Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson's disease mouse model

Can your doctor and stroke hospital rub two neurons together and deduce that this could be an effective way to deliver BDNF?  BDNF is very useful in our recovery. Does your doctor know that and is doing ANYTHING AT ALL about it? Or intranasal delivery?

Yes, this is in mice and for Parkinsons but do they have the ability to think outside the failed box of stroke recovery? Ask, and not politely, how they are going to get you 100% recovered. Anything less is complete failure on their part and the board of directors should have a policy to replace those failures. I take no prisoners in trying to get stroke solved.

• BDNF (137 posts to April 2011)

• nasal delivery (10 posts to December 2017)

• 13 nasal delivery options (6 posts to April 2014)

 

Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson's disease mouse model

Ji R¹, Smith M¹, Niimi Y¹, Karakatsani ME¹, Murillo MF¹, Jackson-Lewis V^2,3,4, Przedborski S^2,5,3,4, Konofagou EE^6,7.

Author information

1

Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2

Department of Pathology & Cell Biology, Columbia University, New York, New York, USA.

3

Department of the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, USA.

4

Department of the Columbia Translational Neuroscience Initiative, Columbia University, New York, New York, USA.

5

Department of Neurology, Columbia University, New York, New York, USA.

6

Department of Biomedical Engineering, Columbia University, New York, New York, USA. ek2191@columbia.edu.

7

Department of Radiology, Columbia University, New York, New York, USA. ek2191@columbia.edu.

Abstract

Focused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson's disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had significantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any differences. Additionally, behavioral changes were only observed in the IN + FUS treated mice, indicating improved motor control function in the treated hemisphere. These findings demonstrate the robustness of the method and potential of IN + FUS for the delivery of bioactive factors for treatment of neurodegenerative disorder.

PMID:

31852909

PMCID:

PMC6920380

DOI:

10.1038/s41598-019-55294-5

Free PMC Article

Nanoparticle nasal spray may offer rapid and safe delivery of drugs to the brain

This has 13 other nasal options, which ones is your hospital testing?

Using nanoparticles, not needles, to deliver drugs into the eye  - 13 options

The latest here:

Nanoparticle nasal spray may offer rapid and safe delivery of drugs to the brain 

Traversing the blood-brain barrier is a challenge for drug developers. Now, after testing the method in locusts, a team of engineers shows how an aerosol nasal spray containing gold nanoparticles may offer a non-invasive and rapid way to deliver drugs to the brain.

Researchers suggest that delivering drugs to the brain using nanoparticles in a nasal spray could be an effective and rapid method capable of overcoming the problem of traversing the blood-brain barrier.

The team - from the University of Washington in St. Louis (WUSTL), MO - describes the proof-of-concept research in the journal Scientific Reports.
For the brain to function, it must operate in a tightly controlled chemical environment that is protected from the more varied fluctuations of the rest of the body.
This stable environment is maintained by the blood-brain barrier, which comprises layers of specialized cells in the inner linings of the small blood vessels in the brain and spinal cord.
The blood-brain barrier prevents toxins from entering the tissues of the brain and spinal cord. Unfortunately, it does the job so well that it also keeps out many drugs, such as those used to kill cancer cells.

One way to overcome this is to deliver drugs to the brain using injections. However, such invasive approaches are risky in that they can damage tissue and have little control over the distribution of the drugs from the point of injection, note the study researchers.

Thus, in a bid to find an effective and less risky alternative, the WUSTL team decided to explore the potential of using nanoparticles to carry drugs to the brain through the nose.

Nose offers easy access to the brain

Interest in using nanotechnology - the ability to control matter at the atomic and molecular scale - to develop new diagnostic tools and treatments is growing, note the authors in their study report.
A number of new nanomaterials have been used to carry drugs to specific targets in organs and tissues. These appear to maximize drug effectiveness while minimizing side effects.
Co-author Barani Raman, associate professor of biomedical engineering, says that the nose offers the shortest - and most likely the easiest - route to the brain.
He and his colleagues note that from various studies, gold nanoparticles have emerged as the material of choice for drug delivery. They are relatively easy to synthesize and customize, and they have good biocompatibility.
The team developed a new aerosol diffusion method that deposits gold nanoparticles in the upper regions of the nasal cavity. They produced the nanoparticles to a controlled shape, size, and surface charge, and tagged them with fluorescent markers so that they could track them.

