A disintegrin and metalloproteinase 10 (ADAM10) plays an essential role in the regulation of survival, proliferation, migration, and differentiation of various neural cells. Nevertheless, the role of ADAM10 in oligodendrocyte precursors (OPCs) and myelination in the central nervous system (CNS) of developing and adult mouse brains is still unknown. We generated ADAM10 conditional knockout (ADAM10 cKO) mice lacking the ADAM10 gene primarily in OPCs by crossing NG2-Cre mice with ADAM10 loxp/loxp mice. We found that OPCs expressed ADAM10 in the mouse corpus callosum and the hippocampus. ADAM10 cKO mice showed significant loss of back hair and reduction in weight and length on postnatal (30 ± 2.1) day, died at (65 ± 5) days after birth, and exhibited the “anxiety and depression-like” performances. Conditional knockout of ADAM10 in OPCs resulted in a prominent increase in myelination and a decrease in the number of OPCs in the corpus callosum at P30 owing to premyelination and lack of proliferation of OPCs. Moreover, the number of proliferating OPCs and mature oligodendrocytes (OLs) also decreased with age in the corpus callosum of ADAM10 cKO mice from P30 to P60. Western blot and RT-PCR results showed that the activation of Notch-1 and its four target genes, Hes1, Hes5, Hey1, and Hey2, was inhibited in the corpus callosum tissue of ADAM10 knockout mice. In our study, we provided experimental evidence to demonstrate that ADAM10 is essential for modulating CNS myelination and OPC development by activating Notch-1 signaling in the developing and adult mouse brain.

A disintegrin and metalloproteinase 10 (ADAM10) plays an essential role in the regulation of survival, proliferation, migration, and differentiation of various neural cells. Nevertheless, the role of ADAM10 in oligodendrocyte precursors (OPCs) and myelination in the central nervous system (CNS) of developing and adult mouse brains is still unknown. We generated ADAM10 conditional knockout (ADAM10 cKO) mice lacking the ADAM10 gene primarily in OPCs by crossing NG2-Cre mice with ADAM10 loxp/loxp mice. We found that OPCs expressed ADAM10 in the mouse corpus callosum and the hippocampus. ADAM10 cKO mice showed significant loss of back hair and reduction in weight and length on postnatal (30 ± 2.1) day, died at (65 ± 5) days after birth and exhibited the “anxiety and depression-like” performances. Conditional knockout of ADAM10 in OPCs resulted in a prominent increase in myelination and a decrease in the number of OPCs in the corpus callosum at P30 owing to premyelination and lack of proliferation of OPCs. Moreover, the number of proliferating OPCs and mature oligodendrocytes (OLs) also decreased with age in the corpus callosum of ADAM10 cKO mice from P30 to P60. Western blot and RT-PCR results showed that the activation of Notch-1 and its four target genes, Hes1, Hes5, Hey1, and Hey2, was inhibited in the corpus callosum tissue of ADAM10 knockout mice. In our study, we provided experimental evidence to demonstrate that ADAM10 is essential for modulating CNS myelination and OPC development by activating Notch-1 signalling in the developing and adult mouse brain.

Objective Carbon monoxide (CO) poisoning is one of the common causes of poisoning in patients and can result in significant neurological sequelae. However, few studies have focused on the elderly population. Method We retrospectively reviewed elderly (age≥60 years) with CO poisoning from non-fire accidents and non-suicid at at the 6th medical center PLA general hospital in China from 2013 to 2023. We analyzed the patients’ epidemiological characteristics and outcome; identified the risk factors for patients who developed delayed neurological sequelae (DNS) and long-term neurological sequelae (LNS); compared the data of patients who received hyperbaric oxygen (HBO) to those who received normobaric oxygen (NBO) therapy. Result A total of 167 elderly patients were enrolled. The annual case number decreased from 2013 to 2023, particularly during the cold months (November to February). The most common source of exposure was coal heating (89.8%). The most common presenting symptoms were consciousness changes (86.8%). Eighty-eight patients (52.3%) developed DNS, of which sixty-nine patients (78.4%) converted to LNS. The most common imaging manifestations were hypoxic ischemic damage in the basal ganglia (54.3%) and demyelination in white matter (45.7%). After multivariate analysis, initial GCS score and coma time were the independent risk factor for patients with DNS (p＜0.001). Interestingly, myocardial injury was more common in non DNS elderly patients than in DNS patients (p＜0.001); only coma time was an independent risk factor for patients with LNS (p＜0.001). There was no significant difference between HBO (p=0.196) and NBO (p=0.379) in the occurrence of DNS and LNS in elderly patients with CO poisoning. Conclusion: Only initial GCS score and coma time are the risk factors of DNS for elderly patients, and coma time alone is a high-risk factor for poor prognosis of CO poisoning in the elderly. Moreover, HBO is not superior to NBO in elderly patients with CO poisoning. Special attention should be given and follow-up should be performed to elderly patients, particularly those have longer coma time and CO exposure time, and lower initial GCS score in acute CO poisoning.