scholarly journals Modulated focused ultrasound for treatment of de-myelinating axons in multiple sclerosis lesions – pilot animal studies

2018 ◽  
Author(s):  
Pierre D. Mourad

Multiple sclerosis is a debilitating disease whose symptoms arise from de-myelination of axons within brain tissue with an attendant loss of central and peripheral function. We among others have shown that transcranial delivery of pulsed focused ultrasound (pFU) can non-destructively activate central neural circuits. Others have shown enhanced myelin remodeling of axons activated by laser light in an optogenetic mouse model. We hypothesize that pFU activation of axons within MS lesions in a rodent model will decrease their de-myelination and increase their re-myelination. If successful, this non-invasive therapy may lead to rapid advancements in the treatment of MS and other de-myelinating neurological disorders.

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
T. A. Olmstead ◽  
P. A. Chiarelli ◽  
D. J. Griggs ◽  
A. M. McClintic ◽  
A. N. Myroniv ◽  
...  

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 120 ◽  
Author(s):  
Bakhtiar Bukari ◽  
Rasika M. Samarasinghe ◽  
Jinjutha Noibanchong ◽  
Sarah L. Shigdar

The blood-brain barrier (BBB) is a highly specialised network of blood vessels that effectively separates the brain environment from the circulatory system. While there are benefits, in terms of keeping pathogens from entering the brain, the BBB also complicates treatments of brain pathologies by preventing efficient delivery of macromolecular drugs to diseased brain tissue. Although current non-invasive strategies of therapeutics delivery into the brain, such as focused ultrasound and nanoparticle-mediated delivery have shown various levels of successes, they still come with risks and limitations. This review discusses the current approaches of therapeutic delivery into the brain, with a specific focus on non-invasive methods. It also discusses the potential for aptamers as alternative delivery systems and several reported aptamers with promising preliminary results.


2013 ◽  
Vol 134 (5) ◽  
pp. 4181-4181
Author(s):  
Sandra L. Poliachik ◽  
Tatiana D. Khokhlova ◽  
Yak-Nam Wang ◽  
Julianna C. Simon ◽  
Ted S. Gross ◽  
...  

2011 ◽  
Vol 17 (6) ◽  
pp. 647-657 ◽  
Author(s):  
David Baker ◽  
Wouter Gerritsen ◽  
Jon Rundle ◽  
Sandra Amor

Experimental autoimmune encephalomyelitis (EAE) is a spectrum of neurological disorders in laboratory animals that is used to model multiple sclerosis (MS). However, few agents have translated from efficacy in EAE to the treatment of human disease. Although this may reflect species differences in pathological disease mechanisms, importantly it may also relate to the practice of how drugs and models are currently used. This often bears very little resemblance to the clinical scenarios where treatments are investigated, such that lack of appreciation of the biology of disease may doom drugs to failure. The use of EAE is critically appraised with the aim of provoking thought, improving laboratory practise and aiding researchers and reviewers to address quality issues when undertaking, reporting and interpreting animal studies related to MS research. This is important as many researchers using EAE could and should do more to improve the quality of the studies.


2014 ◽  
Vol 40 (9) ◽  
pp. 2113-2124 ◽  
Author(s):  
Sandra L. Poliachik ◽  
Tatiana D. Khokhlova ◽  
Yak-Nam Wang ◽  
Julianna C. Simon ◽  
Michael R. Bailey

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 786
Author(s):  
Valerie L. Jewells ◽  
Hong Yuan ◽  
Joseph R. Merrill ◽  
Jonathan E. Frank ◽  
Akhil Patel ◽  
...  

The study aims to assess site assessment of the performance of 18F-PBR-111 as a neuroinflammation marker in the cuprizone mouse model of multiple sclerosis (MS). 18F-PBR-111 PET imaging has not been well evaluated in multiple sclerosis applications both in preclinical and clinical research. This study will help establish the potential utility of 18F-PBR-111 PET in preclinical MS research and future animal and future human applications.18F-PBR-111 PET/CT was conducted at 3.5 weeks (n = 7) and 5.0 weeks (n = 7) after cuprizone treatment or sham control (n = 3) in the mouse model. A subgroup of mice underwent autoradiography with cryosectioned brain tissue. T2 weighted MRI was performed to obtain the brain structural data of each mouse. 18F-PBR-111 uptake was assessed in multiple brain regions with PET and autoradiography images. The correlation between autoradiography and immunofluorescence staining of neuroinflammation (F4/80 and CD11b) was measured. Compared to control mice, significant 18F-PBR-111 uptake in the corpus callosum (p < 0.001), striatum (caudate and internal capsule, p < 0.001), and hippocampus (p < 0.05) was identified with PET images at both 3.5 weeks and 5.0 weeks, and validated with autoradiography. No significant uptake differences were detected between 3.5 weeks and 5.0 weeks assessing these regions as a whole, although there was a trend of increased uptake at 5.0 weeks compared to 3.5 weeks in the CC. High 18F-PBR-111 uptake regions correlated with microglial/ macrophage locations by immunofluorescence staining with F4/80 and CD11b antibodies. 18F-PBR-111 uptake in anatomic locations correlated with activated microglia at histology in the cuprizone mouse model of MS suggests that 18F-PBR-111 has potential for in vivo evaluation of therapy response and potential for use in MS patients and animal studies.


2009 ◽  
Vol 15 (7) ◽  
pp. 795-801 ◽  
Author(s):  
S Al-Izki ◽  
G Pryce ◽  
G Giovannoni ◽  
D Baker

Background In multiple sclerosis (MS), demyelinating and neurodegenerative lesions develop throughout the central nervous system, which result in a loss of neurotransmission. As a result, people with MS exhibit a wide range of symptoms including dysfunction of the bladder, which can lead to urinary incontinence or retention. Such signs can develop in animal models of MS. Current assessments of bladder properties in animal models are generally invasive, electrophysiological techniques. Objective The use of a non-invasive, ultrasound system for measuring bladder volume in a mouse model of MS. Methods Chronic relapsing experimental autoimmune encephalomyelitis was induced in mice. The bladder volume was assessed using ultrasonography, during the disease course and following therapy with bethanechol chloride. Results It was demonstrated that volumes obtained ultrasonically positively-correlated (r = 0.960) with the urine volumes obtained by manual expression. It was also shown for the first time that bladder size increased significantly in mice with residual neurological deficit. Indeed, this increase in bladder size showed a strong, positive-correlation (r = 0.951) with the hind limb spasticity. Following treatment with bethanechol chloride, bladder volume significantly decreased in mice with chronic experimental autoimmune encephalomyelitis. Conclusion This study demonstrates a novel outcome measure in experimental MS that allows; repeated, non-invasive, high resolution ultrasonic monitoring of bladder function.


PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24730 ◽  
Author(s):  
Scott R. Burks ◽  
Ali Ziadloo ◽  
Hilary A. Hancock ◽  
Aneeka Chaudhry ◽  
Dana D. Dean ◽  
...  

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