Nose-to-brain co-delivery of repurposed simvastatin and BDNF synergistically attenuates LPS-induced neuroinflammation

Manickavasagam, Dharani; Li, Lin; Oyewumi, Moses O.

doi:10.1016/j.nano.2019.102107

Cited by 17 publications

(10 citation statements)

References 55 publications

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“…Open access epithelium pathway and bloodstream, making it suitable for neurological treatments. [26][27][28] We demonstrated that intranasal NBP treatment after brain injury improves neural regeneration. 26 NBP increased the endogenous neural progenitor cell (NPC) migration to the ischaemic striatum and other injured brain regions.…”

Section: Discussionmentioning

confidence: 84%

Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice

Zhao

et al. 2020

Stroke Vasc Neurol

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ObjectiveTo investigate the effects of DL-3-N-butylphthalide (NBP) via intranasal delivery after ischaemic stroke in mice.MethodsC57BL/6 mice were divided into three groups: sham, stroke with vehicle and stroke with NBP treatment. Ischaemic stroke was induced by permanent ligation of right middle cerebral artery with 7 min common carotid artery occlusion. NBP (100 mg/kg) or vehicle was intranasally administered at 1 hour after stroke and repeated once a day until sacrifice. Bromodeoxyuridine (BrdU) (50 mg/kg/day) was given from the third day until sacrifice. Sensorimotor function was tested during 1–21 days after stroke. Local cerebral blood flow in the ischaemic and peri-infarct regions was measured using laser Doppler flowmetry before, during and 3 days after ischaemia. Expressions of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase as well as regenerative marker BrdU in the peri-infarct region were analysed by western blotting and immunohistochemical methods.ResultsCompared with the vehicle group, NBP treatment significantly increased the VEGF expression in the poststroke brain. Stroke mice that received NBP showed significantly less vascular damage after stroke and more new neurons and blood vessels in the peri-infarct region at 21 days after stroke. In the adhesive removal test, the sensorimotor function of stroke mice treated with NBP performed significantly better at 1, 3 and 7 days after stroke compared with vehicle controls.ConclusionDaily intranasal NBP treatment provides protective and neurogenic/angiogenic effects in the poststroke brain, accompanied with functional improvements after a focal ischaemic stroke in mice.

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Section: Discussionmentioning

confidence: 84%

Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice

Zhao

et al. 2020

Stroke Vasc Neurol

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“…Based on the fact that the dimension of axons varies between 100 and 200 nm in different animal species [29,36,43,106], the majority of the nanocarriers disclosed for N-to-B delivery have been designed to have a size between 50 and 150 nm (Tables 3-5). However, as the trans-neuron transport is not the only N-to-B pathway, other nanocarriers with a mean size of 270 nm, or even 440 nm, have also shown some positive results in in vivo studies [107][108][109]. For example, using polysorbate-80 coated polystyrene NPs, it was observed that particle diameters of 100 nm showed more than a fourfold greater brain uptake than the same system with a 180 nm mean size.…”

Section: Influence Of Physicochemical Properties Of Nanocarriersmentioning

confidence: 99%

Using nanotechnology to deliver biomolecules from nose to brain — peptides, proteins, monoclonal antibodies and RNA

Borrajo

Alonso

2021

Drug Deliv. and Transl. Res.

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There is a growing number of biomolecules, including peptides, proteins, monoclonal antibodies and RNA, that could be potentially used for the treatment of central nervous system (CNS) diseases. However, the realization of their potential is being hampered by the extraordinary difficulties these complex biomolecules have to reach the brain in therapeutically meaningful amounts. Nose-to-brain (N-to-B) delivery is now being investigated as a potential option for the direct transport of biomolecules from the nasal cavity to different brain areas. Here, we discuss how different technological approaches enhance this N-to-B transport, with emphasis on those that have shown a potential for clinical translation. We also analyse how the physicochemical properties of nanocarriers and their modification with cell-penetrating peptides (CPPs) and targeting ligands affect their efficacy as N-to-B carriers for biomolecules. Graphical abstract

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“…Using a drug co-delivery system based on engineered PEG-PdLLA polymersomes to combine Sim, an anti-inflammatory agent, with BDNF, one study reported that intranasal administration markedly down-regulated the levels of many inflammatory cytokines in the frontal cortex, striatum and hippocampus (Manickavasagam, Lin, & Oyewumi, 2020). This homeostatic regulation was also reported against ischemic insults in rats subjected to temporary occlusion of the right middle cerebral artery with a decreased TNF production and an increased anti-inflammatory IL-10 production in microglia (Jiang et al, 2010;Jiang et al, 2011).…”

Section: Brain-derived Neurotrophic Factormentioning

confidence: 99%

“…Even though BDNF influence on microglia has not been directly studied in the context of HIV‐1 infection, it controls microglial over‐activation using the lipopolysaccharide (LPS) model of inflammation, helps preserve the brain architecture and counterbalances neurodegenerative progression (Lai et al, 2018). Using a drug co‐delivery system based on engineered PEG‐PdLLA polymersomes to combine Sim, an anti‐inflammatory agent, with BDNF, one study reported that intranasal administration markedly down‐regulated the levels of many inflammatory cytokines in the frontal cortex, striatum and hippocampus (Manickavasagam, Lin, & Oyewumi, 2020). This homeostatic regulation was also reported against ischemic insults in rats subjected to temporary occlusion of the right middle cerebral artery with a decreased TNF production and an increased anti‐inflammatory IL‐10 production in microglia (Jiang et al, 2010; Jiang et al, 2011).…”

Section: Neurotrophic Factors and Their Interactions With Hiv‐1mentioning

confidence: 99%

The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

Sénécal

Barat

Tremblay

2020

Glia

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Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of neurological impairments, termed HIV-associated neurocognitive disorder (HAND), following the infiltration of infected cells into the brain. Even though the implementation of antiretroviral therapy reduced the systemic viral load, the prevalence of HAND remains unchanged and infected patients develop persisting neurological disturbances affecting their quality of life. As a result, HAND have gained importance in basic and clinical researches, warranting the need of developing new adjunctive treatments. Nonetheless, a better understanding of the molecular and cellular mechanisms remains necessary. Several studies consolidated their efforts into elucidating the neurotoxic signaling leading to HAND including the deleterious actions of HIV-1 viral proteins and inflammatory mediators. However, the scope of these studies is not sufficient to address all the complexity related to HAND development. Fewer studies focused on an altered neuroprotective capacity of the brain to respond to HIV-1 infection. Neurotrophic factors are endogenous polyproteins involved in neuronal survival, synaptic plasticity, and neurogenesis. Any defects in the processing or production of these crucial factors might compose a risk factor rendering the brain more vulnerable to neuronal damages. Due to their essential roles, they have been investigated for their diverse interplays with HIV-1 infection. In this review, we present a complete description of the neurotrophic factors involved in HAND. We discuss emerging concepts for their therapeutic applications and summarize the complex mechanisms that down-regulate their production in favor of a neurotoxic environment. For certain factors, we finally address opposing roles that rather lead to increased inflammation.

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Nose-to-brain co-delivery of repurposed simvastatin and BDNF synergistically attenuates LPS-induced neuroinflammation

Cited by 17 publications

References 55 publications

Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice

Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice

Using nanotechnology to deliver biomolecules from nose to brain — peptides, proteins, monoclonal antibodies and RNA

The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

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