NDLI: Stabilizing histamine release in gut mast cells mitigates peripheral and central inflammation after stroke

Content Provider	Springer Nature : BioMed Central
Author	Conesa, Maria P. Blasco Blixt, Frank W. Peesh, Pedram Khan, Romeesa Korf, Janelle Lee, Juneyoung Jagadeesan, Gayathri Andersohn, Alexander Das, Tushar K. Tan, Chunfeng Di Gesu, Claudia Colpo, Gabriela Delevati Moruno-Manchón, Jose Félix McCullough, Louise D. Bryan, Robert Ganesh, Bhanu P.
Abstract	Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and improve stroke outcomes. We used the transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18 mo) male mice to investigate the role of MC in neuroinflammation post-stroke. After MCAO we treated mice with 25 mg/kg body weight of cromolyn (MC stabilizer) by oral gavage. Cromolyn was administered at 3 h, 10 h, 24 h and every 24 h for 3 days post-stroke. Three control groups were used. One group underwent a sham surgery and was treated with cromolyn, one received sham surgery with PBS vehicle and the third underwent MCAO with PBS vehicle. Mice were euthanized at 24 h and 3 days post-stroke. Cromolyn administration significantly reduced MC numbers in the brain at both 24 h and 3 days post-stroke. Infarct volume was not significantly different between groups, however improved functional outcomes were seen at 3 days post-stroke in mice that received cromolyn. Treatment with cromolyn reduced plasma histamine and IL-6 levels in both the 24-h and 3-day cohorts. Gut MCs numbers were significantly reduced after cromolyn treatment at 24 h and 3 days after stroke. To determine if MC trafficking from the gut to the brain occurred after injury, GFP+MCs were adoptively transferred to c-kit−/− MC knock-out animals prior to MCAO. 24 h after stroke, elevated MC recruitment was seen in the ischemic brain. Preventing MC histamine release by cromolyn improved gut barrier integrity and an improvement in stroke-induced dysbiosis was seen with treatment. Our results show that preventing MC histamine release possesses prevents post-stroke neuroinflammation and improves neurological and functional outcomes. Graphical abstract
Related Links	https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-023-02887-7.pdf
Ending Page	20
Page Count	20
Starting Page	1
File Format	HTM / HTML
ISSN	17422094
DOI	10.1186/s12974-023-02887-7
Journal	Journal of Neuroinflammation
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2023-10-07
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Neurobiology Immunology Histamine Mast cells Stabilizer Gut–brain axis Neuroinflammation Cytokines Peripheral factors Microbiome
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology Cellular and Molecular Neuroscience Neurology
Journal Impact Factor	9.3/2023
5-Year Journal Impact Factor	9.8/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation

Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice

Reduced gut microbiome protects from alcohol-induced neuroinflammation and alters intestinal and brain inflammasome expression

Neuro-inflammation, blood-brain barrier, seizures and autism

Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer’s disease-like neuroinflammation triggered by periodontal disease

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

New perspectives on central and peripheral immune responses to acute traumatic brain injury

Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer’s disease

Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease

Stabilizing histamine release in gut mast cells mitigates peripheral and central inflammation after stroke

Similar Documents

Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation

Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice

Reduced gut microbiome protects from alcohol-induced neuroinflammation and alters intestinal and brain inflammasome expression

Neuro-inflammation, blood-brain barrier, seizures and autism

Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer’s disease-like neuroinflammation triggered by periodontal disease

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

New perspectives on central and peripheral immune responses to acute traumatic brain injury

Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer’s disease

Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease

Stabilizing histamine release in gut mast cells mitigates peripheral and central inflammation after stroke