TY - JOUR
T1 - Hypoxic stress visualized in the cervical spinal cord of ALS patients
AU - Yamashita, Toru
AU - Hatakeyama, Tetsuhiro
AU - Sato, Kota
AU - Fukui, Yusuke
AU - Hishikawa, Nozomi
AU - Takemoto, Mami
AU - Ohta, Yasuyuki
AU - Nishiyama, Yoshihiro
AU - Kawai, Nobuyuki
AU - Tamiya, Takashi
AU - Abe, Koji
N1 - Funding Information:
This work was partly supported by a Grant-in-Aid for Scientific Research (B) 17H0419611, (C) 17H0975609, and 17K1082709 and by Grants-in-Aid from the Research Committees (Kaji R, Toba K, and Tsuji S) from the Japan Agency for Medical Research and Development 7211700121, 7211800049 and 7211800130.
Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Objective: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Hypoxic stress is suspected as the pathogenesis of ALS, however, no positron emission tomography (PET) study for hypoxic stress has been conducted in the spinal cord of ALS patients. Methods: In the present study, we examined cervical spinal hypoxic stress of nineALS patients with upper extremity (U/E) atrophy by18F-fluoromisonidazole (FMISO) PET. Results: On the ipsilateral side of C1 and C5 levels, 18F-FMISO uptake increased significantly compared with the contralateral side (*p < 0.05) and the control subject (**p < 0.01). In addition, a strong correlation was found between 18F-FMISO uptake of the C5 level and the rate of progression of the ALS FRS-R score (R = 0.781, *p = 0.013). Conclusion: These results indicate that hypoxic stress increased in the spinal cord of ALS patients with a close link to ALS progression. Both hypoxic stress and a compromised response to hypoxia, which may lead to subsequent motor neuron death, could be a potential therapeutic target for ALS.
AB - Objective: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Hypoxic stress is suspected as the pathogenesis of ALS, however, no positron emission tomography (PET) study for hypoxic stress has been conducted in the spinal cord of ALS patients. Methods: In the present study, we examined cervical spinal hypoxic stress of nineALS patients with upper extremity (U/E) atrophy by18F-fluoromisonidazole (FMISO) PET. Results: On the ipsilateral side of C1 and C5 levels, 18F-FMISO uptake increased significantly compared with the contralateral side (*p < 0.05) and the control subject (**p < 0.01). In addition, a strong correlation was found between 18F-FMISO uptake of the C5 level and the rate of progression of the ALS FRS-R score (R = 0.781, *p = 0.013). Conclusion: These results indicate that hypoxic stress increased in the spinal cord of ALS patients with a close link to ALS progression. Both hypoxic stress and a compromised response to hypoxia, which may lead to subsequent motor neuron death, could be a potential therapeutic target for ALS.
KW - ALS
KW - PET
KW - cervical spinal cord
KW - f-FMISO
KW - hypoxic stress
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U2 - 10.1080/01616412.2020.1866383
DO - 10.1080/01616412.2020.1866383
M3 - Article
C2 - 33377424
AN - SCOPUS:85098546110
VL - 43
SP - 429
EP - 433
JO - Neurological Research
JF - Neurological Research
SN - 0161-6412
IS - 6
ER -