transgenic AD mouse model (APP_SweDI). We will test if collagen or platelets are useful vehicles to deliver neprilysin into the brain. Using organotypic brain slices from adult transgenic APP_SweDI mice, we show that neprilysin alone or loaded in collagen hydrogels or in platelets cleared cortical plaques. Intransasal delivery of neprilysin alone increased small Aβ depositions in the middle and caudal cortex in transgenic mice. Platelets loaded with neprilysin cleared plaques in the frontal cortex after intranasal application. Intranasal delivery of collagen-loaded neprilysin was very potent to clear plaques especially in the middle and caudal parts of the cortex. Our data support that the Aβ degrading enzyme neprilysin delivered to the mouse brain can clear Aβ plaques and intranasal delivery (especially with collagen as a vehicle) is a fast and easy application. However, it must be considered that intranasal neprilysin may also activate more plaque production in the transgenic mouse brain as a side effect.

scholarly journals Evaluation of Neuroprotective Effect of Thymoquinone Nanoformulation in the Rodent Cerebral Ischemia-Reperfusion Model

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Yu Xiao ◽  
Ying-Xian Zhu ◽  
Ju-Yuan Bu ◽  
Guo-Wei Li ◽  
Jian-Hui Zhou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Ischemia Reperfusion ◽  
Chitosan Nanoparticles ◽  
Intranasal Delivery ◽  
Cerebral Ischemia Reperfusion ◽  
Biochemical Studies ◽  
Neuroprotective Efficacy ◽  
The Brain

The purpose of the present study was to evaluate the neuroprotective efficacy of optimized thymoquinone loaded PLGA-chitosan nanoparticles delivered via nose to brain route in the rodent cerebral ischemia-reperfusion model. The neuroprotective efficacy of the optimized thymoquinone loaded PLGA-chitosan nanoparticles was evaluated in middle cerebral artery occluded rats by various pharmacodynamic and biochemical studies. The pharmacokinetics of thymoquinone loaded PLGA-chitosan nanoparticles in the brain and blood plasma together with qualitative localization of florescent labelled PLGA-chitosan nanoparticles in brain tissues were also determined. Intranasal delivery of optimized thymoquinone loaded PLGA-chitosan nanoparticles (183.5±8.2 nm,33.63±2.25 mV) to brain significantly reduced the ischemia infarct volume and enhanced the locomotor activity and grip strength in the middle cerebral artery occluded rats. Biochemical studies showed that intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles significantly reduced the lipid peroxidation but elevated the glutathione, catalase, and superoxide dismutase in the brain of middle cerebral artery occluded rats. The pharmacokinetic and localization studies showed that thymoquinone loaded PLGA-chitosan nanoparticles facilitated the delivery of thymoquinone to brain by intranasal nose to brain transport pathways and enhanced their pharmacokinetic profile in brain tissues. Thus, intranasal delivery of thymoquinone loaded PLGA-chitosan nanoparticles to brain could be potentially used for the neuroprotection and treatment of cerebral ischemia.

scholarly journals Data on enrichment of chitosan nanoparticles for intranasal delivery of oligonucleotides to the brain

Data in Brief ◽  
2020 ◽  
Vol 28 ◽  
pp. 105093
Author(s):  
Vasyl Sava ◽  
Oksana Fihurka ◽  
Anastasia Khvorova ◽  
Juan Sanchez-Ramos
Keyword(s):  
Chitosan Nanoparticles ◽  
Intranasal Delivery ◽  
The Brain

Longitudinal Characterization of the Brain Proteomes for the Tg2576 Amyloid Mouse Model Using Shotgun Based Mass Spectrometry

2012 ◽  
Vol 11 (12) ◽  
pp. 6159-6174 ◽  
Author(s):  
Ganna Shevchenko ◽  
Magnus Wetterhall ◽  
Jonas Bergquist ◽  
Kina Höglund ◽  
Lars I. Andersson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Model ◽  
The Brain

scholarly journals Azole Heteroresistance in Cryptococcus neoformans: Emergence of Resistant Clones with Chromosomal Disomy in the Mouse Brain during Fluconazole Treatment

2013 ◽  
Vol 57 (10) ◽  
pp. 5127-5130 ◽  
Author(s):  
Edward Sionov ◽  
Yun C. Chang ◽  
Kyung J. Kwon-Chung
Keyword(s):  
Mouse Model ◽  
Cryptococcus Neoformans ◽  
Mouse Brain ◽  
Content Type ◽  
The Brain ◽  
Strain Dependent ◽  
Is Strain

