scholarly journals Oral Administration of Brain Protein Combined With Probiotics Induces Immune Tolerance Through the Tryptophan Pathway

2021 ◽  
Vol 14 ◽  
Author(s):  
Yongxin Hou ◽  
Lixia Xu ◽  
Sirong Song ◽  
Weijia Fan ◽  
Qiaoli Wu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Oral Administration ◽  
Immune Tolerance ◽  
Tryptophan Hydroxylase ◽  
Intestinal Barrier ◽  
Brain Protein ◽  
Aryl Hydrocarbon ◽  
Tandem Mass Tag ◽  
Tryptophan Pathway ◽  
Surgical Brain Injury

Excessive inflammation leads to secondary immune damage after traumatic brain injury (TBI). The intestinal mucosa is a key component of immune tolerance due to gut-brain axis regulation, but the curative effect is not optimal. Intestinal dysfunction impairs the establishment of immune tolerance in patients with TBI. Therefore, we orally administered brain protein (BP) combined with probiotics to induce immune tolerance and explored the mechanism by which the homeostasis of the microbiota contributes to the enhancement of curative effects by BPs. Herein, we demonstrated that patients with TBI and surgical brain injury (SBI) models of rats had obvious dysbiosis. Notably, the intestinal barrier, proinflammatory cytokines, and activation of microglia demonstrated that excessive inflammatory damage was better controlled in the combined group (oral administration of BP combined with probiotics) than in the BP group (oral administration of BP). Fundamentally, tandem mass tag (TMT)-based quantitative proteomics analysis revealed that BP and probiotics preferentially affect Try-related pathways. A series of experiments further confirmed that Indoleamine 2,3 dioxygenase (IDO)/Kynurenine (Kyn)/Aryl hydrocarbon receptor (AhR) expression was high in the BP group, while Tryptophan hydroxylase 1(TpH1)/5-hydroxytryptamine (5-HT) only changed in the combined group. This study suggests that probiotics can enhance the efficacy of oral BP-induced immune tolerance through the Try pathway.

scholarly journals The Effect of Acute Oral Galactose Administration on the Redox System of the Rat Small Intestine

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 37
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Davor Virag ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Small Intestine ◽  
Oral Administration ◽  
Redox Homeostasis ◽  
Intestinal Barrier ◽  
Redox System ◽  
Dissociation Rate ◽  
Term Administration ◽  
Male Wistar Rats

Galactose is a ubiquitous monosaccharide with important yet incompletely understood nutritive and physiological roles. Chronic parenteral d-galactose administration is used for modeling aging-related pathophysiological processes in rodents due to its ability to induce oxidative stress (OS). Conversely, chronic oral d-galactose administration prevents and alleviates cognitive decline in a rat model of sporadic Alzheimer’s disease, indicating that galactose may exert beneficial health effects by acting in the gut. The present aim was to explore the acute time-response of intestinal redox homeostasis following oral administration of d-galactose. Male Wistar rats were euthanized at baseline (n = 6), 30 (n = 6), 60 (n = 6), and 120 (n = 6) minutes following orogastric administration of d-galactose (200 mg/kg). The overall reductive capacity, lipid peroxidation, the concentration of low-molecular-weight thiols (LMWT) and protein sulfhydryls (SH), the activity of Mn and Cu/Zn superoxide dismutases (SOD), reduced and oxidized fractions of nicotinamide adenine dinucleotide phosphates (NADPH/NADP), and the hydrogen peroxide dissociation rate were analyzed in duodenum and ileum. Acute oral administration of d-galactose increased the activity of SODs and decreased intestinal lipid peroxidation and nucleophilic substrates (LMWT, SH, NADPH), indicating activation of peroxidative damage defense pathways. The redox system of the small intestine can acutely tolerate even high luminal concentrations of galactose (0.55 M), and oral galactose treatment is associated with a reduction rather than the increment of the intestinal OS. The ability of oral d-galactose to modulate intestinal OS should be further explored in the context of intestinal barrier maintenance, and beneficial cognitive effects associated with long-term administration of low doses of d-galactose.

scholarly journals Preoperative mucosal tolerance to brain antigens and a neuroprotective immune response following surgical brain injury

2012 ◽  
Vol 116 (1) ◽  
pp. 246-253 ◽  
Author(s):  
Robert E. Ayer ◽  
Nazanin Jafarian ◽  
Wanqiu Chen ◽  
Richard L. Applegate ◽  
Austin R. T. Colohan ◽  
...  
Keyword(s):  
Brain Injury ◽  
Myelin Basic Protein ◽  
Cerebral Edema ◽  
Transforming Growth Factor ◽  
Basic Protein ◽  
Immunological Tolerance ◽  
Neurological Injury ◽  
Mucosal Tolerance ◽  
Surgical Brain Injury

Object Intracranial surgery causes cortical injury from incisions, hemorrhage, retraction, and electrocautery. The term “surgical brain injury” (SBI) has been developed to categorize this injury inherent to the procedure. Neuroinflammation plays a significant role in SBI. Traditional antiinflammatory therapies are often limited by their immunosuppressive side effects and poor CNS penetration. This study uses mucosal tolerance to develop an immune system that is tolerant to brain myelin basic protein (MBP) so that inflammation can be suppressed in a timely and site-specific manner following surgical disruption of the blood-brain barrier. Methods A standard SBI model using CD57 mice was used. Nasopharyngeal mucosa was exposed to vehicle, ovalbumin, or MBP to develop mucosal tolerance to these antigens. Immunological tolerance to MBP was confirmed in vivo through hypersensitivity testing. Neurological scores, cerebral edema, and interleukin (IL)–1β and transforming growth factor (TGF)–β1 cytokine levels were measured 48 hours postoperatively. Results Hypersensitivity testing confirmed the development of immune tolerance to MBP. Myelin basic protein–tolerant mice demonstrated reduced neurological injury, less cerebral edema, decreased levels of IL-1β, and increased levels of TGFβ1 following SBI. Conclusions Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI.

Oral administration of a casein matrix containing β-casofensin protects the intestinal barrier in two preclinical models of gut diseases

2016 ◽  
Vol 27 ◽  
pp. 223-235 ◽  
Author(s):  
Claudine Bessette ◽  
Gwénaële Henry ◽  
Soraya Sekkal ◽  
Bérengère Benoit ◽  
Jérémie Bruno ◽  
...  
Keyword(s):  
Oral Administration ◽  
Intestinal Barrier ◽  
Preclinical Models

Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury

2016 ◽  
pp. 317-321
Author(s):  
Devin W. McBride ◽  
Yuechun Wang ◽  
Loic Adam ◽  
Guillaume Oudin ◽  
Jean-Sébastien Louis ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Edema ◽  
Sensorimotor Deficits ◽  
Surgical Brain Injury
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