scholarly journals Extracellular vesicles from human adipose stem cells are neuroprotective after stroke in rats

2020 ◽  
Author(s):  
Francieli Rohden ◽  
Luciele Varaschini Teixeira ◽  
Luis Pedro Bernardi ◽  
Nicolly Paz Ferreira Marques ◽  
Mariana Colombo ◽  
...  

ABSTRACTIschemic stroke is a prominent cause of death and disability, demanding innovative therapeutic strategies. Accordingly, extracellular vesicles (EVs) released from mesenchymal stem cells are promising tools for stroke treatment. In this study, we evaluated the potential neuroprotective properties of EVs released from human adipose tissue stem cells (hAT-MSC), which were obtained from a healthy individual submitted to liposuction. A single intranasal EVs administration was performed 24 h after the ischemic stroke in rats. The EVs brain penetration and the tropism to brain zone of ischemia was observed 18 h after administration. Thus, we measured EVs neuroprotection against the ischemic stroke-induced impairment on long-term motor and behavioral performance. Indeed, one single intranasal EVs administration reversed the stroke damages on: i) front paws symmetry; ii) working memory, short- and long-term memory; iii) anxiety-like behavior. These findings highlight hAT-MSC-derived EVs as a promising therapeutic strategy in stroke.

2021 ◽  
Author(s):  
Francieli Rohden ◽  
Luciele Varaschini Teixeira ◽  
Luis Pedro Bernardi ◽  
Pâmela Cristina Lukasewicz Ferreira ◽  
Mariana Colombo ◽  
...  

Abstract Ischemic stroke is a prominent cause of death and disability, demanding for innovative and reachable therapeutic strategies. Thus, approaches presenting optimal period for therapeutic intervention and new routes of treatments administration as promising tools for stroke treatment. In this study, we evaluated the potential neuroprotective properties of nasally administration of human adipose tissue stem cells (hAT-MSC)-derived extracellular vesicles (EVs), obtained from healthy individuals submitted to liposuction. A single intranasal EVs (200 µg/Kg) administration performed 24 h after a focal permanent ischemic stroke in rats. Was observed a higher tropism of EVs by peri-infarct zone, surrounding the infarct core. Interestingly, in the same brain region, was observed a significant decrease in the volume of the infarct, improvement the blood-brain barrier and re-stabilization of vascularization. In addition, EVs recover the impairment on long-term motor and behavioral performance induced by ischemic stroke. Surprisingly, one single intranasal EVs administration reestablished: i) front paws symmetry; ii), short- and long-term memory; iii) anxiety-like behavior. In keeping with this, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy in stroke.


2021 ◽  
Author(s):  
Francieli Rohden ◽  
Luciele Varaschini Teixeira ◽  
Luis Pedro Bernardi ◽  
Pâmela Lukasewicz ◽  
Mariana Colombo ◽  
...  

Abstract Ischemic stroke is a major cause of death and disability, demanding innovative and accessible therapeutic strategies. Approaches presenting an optimal period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. We evaluated the potential neuroprotective properties of nasally administered human adipose tissue stem cells (hAT-MSCs)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. A single intranasal EV (200 µg/kg) was administered 24 h after a focal permanent ischemic stroke in rats. A higher tropism of EVs was observed in the peri-infarct zone surrounding the infarct core. In the same brain region, there was a significant decrease in the infarct volume, improvement of the blood-brain barrier, and re-stabilization of vascularization. In addition, EVs recovered the impairment of long-term motor and behavioral performance induced by an ischemic stroke. Surprisingly, one single intranasal EVs administration reestablished: i) front paws symmetry, ii) short- and long-term memory, and iii) anxiety-like behavior. In line with the findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke.


2021 ◽  
Vol 22 (23) ◽  
pp. 12860
Author(s):  
Francieli Rohden ◽  
Luciele Varaschini Teixeira ◽  
Luis Pedro Bernardi ◽  
Pamela Cristina Lukasewicz Ferreira ◽  
Mariana Colombo ◽  
...  

Ischemic stroke is a major cause of death and disability, intensely demanding innovative and accessible therapeutic strategies. Approaches presenting a prolonged period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. Here, we evaluated the potential neuroprotective properties of nasally administered human adipose tissue mesenchymal stem cell (hAT-MSC)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. After a single intranasal EV (200 µg/kg) administered 24 h after a focal permanent ischemic stroke in rats, a higher number of EVs, improvement of the blood–brain barrier, and re-stabilization of vascularization were observed in the recoverable peri-infarct zone, as well as a significant decrease in infarct volume. In addition, EV treatment recovered long-term motor (front paws symmetry) and behavioral impairment (short- and long-term memory and anxiety-like behavior) induced by ischemic stroke. In line with these findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.


Author(s):  
Ian Neath ◽  
Jean Saint-Aubin ◽  
Tamra J. Bireta ◽  
Andrew J. Gabel ◽  
Chelsea G. Hudson ◽  
...  

2010 ◽  
Vol 39 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Do-Hee Kim ◽  
Ok-Hyeon Kim ◽  
Joo-Hong Yeo ◽  
Kwang-Gill Lee ◽  
Geum-Duck Park ◽  
...  

1996 ◽  
Vol 351 (1346) ◽  
pp. 1455-1462 ◽  

The lateral frontal cortex is involved in various aspects of executive processing within short- and long-term memory. It is argued that the different parts of the lateral frontal cortex make distinct contributions to memory that differ in terms of the level of executive processing that is carried out in interaction with posterior cortical systems. According to this hypothesis, the mid-dorsolateral frontal cortex (areas 46 and 9) is a specialized system for the monitoring and manipulation of information within working memory, whereas the mid-ventrolateral frontal cortex (areas 47/12 and 45) is involved in the active retrieval of information from the posterior cortical association areas. Data are presented which support this two-level hypothesis that posits two distinct levels of interaction of the lateral frontal cortex with posterior cortical association areas. Functional activation studies with normal human subjects have demonstrated specific activity within the mid-dorsolateral region of the frontal cortex during the performance of tasks requiring monitoring of self-generated and externally generated sequences of responses. In the monkey, lesions restricted to this region of the frontal cortex yield a severe impairment in performance of the above tasks, this impairment appearing against a background of normal performance on several basic mnemonic tasks. By contrast, a more severe impairment follows damage to the mid-ventrolateral frontal region and functional activation studies have demonstrated specific changes in activity in this region in relation to the active retrieval of information from memory.


2021 ◽  
pp. 105477382110381
Author(s):  
Kelly Haskard-Zolnierek ◽  
Courtney Wilson ◽  
Julia Pruin ◽  
Rebecca Deason ◽  
Krista Howard

Individuals with hypothyroidism suffer from symptoms including impairments to cognition (i.e., “brain fog”). Medication can help reduce symptoms of hypothyroidism; however, brain fog may hinder adherence. The aim of this study was to determine if memory impairment and cognitive failures are related to treatment nonadherence in 441 individuals with hypothyroidism. Participants with a diagnosis of hypothyroidism and currently prescribed a thyroid hormone replacement medication were placed in two groups according to adherence level and compared on validated scales assessing impairments to memory and cognition. Results indicated a significant association between treatment nonadherence and self-reported brain fog, represented by greater cognitive and memory impairments. Nonadherent individuals indicated impairments with prospective, retrospective, and short- and long-term memory; and more cognitive failures, compared to adherent individuals. Findings suggest the importance of interventions to enhance adherence for individuals with brain fog, such as encouraging the use of reminders.


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