Sunday, November 24, 2024 11/24/2024

Repurposing Metformin to Offset Stroke Risk and Injury in Comorbid Populations of Smokers

Award Number: R01NS117906
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Abstract: Recently published in vitro and in vivo findings strongly suggest that blood-brain barrier (BBB) impairment and increased risk for stroke by tobacco smoke (TS) develop largely in response to common key modulators such oxidative stress (OS), inflammation and alterations of the endogenous antioxidative response system (ARE) regulated by the nuclear factor erythroid 2-related factor (Nrf2). Preclinical studies have also shown that nicotine (the principal e-liquid's ingredient used in e-cigarettes) can also cause OS, exacerbation of cerebral ischemia and secondary brain injury. Preliminary data from our laboratories provides evidence that likewise to TS; chronic e-Cigarette (e-Cig) vaping can promote loss of BBB integrity and vascular inflammation as well as act as a risk factor for the onset of stroke and worsening of post- ischemic brain injury. In addition, recent reports have shown that metformin (MF) treatment before and after ischemic injury reduce stress and inhibit inflammatory responses. Preliminary data provided in this grant suggests that MF promotes Nrf2-mediated counteractive mechanisms which drastically reduce TS toxicity at the brain and cerebrovascular levels while protecting BBB integrity. We provide additional in vivo evidence showing that MF can effectively reduce the oxidative and inflammatory risk for stroke and attenuate post-ischemic brain injury promoted by TS and e-Cig vaping. We propose that MF could be repurposed to prevent/reduce BBB damage and subsequent stroke injury by TS and e-Cig exposure in chronic smokers/vapors. Thus, the objectives of our study are: 1) Assess and validate the brain microvascular molecular mechanisms by which MF can protect the BBB from TS/e-Cig including ischemic/reperfusion (IR) injury. We will unravel the molecular target through which MF can positively impact the BBB and reduce the burden of ischemic stroke and cerebrovascular impairments in chronic smokers and vapors. 2) Evaluate in vivo the effect of prophylactic versus therapeutic (post-ischemic) administration of metformin in reducing TS/e-Cig - promoted cerebrovascular impairment and/or post-ischemic neuronal damage. In vivo investigations will define a mechanism of BBB transport and CNS entry for MF along with major ischemic injury endpoints; including infarction and edema volume, histological endpoints and behavioral recovery after stroke. Ultimately, we will characterize MF's efficacy and therapeutic time window for stroke treatment in mice exposed to TS or e-Cig vapor.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $568,452 )
2024	2024	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/12/2024	NON-COMPETING CONTINUATION	$568,452
														Subtotal = $568,452

Issue Date FY: 2023 ( Subtotal = $586,033 )
2023	2023	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/25/2023	NON-COMPETING CONTINUATION	$586,033
														Subtotal = $586,033

Issue Date FY: 2022 ( Subtotal = $586,033 )
2022	2022	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/27/2022	NON-COMPETING CONTINUATION	$586,033
														Subtotal = $586,033

Issue Date FY: 2021 ( Subtotal = $586,033 )
2021	2021	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/22/2021	NON-COMPETING CONTINUATION	$586,033
														Subtotal = $586,033

Issue Date FY: 2020 ( Subtotal = $595,334 )
2020	2020	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/26/2020	NEW	$595,334
														Subtotal = $595,334

Grand Total All Awards = $2,921,885

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Repurposing Metformin to Offset Stroke Risk and Injury in Comorbid Populations of Smokers

Award Number: R01NS117906

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer