Abstract | BACKGROUND: METHODS: SAH model was built by endovascular filament perforation method in adult male C57BL/6J mice, and then, insulin was administrated via intranasal route at 0, 24, and 48 h post-SAH. EBI was assessed according to the neurological performance, BBB damage, brain edema, neuroinflammatory reaction, and neuronal apoptosis at each time point. To evaluate metabolic conditions, microdialysis was used to continuously monitor the real-time levels of glucose, pyruvate, and lactate in interstitial fluid (ISF) in living animals. The mRNA and protein expression of glucose transporter-1 and 3 (GLUT-1 and -3) were also tested by RT-PCR and Western blot in brain after SAH. RESULTS: Compared to vehicle, intranasal insulin treatment promoted the relative mRNA and protein levels of GLUT-1 in SAH brain (0.98 ± 0.020 vs 0.33 ± 0.016 at 24 h, 0.91 ± 0.25 vs 0.21 ± 0.013 at 48 h and 0.94 ± 0.025 vs 0.28 ± 0.015 at 72 h in mRNA/0.96 ± 0.023 vs 0.36 ± 0.015 at 24 h, 0.91 ± 0.022 vs 0.22 ± 0.011 at 48 h and 0.95 ± 0.024 vs 0.27 ± 0.014 at 72 h in protein, n = 8/Group, p < 0.001). Similar results were also observed in GLUT-3. Intranasal insulin reduced the lactate/ pyruvate ratio (LPR) and increased ISF glucose level. It also improved neurological dysfunction, BBB damage, and brain edema and attenuated the levels of pro-inflammatory cytokines as well as neuronal apoptosis after SAH. CONCLUSIONS: The intranasal insulin treatment protects brain from EBI possibly via improving metabolic distress after SAH.
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Authors | Long-Biao Xu, Hua-Dong Huang, Ming Zhao, Guo-Chong Zhu, Zhen Xu |
Journal | Neurocritical care
(Neurocrit Care)
Vol. 34
Issue 1
Pg. 154-166
(02 2021)
ISSN: 1556-0961 [Electronic] United States |
PMID | 32495315
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Insulin
- Neuroprotective Agents
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Topics |
- Administration, Intranasal
- Animals
- Apoptosis
- Blood-Brain Barrier
- Brain Edema
(drug therapy, etiology)
- Brain Injuries
(drug therapy)
- Insulin
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Neuroprotective Agents
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Subarachnoid Hemorrhage
(complications, drug therapy)
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