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Int J Med Sci 2020; 17(17):2622-2634. doi:10.7150/ijms.47560 This issue Cite

Research Paper

Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia

Chien-Ming Chao1,2, Chun-Liang Chen3, Ko-Chi Niu4, Cheng-Hsien Lin5, Ling-Yu Tang6, Lieh-Sheng Lin7✉, Ching-Ping Chang6✉

1. Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
2. Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan.
3. Department of Gastroenterology and General Surgery, Chi Mei Medical Hospital, Chiali, Tainan, Taiwan.
4. Department of Hyperbaric Oxygen, Chi Mei Medical Center, Tainan, Taiwan.
5. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
6. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
7. Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan.

✉ Corresponding author: Lieh-Sheng Lin M.D., D.M.S. Department of Neurosurgery, Taipei Medical University Hospital Mailing address: No. 250 Wu-Hsing Street, Taipei City 110, Taiwan; Phone: +886-2- 22490088; E-mail: liehshengcom. Ching-Ping Chan More

Citation:
Chao CM, Chen CL, Niu KC, Lin CH, Tang LY, Lin LS, Chang CP. Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia. Int J Med Sci 2020; 17(17):2622-2634. doi:10.7150/ijms.47560. https://www.medsci.org/v17p2622.htm
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Abstract

Background: Hypoxia-inducible factor-1α (HIF-1α), heat shock protein-72 (HSP-72), hemeoxygenase-1 (HO-1), and matrix metalloproteinase-9 (MMP-9) have been identified as potential therapeutic targets in the brain for cerebral ischemia. To elucidate their underlying mechanisms, we first aimed to ascertain whether these proteins participate in the pathogenesis of heat-induced ischemic damage to the hypothalamus of rats. Second, we investigated whether hypobaric hypoxia preconditioning (HHP) attenuates heat-induced hypothalamic ischemic/hypoxic injury by modulating these proteins in situ.

Methods: Anesthetized rats treated with or without HHP were subjected to heat stress. Hypothalamic ischemic/hypoxic damage was evaluated by measuring hypothalamic levels of cerebral blood flow (CBF), partial oxygen pressure (PO2), and hypothalamic temperature via an implanted probe. Hypothalamic apoptotic neurons were counted by measuring the number of NeuN/caspase-3/DAPI triple-stained cells. Hypothalamic protein expression of HIF-1α, HSP-72, HO-1, and MMP-9 was determined biochemically.

Results: Before the start of the thermal experiments, rats were subjected to 5 hours of HHP (0.66 ATA or 18.3% O2) daily for 5 consecutive days per week for 2 weeks, which led to significant loss of body weight, reduced brown adipose tissue (BAT) wet weight and decreased body temperature. The animals were then subjected to thermal studies. Twenty minutes after heat stress, heat-exposed rats not treated with HHP displayed significantly higher core and hypothalamic temperatures, hypothalamic MMP-9 levels, and numbers of hypothalamic apoptotic neurons but significantly lower mean blood pressure, hypothalamic blood flow, and PO2 values than control rats not exposed to heat. In heat-exposed rats, HHP significantly increased the hypothalamic levels of HIF-1α, HSP-72, and HO-1 but significantly alleviated body and hypothalamic hyperthermia, hypotension, hypothalamic ischemia, hypoxia, neuronal apoptosis and degeneration.

Conclusions: HHP may protect against hypothalamic ischemic/hypoxic injury and overexpression of MMP-9 by upregulating the hypothalamic expression of HIF-1α, HSP-72, and HO-1 in rats subjected to heatstroke.

Keywords: hypothalamus, ischemic/hypoxic injury, heatstroke, hypobaric hypoxia

Citation styles

APA
Chao, C.M., Chen, C.L., Niu, K.C., Lin, C.H., Tang, L.Y., Lin, L.S., Chang, C.P. (2020). Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia. International Journal of Medical Sciences, 17(17), 2622-2634. https://doi.org/10.7150/ijms.47560.

ACS
Chao, C.M.; Chen, C.L.; Niu, K.C.; Lin, C.H.; Tang, L.Y.; Lin, L.S.; Chang, C.P. Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia. Int. J. Med. Sci. 2020, 17 (17), 2622-2634. DOI: 10.7150/ijms.47560.

NLM
Chao CM, Chen CL, Niu KC, Lin CH, Tang LY, Lin LS, Chang CP. Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia. Int J Med Sci 2020; 17(17):2622-2634. doi:10.7150/ijms.47560. https://www.medsci.org/v17p2622.htm

CSE
Chao CM, Chen CL, Niu KC, Lin CH, Tang LY, Lin LS, Chang CP. 2020. Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia. Int J Med Sci. 17(17):2622-2634.

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