Colonic bacterial translocation as a possible factor in stress-worsening experimental stroke outcome

Abstract

Stress is known to be one of the risk factors of stroke, but only a few experimental studies have examined the possible mechanisms by which prior stress may affect stroke outcome. In stroke patients, infections impede neurological recovery and increase morbidity as well as mortality. We previously reported that stress induces a bacterial translocation and that prior immobilization stress worsens experimental stroke outcome through mechanisms that involve inflammatory mediators such as release of proinflammatory cytokines and enzyme activation. We now investigate whether bacterial translocation from the intestinal flora of rats with stress before experimental ischemia is involved in stroke outcome. We used an experimental paradigm consisting of exposure of Fischer rats to repeated immobilization sessions before permanent middle cerebral artery occlusion (MCAO). The presence of bacteria and the levels and expression of different mediators involved in the bacterial translocation were analyzed. Our results indicate that stress before stroke is related to the presence of bacteria in different organs (mesenteric nodes, spleen, liver, and lung) after MCAO and increases inflammatory colonic parameters (such as cyclooxygenase-2, inducible nitric oxide synthase, and myeloperoxidase), but decreases colonic immunoglobulin A, and these results are correlated with colonic inflammation and bacterial translocation. Understanding the implication of bacterial translocation during stress-induced stroke worsening is of great potential clinical relevance, given the high incidence of infections after severe stroke and their main role in mortality and morbidity in stroke patients.

A Novel SPECT-Based Approach Reveals Early Mechanisms of Central and Peripheral Inflammation after Cerebral Ischemia

“…Constipation, dysphagia, paralytic ileus, digestion problems, and other gut symptoms are often seen in stroke patients and bacterial translocation across the gut epithelium has also been reported. [9][10][11]21,40 Since the gut barrier structures resemble those of the central nervous system 41 and 99 mTc-DTPA identified early, but transient changes in the gut after stroke, whereas no changes in I125-HSA or 99 mTc-HMPAO signal were observed, it is possible that 99 mTc-DTPA signal increases are reflective of changes in the gut barrier structures in response to brain injury. The autonomic nervous system has been implicated in the development of poststroke immunosuppression.…”

“…[9][10][11]21 However, no in vivo imaging studies showed previously that acute brain injury results in robust and rapid changes in the gut and gave insight into the mechanisms. The SPECT imaging with 99mTc-DTPA revealed early and transient changes in the gut after experimental stroke as identified by increases in DTPA signal 2 hours after reperfusion (by 64%, P = 0.025, Figures 5A and 5C), which recovered fully by Twenty-four hours after MCAo, DTPA signal intensity in the striatum correlates significantly with BBB injury as measured by IgG staining on brain sections.…”

The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke

“…In a rat MCAo model, bacteria translocated from the gut to extraintestinal organs after stroke, which might trigger systemic inflammatory response or even cause poststroke infections [61]. Additionally, stress before stroke might boost bacterial translocation from the intestine into the bloodstream [62]. A recent study demonstrated alterations in microbiota profile after severe cerebral ischemia and linked poststroke dysbiosis with induction of proinflammatory immune response.…”

Translocation of gut flora and its role in sepsis

“…Strong colonic infl ammatory response and alteration of colonic epithelial barrier leads to increased mucosal permeability [32] and thereby bacterial translocation.…”