Locusts offer a good model of the human blood-brain barrier

The researchers tested the effectiveness of the nanoparticle aerosol in locusts because their blood-brain barriers bear similarities to those of humans - especially when going through the nasal route.

Prof. Raman explains that in humans, to reach the brain through the nose, the nanoparticles have to travel through the olfactory bulb and then the olfactory cortex, "two relays and you've reached the cortex," he says.

"The same is true for invertebrate olfactory circuitry," he adds, "although the latter is a relatively simpler system, with [a] supraesophageal ganglion instead of an olfactory bulb and cortex."
The team exposed the locusts' antennae to the aerosol and tracked the progress of the tagged nanoparticles. Within a few minutes, the nanoparticles had traversed the insects' olfactory circuitry, passed through the brain-blood barrier, and suffused the brain tissue.
The team showed that the nanoparticles did not affect the insects' brain function. They measured the electrophysiological responses of the locusts' olfactory neurons before and after treatment and found no discernible difference up to several hours afterwards.
The researchers say that the next stage of their research will be to load the nanoparticles with different drugs and use ultrasound to target precise doses to reach specific areas of the brain. Such methods could potentially make a big difference to the treatment of brain tumors.

 

Novel Alzheimer's treatment uses microscopic droplets of fat to carry drugs into the brain

If we ever get a drug developed that would help stroke recovery this could be used to deliver it to the brain. As long as we have someone keeping track of a stroke strategy and all the moving parts that need to be remembered.  Or maybe these 13 nasal delevery options? I bet no one in stroke is keeping track of this. 

Novel Alzheimer's treatment uses microscopic droplets of fat to carry drugs into the brain

New Alzheimer's treatment could be delivered as nasal spray
Researchers have developed a novel treatment that could block the development of Alzheimer's disease using microscopic droplets of fat to carry drugs into the brain. This treatment approach, which is used to target drugs to cancer cells, has been successfully applied to Alzheimer's disease for the first time, restoring memory loss in mice.
The study, which was led by researchers at Lancaster University and funded by Alzheimer's Society, is published  in the journal Nanomedicine: Nanotechnology, Biology and Medicine.
The treatment uses tiny droplets of fat, called nanoliposomes, which are coated in protein fragments that are able to stop amyloid protein accumulating into plaques, even at low concentrations. Amyloid plaques are the toxic clumps of protein that cause damage to cells in the brains of people with Alzheimer's disease.
Mice that were genetically altered to develop Alzheimer's disease were injected with the nanoliposomes for three weeks. Those which received the drug recovered their long-term memory and could recognise familiar objects after a 24-hour period. In comparison, mice which received a placebo injection had no memory of objects seen the day before.
Lead researcher, Professor David Allsop, commented: "Following results this summer, there is renewed optimism for antibody drugs - treatments that harness the body's immune system to target amyloid plaques. However if these prove successful, treatments will have to be administered in a clinic by an IV drip and could have some potentially harmful side effects.
"Using nanoliposomes offers an alternative way to inhibit the toxic build-up of amyloid plaques without activating an immune response in the brain. Our hope is that this could one day be administered by something as simple and non-invasive as a nasal spray, which patients could use in the comfort of their own home."

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Nanoliposomes are already used to better target toxic chemotherapy drugs to cancer cells. Recent studies have also shown that the fat droplets can pass directly into the brain through the nose, opening up the possibility of using a nasal spray to administer treatments for brain diseases, such as Alzheimer's.
Commenting on the need for innovative approaches to dementia treatments, Dr Doug Brown, Director of Research and Development at Alzheimer's Society, said: "With no new dementia drugs in nearly 15 years, we're at a critical time for dementia research. It's absolutely vital we continue to sniff-out new approaches to getting drugs into the brain. While we wait in anticipation for the results of ongoing clinical trials, Alzheimer's Society will continue to fund innovative research to tackle dementia head-on."
"Nanotechnology is promising great benefits to people with many different types of cancer, and it's exciting that it could one day offer the same hope to people with the most common form of dementia." 
There are 850,000 people in the UK living with dementia, and currently available drugs are only able to treat the symptoms of dementia, rather than slowing its progression. The research team at Lancaster University are now seeking investment from industry to take their novel treatment forward to be tested in people.

Source:

Lancaster University

Researchers Ride New Sound Wave to Health Discovery

This would seem to be incredibly useful for those drugs delivered to the brain through the nasal cavity. But don't worry, This will never be followed up since we have NO stroke leadership. 

