Inhalation of hydrogen gas mitigates sevoflurane-induced neuronal apoptosis in the neonatal cortex and is associated with changes in protein phosphorylation.

Inhalation of hydrogen (H2) gas is therapeutically effective for cerebrovascular diseases, neurodegenerative disorders, and neonatal brain disorders including pathologies induced by anesthetic gases. To understand the mechanisms underlying the protective effects of H2 on the brain, we investigated the molecular signals affected by H2 in sevoflurane-induced neuronal cell death. We confirmed that neural progenitor cells are susceptible to sevoflurane and undergo apoptosis in the retrosplenial cortex of neonatal mice. Co-administration of 1-8% H2 gas for 3 h to sevoflurane-exposed pups suppressed elevated caspase-3-mediated apoptotic cell death and concomitantly decreased c-Jun phosphorylation and activation of the c-Jun pathway, all of which are induced by oxidative stress. Anesthesia-induced increases in lipid peroxidation and oxidative DNA damage were alleviated by H2 inhalation. Phosphoproteome analysis revealed enriched clusters of differentially phosphorylated proteins in the sevoflurane-exposed neonatal brain that included proteins involved in neuronal development and synaptic signaling. H2 inhalation modified cellular transport pathways that depend on hyperphosphorylated proteins including microtubule-associated protein family. These modifications may be involved in the protective mechanisms of H2 against sevoflurane-induced neuronal cell death.

Ninjin'yoeito Modulates Baseline and Reperfusion-Induced Changes in the Arteriole Diameter and Blood Flow in the Cerebral Cortex of Anesthetized Mice.

OBJECTIVE: Intragastric administration of ninjin'yoeito (NYT), a traditional Japanese herbal medicine, reportedly prevents the decrease in baseline cerebral blood flow (CBF) in the cortex following gastric administration of water. We investigated the effect of NYT on baseline and dynamic changes in cerebral cortical arteriole diameter. METHODS: Urethane-anesthetized mice were intragastrically administered 1 g/kg NYT or distilled water (DW). The artery in the left parietal cortex was imaged using two-photon microscopy. The baseline diameter of penetrating arterioles was measured before and 50-60 min after administration. Dynamic CBF and arteriole diameter changes before, during, and after transient occlusion of the left common carotid artery were measured approximately 10 min after administration. RESULTS: DW decreased the baseline diameter of the penetrating arterioles, whereas NYT did not. During occlusion, the increase in penetrating arteriole diameter was comparable for DW and NYT; however, during reperfusion, the return to preocclusion diameter was slower for NYT than DW. Laser-speckle contrast imaging confirmed that CBF, although comparable during occlusion, was higher during reperfusion for NYT than DW. CONCLUSIONS: These results suggest that NYT attenuates vasoconstriction in penetrating arterioles after intragastric administration and during cerebral reperfusion, contributing to CBF regulation.

Excimer laser coronary atherectomy with distal protection for neoatherosclerosis rupture: a case report.

Background: Neoatherosclerosis, a prominent contributor to in-stent restenosis (ISR), persists as a formidable challenge during percutaneous coronary intervention. Excimer laser coronary atherectomy (ELCA) and embolic protection devices may help reduce coronary flow disturbance from procedure-related distal embolization. Case summary: A 71-year-old man experienced in-stent neoatherosclerosis rupture-related non-ST segment elevation myocardial infarction. Multidisciplinary intracoronary imaging, including intravascular ultrasound and optical coherence tomography (OCT), suggested that the ISR was caused by a neoatherosclerosis rupture that can potentially lead to distal embolization. Excimer laser coronary atherectomy (fluence, 45 mJ/mm2 and frequency, 25 pulse/s) using a 1.7 mm concentric catheter was performed with distal protection using Filtrap (Nipro Corporation, Tokyo, Japan), which significantly reduced the volume of the neoatherosclerosis. However, subsequent ELCA on the highest setting (fluence, 60 mJ/mm2 and frequency, 40 pulse/s) led to a filter no-reflow phenomenon, although OCT revealed a further effective vaporization of the neoatherosclerosis and an apparent reduction of soft tissue compatible with the thrombus. After removing the embolic protection device, drug-coated balloon angioplasty provided optimal results without coronary flow disturbance. Discussion: Excimer laser coronary atherectomy reduces soft plaque and thrombus burden, which can reduce the occurrence of distal embolization in select cases. In the case of this patient, procedure-related distal embolization may have been induced by the heightened photomechanical effects resulting from the use of the highest setting in ELCA under increased intracoronary arterial pressure caused by continuous saline injection during ELCA. Concomitant distal protection during ELCA may be more feasible for preventing coronary flow disturbance in patients with a large amount of neoatherosclerosis.

Identification of adrenergic presynaptic and postsynaptic protein locations at neuromuscular junctions, their decrease during aging, and recovery by nicotinamide mononucleotide administration.

Neuromuscular junctions are innervated by motor and sympathetic nerves. The sympathetic modulation of motor innervation shows functional decline during aging, but the cellular and molecular mechanism of this change is not fully known. This study aimed to evaluate the effect of aging on sympathetic nerves and synaptic proteins at mouse neuromuscular junctions. Sympathetic nerves, presynaptic, and postsynaptic proteins of sympathetic nerves at neuromuscular junctions were visualized using immunohistochemistry, and aging-related changes were compared between adult-, aged-, and nicotinamide mononucleotide (NMN) administered aged mice. Sympathetic nerves were detected by anti-tyrosine hydroxylase antibody, and presynaptic protein vesicular monoamine transporter 2 colocalized with the sympathetic nerves. These two signals surrounded motor nerve terminals and acetylcholine receptor clusters. Postsynaptic neurotransmitter receptor ß2-adrenergic receptors colocalized with motor nerve terminals and resided in reduced density at extrasynaptic sarcolemma. The signal intensity of the sympathetic nerve marker did not show a significant difference at neuromuscular junctions between 8.5-month-old adult mice and 25-month-old aged mice. However, the signal intensity of vesicular monoamine transporter 2 and ß2-adrenergic receptors showed age-related decline at neuromuscular junctions. Interestingly, both age-related declines reverted to the adult level after 1 month of oral administration of NMN by drinking water. In contrast, NMN administration did not alter the expression level of sympathetic marker tyrosine hydroxylase at neuromuscular junctions. The results suggest a functional decline of sympathetic nerves at aged neuromuscular junctions due to decreases in presynaptic and postsynaptic proteins, which can be reverted to the adult level by NMN administration.