A Mouse Model of Post-Stroke Pneumonia Induced by Intra-Tracheal Inoculation with <b><i>Streptococcus pneumoniae</i></b>

Abstract

Background: Stroke-induced immunodeficiency increases the risk of infectious complications, which adversely affects neurological outcome. Among those, pneumonia affects as many as one third of stroke patients and is the main contributor to mortality in the post-acute phase of stroke. Experimental findings on post-stroke susceptibility to spontaneous pneumonia in mice are contradictory. Here, we established a mouse model inducing standardized bacterial pneumonia and characterized the impaired pulmonary cellular and humoral immune responses after experimental stroke. Methods: Bacterial pneumonia was induced by intra-tracheal inoculation with Streptococcus pneumoniae at different time points after transient middle cerebral artery occlusion (MCAO). Bacterial counts in lungs and blood, histological changes, and cytokine production in the lungs were assessed. Furthermore, we investigated the effect of pneumonia on stroke outcome. Results: Intra-tracheal inoculation resulted in reproducible pneumonia and bacteraemia, and demonstrated post-stroke susceptibility to streptococcal pneumonia developing with a delay of at least 24 h after MCAO. Higher bacterial counts in mice infected 3 days after stroke induction correlated with reduced neutrophil and macrophage infiltration in the lungs and lower levels of pro-inflammatory cytokines in the broncho-alveolar lavage compared to sham-operated animals. Pneumonia increased mortality without affecting brain-infiltrating leukocytes. Conclusions: In this standardized mouse model of post-stroke pneumonia, we describe attenuated leukocyte infiltration and cytokine production in response to bacterial infection in the lungs that has a profound effect on outcome.

Relationship Between Blood Pressure Levels on Admission and the Onset of Acute Pneumonia in Elderly Patients With Cerebral Hemorrhage

“…In the acute phase of cerebral hemorrhage and cerebral infarction, adrenaline and noradrenaline concentrations in the blood and cerebrospinal fluid are known to increase due to the sympathetic nervous system being overactive [11]. Moreover, a report indicates that immunity decreased due to overactivity of the sympathetic nervous system in the stroke model using mice [12,13]. Overactivity of the sympathetic nervous system triggered by the onset of cerebral hemorrhage induces increased catecholamine concentration, leading to increased blood pressure, followed by the patients becoming even more vulnerable to develop pneumonia, because their immunity is decreased.…”

Efficacy and safety of intratracheal IFN-γ treatment to reverse stroke-induced susceptibility to pulmonary bacterial infections

“…In line with clinical observations, experimental stroke in mice also results in spontaneously developing pneumonia within 3 days after stroke (Prass et al, 2003). To improve the reproducibility of pneumonia in mice, an aspirationinduced pneumococcal pneumonia after stroke was established, demonstrating that MCAo in mice leads to an increased susceptibility to aspiration-induced S. pneumoniae infections (Mracsko et al, 2017;Prass et al, 2006). Here, we tested the hypothesis that IFN-γ treatment reconstitutes the pulmonary immune response and prevents spontaneous pneumonia as well as improves the clearance of induced pneumococcal pneumonia after experimental stroke.…”

Impact of Key Nicotinic AChR Subunits on Post-Stroke Pneumococcal Pneumonia

“…This time window has been used in aspiration-induced post-stroke pneumonia models using a low number of S. pneumoniae capable of inducing severe pneumonia with high bacterial burden in lung of MCAo but not sham animals [ 19 ]. Moreover, bacterial burden in lung was lower at day two compared to day one after inoculation [ 56 ]. Since naïve mice require usually 24 h to clear induced infection, we used this time point to assess immune parameters and bacterial burden after inoculation of S. pneumoniae .…”