Hyperbaric Oxygen Treatment Ameliorates Hearing Loss and Auditory Cortex Injury in Noise Exposed Mice by Repressing Local Ceramide Accumulation.

Noise-induced hearing loss (NIHL) relates closely to auditory cortex (AC) injury, so countermeasures aiming at the AC recovery would be of benefit. In this work, the effect of hyperbaric oxygen treatment on NIHL was elucidated, which was imposed on mice before (HBOP), during (HBOD) or after (HBOA) noise exposure. Morphology of neurons was assayed by hematoxylin-eosin or Nissl staining. Ceramide (Cer) level was measured through immunohistochemistry analysis. Apoptotic neurons were counted using transferase-mediated dUTP nick end labeling (TUNEL) staining. We demonstrated that the intense, broad band noise raised the threshold of auditory brainstem response, evoked neuronal degeneration or apoptosis and triggered the Cer accumulation in AC, all of which were restored significantly by HBOP, but not HBOD or HBOA. Cer over-generation reversed the advantages of HBOP significantly, while its curtailment recapitulated the effect. Next, noise exposure raised the superoxide or malondialdehyde (MDA) production which was blocked by HBOP or Cer repression. Oxidative control not only attenuated the hearing loss or neurodegeneration but, in turn, reduced the Cer formation significantly. In summary, mutual regulation between Cer and oxidative stress underlies the HBOP's curative effect on hearing loss and neuronal damage in noise-exposed mice.

Effects of hyperbaric oxygen on hippocampal neuronal apoptosis in rats with acute carbon monoxide poisoning.

INTRODUCTION: Acute carbon monoxide (CO) poisoning causes serious health problems such as neuropsychological sequelae. This study aimed to investigate neuronal apoptosis and the effects of hyperbaric oxygen (HBO2) on different regions of the rat hippocampus after CO poisoning. METHODS: 90 mature male Sprague Dawley rats were randomly divided into three groups: the normal control group (NC group), the acute carbon monoxide-poisoned group (CO group) and the hyperbaric oxygen treatment group (HBO2 group). CO exposure included 0, 1, 3, 7, 14 and 21 treatment days, one exposure on the first day, and sacrifice on each of the following days. HBO2 exposure included treatment for 0, 1, 3, 7, 14 and 21 days, daily treatment after CO exposure, and sacrifice after the last HBO2 treatment on each of those days. Hematoxylin-eosin staining, immunohistochemical staining, immunofluorescence staining, and western blot analysis were performed to detect apoptosis in brain tissue samples. RESULTS: MMP-9 and caspase-3 were prominently increased by CO exposure and inhibited by HBO2 in the CA3 region in the hippocampus at one, three and seven days (immunohistochemical staining [IHC]: P ⟨ 0.05). Neu N and the ratio of Bcl-2/ BAX were prominently decreased by CO exposure and rescued by HBO2 in the CA3 region after seven days of treatment (IHC: P ⟨ 0.05). CONCLUSION: These findings indicated that neuronal apoptosis in the rat hippocampus could be induced by acute CO exposure, especially in the CA3 region. HBO2 could effectively inhibit neuronal apoptosis, especially in the CA3 region after seven days of treatment. The application of HBO2 to inhibit MMP-9 and apoptosis may contribute to brain recovery after acute CO poisoning.

Doxepin Mitigates Noise-induced Neuronal Damage in Primary Auditory Cortex of Mice via Suppression of Acid Sphingomyelinase/Ceramide Pathway.

Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over-activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved. The mice were exposed to noise with frequencies of 20-20 KHz and intensity of 95 dB. Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 mg kg-1  days-1 . Morphology of neurons was examined using hematoxylin-eosin (HE) and Nissl staining. Apoptosis was assayed through transferase-mediated dUTP nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was detected by western blot and immunohistochemistry analysis. We demonstrated intense, broad band noise caused upward shift of auditory brainstem response (ABR) threshold to sound over frequencies 4-32 KHz, with prominent morphologic changes and enhanced apoptosis in neurons of primary auditory cortex (A1) (P < 0.05). DOX partly restored noise-caused hearing loss alleviating morphologic changes or apoptosis remarkably (P < 0.05). Both ASM and Cer abundance were elevated significantly by noise which was reversed upon DOX treatment (P < 0.05), but neither noise nor DOX altered AC content. DOX had no influence on hearing, neuronal morphology or ASM/Cer in control mice. Our result suggests DOX palliates noise induced hearing loss and neuronal damage in auditory cortex by correcting over-activation of ASM/Cer without hampering intrinsic behavior of it. Anat Rec, 300:2220-2232, 2017. © 2017 Wiley Periodicals, Inc.

