Lipopolysaccharide Induces Subacute Cerebral Microhemorrhages with Involvement of Nitric Oxide Synthase in Rats

Background: Cerebral microhemorrhage (CMH) is a neuropathological term that could be easily found in cerebral amyloid angiopathy, intracerebral hemorrhages, etc. CMHs could be detected clearly in vivo by magnetic resonance imaging (MRI)-susceptibility-weighted imaging or MRI T2* scan. This terminology is now accepted in the area of neuroimaging. CMHs are quite common in elderly patients and are associated with several other neuropsychiatric disorders. The causes of CMHs are complicated, and neuroinflammation is considered as one of the well-accepted mechanical factors. This study investigated whether lipopolysaccharide (LPS)-induced CMHs occur through the regulation of nitric oxide synthase (NOS) isoforms and reveals the exact underlying mechanism of LPS-induced CMHs. Methods: Our work successfully developed a subacute model of CMHs in rats. LPS was intraperitoneally injected into rats at 0, 6, and 24 hours, which induced typical CMH features 7 days after the injection. These could be detected on the brain surface or parenchyma by hematoxylin and eosin staining and MRI. Results: LPS-treated rats showed significant activation of astrocytes and microglia, as well as loss of pericytes and disruption of blood-brain barrier. Meanwhile, both astrocytes and microglia were positively correlated with CMH numbers. Furthermore, the expressions of NOS isoforms were also examined, and the levels of neuronal NOS and endothelial NOS were found to be elevated. Conclusions: These results implied that the NOS isoforms might be involved in the subacute model of CMHs in rats induced by LPS.