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We report here the effects of hydrogen sulfide (sulfide), that accumulates in ETHE1 deficiency, in rat cerebellum. Sulfide impaired electron transfer and oxidative phosphorylation. Sulfide also induced mitochondrial swelling, and decreased ΔΨm and calcium retention capacity in cerebellum mitochondria, which were prevented by cyclosporine A (CsA) plus ADP, and ruthenium red, suggesting mitochondrial permeability transition (mPT) induction. Melatonin (MEL) and N-ethylmaleimide also prevented sulfide-induced alterations. Prevention of sulfide-induced decrease of ΔΨm and viability by CsA and MEL was further verified in cerebellum neurons. The data suggest that sulfide induces mPT pore opening via thiol modification and ROS generation., (Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

We experienced two cases of brain abscess secondary to middle ear cholesteatoma. One, a 61-year-old woman, presented with left otalgia, appetite loss and nausea. The computed tomography obtained on admission revealed a middle ear cholesteatoma. The magnetic resonance image showed the presence of a brain abscess in the cerebellum. The brain abscess was drained and the cholesteatoma was removed using the canal down procedure under general anesthesia. Part of the cholesteatoma invaded the posterior cranial fossa was could not be removed from the otological surgical field. The patient has been under observation as an outpatient for 6 months already and no abnormal signs have been detected. The other patient, a 55-year-old man, was admitted to our hospital for a detailed examination because he had right otalgia and progressive headache. The examination of spinal fluid obtained by lumbar puncture showed marked elevation of the white blood cells count. Computed tomography revealed a middle ear cholesteatoma. The magnetic resonance image obtained on admission showed an area of low-intensity encapsulated by an area of high-intensity in the right temporal lobe. The abscess was drained and the cholesteatoma was removed using the canal down procedure under general anesthesia. The patient has been under observation for 1 year already and has presented no signs of recurrence.

Nuclear factor-kappaB (NF-kappaB) is a critical regulator of many genes involved in the pathogenesis of bacterial meningitis. Recently, activation of NF-kappaB was shown to be a key event in the inflammatory host response and the development of intracranial complications during experimental pneumococcal meningitis. Since the p50 subunit of NF-kappaB lacks a transactivation domain and can therefore act as a transcriptional repressor, we investigated whether NF-kappaB1 (p50) exerts anti-inflammatory effects in pneumococcal meningitis. p50-deficient mice had higher cerebellar pneumococcal titers (10.06+/-0.47 vs. 8.51+/-1.06 log colony-forming units [cfu]/cerebellum), cerebrospinal fluid (CSF) leukocyte counts (11,475+/-2340 vs. 8444+/-1405 cells/microl) and brain concentrations of interleukin-1beta (125.9+/-50.3 vs. 58.5+/-52.2 pg/mg protein) than their wild-type littermates. With ceftriaxone therapy, none of the wild-type mice but 43% of the p50-deficient animals died. In conclusion, lack of NF-kappaB1 (p50) was associated with impaired bacterial clearing, enhanced inflammatory host response and increased mortality during pneumococcal meningitis.

During meningitis, the host produces a plethora of signaling agents as part of a coordinated defense mechanism against invading pathogens. Nitric oxide (NO) and prostaglandin E2 (PGE2) are two such inflammatory mediators produced in response to bacterial endotoxins. Disruption of the blood-brain barrier (BBB) is one of many pathophysiological consequences of meningitis. The present objective was to examine the time-course of NO and PGE2 production in relationship to BBB permeability alterations during experimentally-induced meningitis. Meningeal inflammation was elicited by intracisternal administration of the bacterial endotoxin, lipopolysaccharides (LPS; 200 microg), and NO, PGE2, and BBB integrity were monitored over the next 24 h. Meningeal NO production was assessed by headspace chemiluminescence; cerebrospinal fluid PGE2 was determined by enzyme-linked immunosorbent assay (ELISA) immunoassay; and BBB integrity was determined by the brain accumulation of 14C-sucrose. Similar time-course profiles for NO and PGE2 were observed, with a peak effect for both inflammatory mediators observed within 6-8 h after intracisternal LPS dosing. Statistically significant (p < 0.05) disruption of the BBB was observed in various brain regions. Strikingly similar temporal relationships were observed for NO and PGE2 production and BBB disruption. These results suggest the hypothesis that NO and PGE2 may act in conjunction to disrupt the BBB during experimental meningitis.