[Transcutaneous electrical nerve stimulation improves oppilative symptoms and increases colonic transit in patients with slow transit constipation].

OBJECTIVE: To evaluate the therapeutic value of transcutaneous electrical nerve stimulation (TENS) at acupoints in slow transit constipation (STC). METHODS: Thirty-nine patients with (STC) who met the Rome III diagnostic criteria, were randomly assigned to 2 groups: TENS treatment group including 2 males and 18 females, aged (46 +/- 14), undergoing TENS at the acupoints ST36 (Zusanli) and PC6 (Neiguan) twice a day, 30 min after breakfast and 30 min before going to bed, for 2 weeks, and control group, including 2 males and 17 females, undergoing sham TENS treatment at 2 sham acupoints. Questionnaire survey was conducted to investigate the dyschezia scores. Self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to assess the depression and anxiety status. X-ray examination with barium strips, radio-opaque marker, was used to detect the colonic transit status. RESULTS: (1) The dyschezia symptom total score after treatment in the TENS treatment group was (9.05 +/- 0.58), significantly lower than that before treatment (18.30 +/- 0.45, P < 0.01), and the oppilative symptom total score after the sham treatment of the control group was (18.00 +/- 0.46), not significantly different from that before the treatment (18.03 +/- 0.45, P > 0.05). (2) The number of vestigial barium strips of the TENS treatment group was (7.2 +/- 1.2), significantly lower than that before treatment (15.1 +/- 1.1, P < 0.01), and the change was especially obvious in the colon sector (3.3 +/- 0.8 vs 11.0 +/- 1.0, P < 0.01). However, there was no significant difference in the number of barium strips in the control group before and after the sham treatment. (3) The score of SDS and SAS of the TENS treatment group after the treatment were 34.7 +/- 0.9 and (43.7 +/- 1.5 respectively, both significantly lower than those before the treatment (37.3 +/- 0.9 and 48.1 +/- 1.8 respectively, both P < 0.05), however, there were not significant differences in the SDS and SAS scores before and after the sham treatment in the control group. CONCLUSION: TENS at the acupoints Zusanli and Neiguan is capable of improving the oppilative symptoms and ameliorating anxiety and depression state, promoting colonic transit in STC patients.

[Influences of repeated lower +Gz exposures on high +Gz exposure induced brain injury in rats].

Objective. To explore the influence of repeated lower +Gz exposures on high +Gz exposure induced brain injury in rats. Method. Forty SD male rats were randomly divided into control group (5 rats), +10 Gz/5 min group (5 rats) +4 Gz exposure one time, three times and five times group (10 rats each group). After 1 d or 6 d of +4 Gz exposure each group were exposed to +10 Gz again. Three days after +10 Gz exposure the neuron damage was observed by light microscope in HE stained section. Result. There was no brain damage after repeated +4 Gz/3 min exposure 5 times so it was reasonable to use this exposure intensity as ischemia stimulation. +10 Gz/5 min exposure could result in irreversible neuron damage such as neuron degeneration and coagulation necrosis. The experiment results suggested that after +10 Gz/5 min exposure there were degenerated neurons in cortex, hippocampus and thalamus. The number of degenerated neurons were obviously decreased in cortex, hippocampus and thalamus when exposed to +10 Gz/5 min again after repeated +4 Gz/3 min 3-5 times. Conclusion. The degree of neuron damage was obviously slight at the time of exposure to +10 Gz/5 min again after repeated +4 Gz/3 min 3-5 times. The ischemia tolerance at the time of exposure to +Gz was similar to other brain ischemia.