Researchers Ride New Sound Wave to Health Discovery 

Acoustics experts have created a new class of sound wave - the first in more than half a century - in a breakthrough they hope could lead to a revolution in stem cell therapy.
The team at RMIT University in Melbourne, Australia, combined two different types of acoustic sound waves called bulk waves and surface waves to create a new hybrid: "surface reflected bulk waves".
The first new class of sound wave discovered in decades, the powerful waves are gentle enough to use in biomedical devices to manipulate highly fragile stem cells without causing damage or affecting their integrity, opening new possibilities in stem cell treatment.
Dr Amgad Rezk, from RMIT's Micro/Nano Research Laboratory, said the team was already using the discovery to dramatically improve the efficiency of an innovative new "nebuliser" that could deliver vaccines and other drugs directly to the lung.
"We have used the new sound waves to slash the time required for inhaling vaccines through the nebuliser device, from 30 minutes to as little as 30 seconds," Rezk said.
"But our work also opens up the possibility of using stem cells more efficiently for treating lung disease, enabling us to nebulise stem cells straight into a specific site within the lung to repair damaged tissue.
"This is a real game changer for stem cell treatment in the lungs."
The researchers are using the "surface reflected bulk waves" in a breakthrough device, dubbed HYDRA, which converts electricity passing through a piezoelectric chip into mechanical vibration, or sound waves, which in turn break liquid into a spray.
"It's basically 'yelling' at the liquid so it vibrates, breaking it down into vapour," Rezk said.
Bulk sound waves operate similar to a carpet being held at one end and shaken, resulting in the whole substrate vibrating as one entity. Surface sound waves on the other hand operate more like ocean waves rolling above a swimmer's head.
"The combination of surface and bulk wave means they work in harmony and produce a much more powerful wave," said Rezk, who co-authored the study with Ph.D. researcher James Tan.
"As a result, instead of administering or nebulising medicine at around 0.2ml per minute, we did up to 5ml per minute. That's a huge difference."
The breakthrough HYDRA device is improving the effectiveness of a revolutionary new type of nebuliser developed at RMIT called Respite. Cheap, lightweight and portable, the advanced Respite nebuliser can deliver everything from precise drug doses to patients with asthma and cystic fibrosis, to insulin for diabetes patients, and needle-free vaccinations to infants.
The HYDRA research will be published on Thursday 7 January in the scientific journal Advanced Materials.
Source: RMIT University

Nose-to-Brain Drug Delivery by Nanoparticles in the Treatment of Neurological Disorders

Ask your competent? doctor which drug therapies are close enough to needing this drug delivery system to stop the neuronal cascade of death.  I bet s/he has no clue what this is about, thus letting your neurons die due to inaction. Good luck with that.
I've written about 13 other nasal delivery options here.
Nose-to-Brain Drug Delivery by Nanoparticles in the Treatment of Neurological Disorders

Ong WY¹, Maran SS, Costantino L.

Author information

Abstract

Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. With this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solutions formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease, and infectious diseases. The delivery of drugs to the brain via nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles (Np) and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain area and variability in the adsorbed dose still represent research topics that need to be considered with a view of clinical translation of these delivery systems.

Using nanoparticles, not needles, to deliver drugs into the eye

Getting through the mucous on the eye this way would seem to be similar to trying to deliver drugs through the nasal cavity to the brain. Your doctor and researcher (If any good at all) will immediately recognize the potential. Or not, since we don't seem to have anyone with brains that publicly writes about this stuff.  Does your doctor know about any of these 12 or the newest one?
1.  Brain Targetting through Intranasal Route
 
2.  New Therapy for MS on Horizon?
 
3.  Nasal Administration of Recombinant Osteopontin Attenuates Early Brain Injury After Subarachnoid Hemorrhage
 
4.  Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia–ischemia in neonatal rats
5.  Toward the First Nose Drops to Treat Brain Cancer
6.  Intranasal drug delivery disruptor OptiNose signs licensing deal for migraine treatment
7.  Intranasal VEGF - A and VEGF - E in a modified Levine model of stroke
8.  UW Spinoff Impel Neuropharma Passes Key Nose-to-Brain Clinical Trial 
9.  Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study
10.  aFGF delivered intranasally induces neurogenesis
11.  TGF alpha and stroke rehab
12.  A Nasal Spray against Alzheimer's Disease and Stroke
 
The newest one here: 

Using nanoparticles, not needles, to deliver drugs into the eye