ABSTRACTWe have previously reported thatCryptococcus neoformansstrains are innately heteroresistant to fluconazolein vitro, producing minor, highly resistant subpopulations due to adaptive formation of disomic chromosomes. Using a mouse model, we assessed the emergence of heteroresistant clones in the brain during fluconazole treatment and found that the occurrence of heteroresistant clonesin vivowith chromosomal disomy is strain dependent. Interestingly, emergence of heteroresistant clonesin vivowas unrelated to the strain's MIC to fluconazole.

scholarly journals Genetic Disruption of WASHC4 Drives Endo-lysosomal Dysfunction and Cognitive-Movement Impairments in Mice and Humans

2020 ◽  
Author(s):  
Jamie L. Courtland ◽  
Tyler W. A. Bradshaw ◽  
Greg Waitt ◽  
Erik J. Soderblom ◽  
Tricia Ho ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Retrospective Analysis ◽  
Mouse Brain ◽  
Motor Deficits ◽  
Motor Impairments ◽  
Proteomics Analysis ◽  
Lysosomal Dysfunction ◽  
The Brain ◽  
Progressive Motor Deficits

ABSTRACTMutation of the WASH complex subunit, SWIP, is implicated in human intellectual disability, but the cellular etiology of this association is unknown. We identify the neuronal WASH complex proteome, revealing a network of endosomal proteins. To uncover how dysfunction of endosomal SWIP leads to disease, we generate a mouse model of the human WASHC4c.3056C>G mutation. Quantitative spatial proteomics analysis of SWIPP1019R mouse brain reveals that this mutation destabilizes the WASH complex and uncovers significant perturbations in both endosomal and lysosomal pathways. Cellular and histological analyses confirm that SWIPP1019R results in endo-lysosomal disruption and uncover indicators of neurodegeneration. We find that SWIPP1019R not only impacts cognition, but also causes significant progressive motor deficits in mice. Remarkably, a retrospective analysis of SWIPP1019R patients confirms motor deficits in humans. Combined, these findings support the model that WASH complex destabilization, resulting from SWIPP1019R, drives cognitive and motor impairments via endo-lysosomal dysfunction in the brain.

scholarly journals In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for cerebral malaria.

1995 ◽  
Vol 182 (3) ◽  
pp. 643-653 ◽  
Author(s):  
K Willimann ◽  
H Matile ◽  
N A Weiss ◽  
B A Imhof
Keyword(s):  
Plasmodium Falciparum ◽  
Mouse Model ◽  
Cerebral Malaria ◽  
Mouse Brain ◽  
Scid Mouse ◽  
Severe Combined Immunodeficiency ◽  
Human Erythrocytes ◽  
Combined Immunodeficiency ◽  
The Brain

Cerebral malaria is a fatal complication of infection by Plasmodium falciparum in man. The neurological symptoms that characterize this form of malarial disease are accompanied by the adhesion of infected erythrocytes to the vasculature of the brain. To study this phenomenon in vivo, an acute phase severe combined immunodeficiency (SCID) mouse model was developed in which sequestration of P. falciparum-infected human erythrocytes took place. During acute cerebral malaria in humans, the expression of intercellular adhesion molecule-1 (ICAM-1) is induced in vascular endothelium by inflammatory reactions. Acute phase ICAM-1 expression can also be obtained in SCID mice. The endothelium of the midbrain region was the most responsive to such inflammatory stimulus. It is noteworthy that the reticular formation in the midbrain controls the level of consciousness, and loss of consciousness is a symptom of cerebral malaria. We found that infected human erythrocytes were retained 24 times more than normal erythrocytes in ICAM-1-positive mouse brain. Sequestration to the brain was reduced by anti-ICAM-1 antibodies. These in vivo results were confirmed by the binding of P. falciparum-infected erythrocytes to the ICAM-1-positive endothelium in tissue sections of mouse brain. We conclude that the SCID mouse serves as a versatile in vivo model that allows the study of P. falciparum-infected erythrocyte adhesion as it occurs in human cerebral malaria. Upregulation of ICAM-1 expression in the region of the midbrain correlates with increased retention of malaria-infected erythrocytes and with the symptoms of cerebral malaria.

scholarly journals Mouse model of the human serotonin transporter-linked polymorphic region

2019 ◽  
Author(s):  
Lukasz Piszczek ◽  
Simone Memoli ◽  
Angelo Raggioli ◽  
José Viosca ◽  
Jeanette Rientjes ◽  
...  
Keyword(s):  
Mouse Model ◽  
Emotional Disorders ◽  
Serotonin Transporter ◽  
Single Copy ◽  
Weight Of Evidence ◽  
Polymorphic Region ◽  
Common Genetic Variants ◽  
The Impact ◽  
The Brain

AbstractGenetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioural traits we set out to develop a mouse model of the human 5-HTT- LPR. Here we describe the creation and characterization of a set of mouse lines with single copy human transgenes carrying the short and long 5-HTT-LPR variants.

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