ro13-9904 and Subarachnoid-Hemorrhage

A 77-year-old man visited our hospital with unstable gait following 2 months of anorexia. Brain MRI showed multiple infarcts; cardiac echocardiography revealed mitral-valve vegetation; and blood culture revealed methicillin-resistant coagulase-negative staphylococci. The patient was diagnosed with infective endocarditis (IE). Subarachnoid hemorrhage (SAH) developed ten days after antibiotic treatment. Intracranial aneurysm was not found. We speculated that chronic inflammation of the cerebral arterial walls by bacteria of low virulence was associated with SAH complication. The vegetation disappeared following additional gentamicin administration and the patient recovered to walk.

Topics: Aged; Anti-Bacterial Agents; Ceftriaxone; Echocardiography, Transesophageal; Endocarditis; Gentamicins; Humans; Magnetic Resonance Imaging; Male; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Treatment Outcome; Vancomycin

Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by a reduction in excitatory amino acid transporter 2 (EAAT2) expression and severe amino acid excitotoxicity. The aim of this study was to explore the neuroprotective effect of ceftriaxone (CEF), a potent compound that up-regulates EAAT2, against EBI and the potential mechanisms using in vitro experiments and a rat model of SAH. Intracisternal treatment with CEF significantly improved neurological outcomes and alleviated extracellular glutamate accumulation after SAH. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining and Western blot analysis of cleaved caspase 3 showed that CEF decreased hippocampal neuronal apoptosis following SAH. Immunofluorescent staining and Western blotting revealed that CEF significantly reversed the down-regulation of EAAT2 expression following SAH. In Morris water maze (MWM) tests, CEF remarkably ameliorated the SAH-induced cognitive dysfunction in spatial learning memory and reference memory. CEF promoted the nuclear translocation of p65 as well as the activation of Akt in hippocampal astrocytes in vitro and in vivo. These findings suggest that CEF may exert significant protective effects against EBI following SAH by modulating the PI3K/Akt/NF-κB signaling pathway.

Topics: Animals; Apoptosis; Astrocytes; Brain Injuries; Caspase 3; Ceftriaxone; Cells, Cultured; Cognition Disorders; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Glutamic Acid; Hippocampus; Male; Neoplasm Proteins; Neurons; Neuroprotective Agents; NF-kappa B; Nucleocytoplasmic Transport Proteins; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage