Advancement in Brain Vasculature Manipulations: Harnessing Nano-Lipolysis for
Precision Treatment of Lacunar Ischemic Stroke
Authors: Laurence Copeland, Kevin Zheng, Sadat Uddin, Lesley Gutierrez, Megan De Jesus
Georgia Institute of Technology
BMED 4803: Intro to Neuroengineering
Dr. Annabelle Singer
December 11, 2023
Abstract
Lacunar ischemic strokes pose a significant challenge in neurology, necessitating novel interventions to
improve therapeutic outcomes. Despite extensive research in stroke treatment, there is a conspicuous
absence of a general method for precisely determining the optimal intervention point for lacunar strokes.
Existing literature highlights various techniques assessing different aspects of stroke pathology, yet none
efficiently addresses the specific requirements of lacunar ischemic strokes without compromising
treatment efficacy. This paper introduces a groundbreaking approach, utilizing nanoparticle-induced
lipolysis via cholesterol-degrading enzymes, referred to as nano-lipolysis, offering a direct measurement
of lipid metabolism as a superior metric for evaluating the readiness of lacunar strokes for intervention.
Through a comprehensive research strategy involving in vitro experimentation, animal models, and
clinical studies, we demonstrate the effectiveness of nano-lipolysis over existing techniques. Our
experiments cover the spectrum of lacunar stroke subtypes, showcasing the accelerated efficacy and
precision of nano-lipolysis in producing optimal conditions for intervention. Anticipated implications of
our research include significant advancements in the spatial and temporal scale of treating lacunar
ischemic strokes, paving the way for widespread, effective implementation without compromising
therapeutic quality. This innovative approach holds the potential to redefine the landscape of lacunar
stroke interventions and improve patient outcomes.
Figures
Figure 1. Lacunar Infarct Physiology.
(A) Overview of the vasculature present in a coronal
slice of the human brain. Lacunar infarcts can be
present in blood vessels small, ~10 micrometers, and
deep within the brain and affect nerves surrounding
the blood vessels, causing long-lasting damage
(Mustapha et al., 2019). This small size poses a new
risk not present in vessels on the surface of the brain.
(B) Normal blood vessels show blood flow (top) and
blood vessels containing plaque from high levels of
cholesterol leading to a narrowed pathway and
decreased blood flow (bottom). This decrease in
blood flow leads to lacunar infarcts developing and
an eventual lacunar ischemic stroke. Figure was
created with BioRender.com.
Figure 2. General Lipid Breakdown Mechanism.
Lipase circulating in the blood will target
triglycerides that are stored in adipose cells.
Triglycerides are broken down by lipoprotein lipases
into glycerols and free fatty acids (Langin 2006).
These will enter the bloodstream to be used as an
energy source for other cells. Figure was created with
BioRender.com.
Figure 3. Schematic Diagram of Lipolysis Drug Treatment for Lacunar Ischemic Stroke
(A) Patient presenting with early symptoms suggestive of lacunar ischemic stroke. (B) Evaluation and diagnosis of
lacunar stroke at hospital based on clinical examination and imaging. (C) Decision to proceed with lipolysis drug
treatment and administration of intravenous lipolysis enzyme injection. (D) Lipolysis enzymes circulate systemically
in the vasculature and accumulate at lipid deposits associated with the clot. (E) Enzymatic breakdown of lipid
deposits. (F) Restoration of blood flow due to dismantling and clearance of clot. (G) Post-treatment monitoring and
recovery. Figure was created with BioRender.com
Figure 4. Lipolysis Drug Treatment: Enzyme Breakdown of Plaque in Blood Vessel (A) Enzymes are injected
into the bloodstream, binding to plaque in the vessel. Enzymes are synthetically made to have special binding sites
in which they bind to plaque particularly (B) Once the enzymes bind to the plaque it begins to break it down into its
corresponding free fatty acids. The free fatty acids become a new source of energy in the body and blood flow
returns to normal. Figure was created with BioRender.com
Figure 5. In-vivo Mouse Model. (A) C57 mice undergo surgery to introduce adipose tissue into brain blood vessels
inducing a stroke. (B) Mice blood flow is analyzed by measuring blood pressure and visualized using imaging
techniques. (C Lipolysis enzymes injected into the bloodstream of mice. (D) Mice blood flow analyzed for recovery.
(E) Human trials done after successful mouse trials. Figure was created with BioRender.com.
A
B
Figure 6. Post-lipolysis Validation. (A). As the enzyme reaches the plaque site and starts lipolysis, the diameter of
the vessel starts to return to its original diameter. (B). The blood pressure changes during stroke onset and after the
lipolysis intervention. After lipolysis treatment, the blood pressure will eventually drop to the mean arterial pressure
(Thakkar et al., 2019). Figure was created with BioRender.com
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