Bacterial Peptidoglycan and Leukocyte Reactivity in the Brain Following Ischaemic Stroke

Abstract

It has recently been reported that bacteria found in the brain of neurodegenerative diseases, such as Alzheimer’s and amyotrophic lateral sclerosis, may cause neuroinflammation. Whilst infiltrating immune cells into brain are a key contributor to the pathophysiology of ischaemic stroke, whether or not this is due to the presence of bacteria within the brain remains to be determined. Therefore, the aim of this study was to establish whether peptidoglycan positive bacteria located within the ischaemic hemisphere post‐stroke attract infiltrating immune cells. To test this aim, C57BL6 male mice (8–12 weeks old) were subjected to either photothrombotic stroke (n=16), 0.5 h middle cerebral artery occlusion (MCAO, n=12) or sham surgery (n=12). Functional tests assessing motor function were conducted pre‐surgery, 24 h and/or 72 h post‐surgery. Infarct volume was assessed at 24 or 72 h post‐stroke via thionin staining and infiltrating immune cells within the brain were identified by immunofluorescence. Photothrombosis or MCAO caused significant functional impairment, as determined by the hanging wire and cylinder tests, compared to sham (P<0.05). Photothrombotic stroke caused cortical infarct damage whereas MCAO induced hypothalamic, thalamic, hippocampal and cortical infarct damage. Peptidoglycan immunoreactivity was observed within the infarct core of both ischaemic stroke models at 24 and 72 h post‐surgery. Whilst infiltrating myeloperoxidase‐positive neutrophils were located in close proximity with peptidoglycan‐positive cells at 24 h post‐stroke, F4/80‐positive macrophages were co‐localised with peptidoglycan‐positive cells at 72 h post‐stroke. Collectively, these data suggest that bacteria located in the infarct core following cerebral ischaemia may trigger an immune response, and thus could be a therapeutic target for stroke patients.