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Updated: Aug 24, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
FK506 abrogates delayed neuronal death via suppression of nitric oxide production in rats
Takahiro Sasaki1, Junichi Hamada, Mamoru Shibata
1Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. tsasaki@sc.itc.keio.ac.jp
Background And Purpose:
The mechanism of the neuroprotective effect of FK506 in relation to nitric oxide (NO) production has not been clarified in vivo. We have investigated the effect of FK506 on ischemia-induced NO production in association with the pathogenesis of delayed neuronal death (DND) in rats.
Methods:
In vivo microdialysis was performed in the hippocampus of male Sprague-Dawley rats (250-350 g). Dialysate samples were collected every 3 min. In the ischemia group (n=16), global ischemia was induced for 21 min and reperfusion was achieved. In the FK506 treatment group (n=25), FK506 (1 mg/kg, i.v.) was administered 21 min prior to the onset of global ischemia. Sham operations were done (n=15). The levels of NO(2)(-) in the dialysate samples were determined by the Griess reaction. The animals were decapitated 7 days after ischemia. Coronal brain sections were stained with hematoxylin and eosin.
Results:
In the ischemia group, the NO(2)(-) level significantly increased during ischemia. In the FK506 treatment group, there was no significant change in the NO(2)(-) level during ischemia. In histological examinations, FK506 treatment showed a neuroprotective effect against DND.
Conclusions:
The effect of FK506 inhibiting NO production contributes to the neuro-protective effect of FK506 on DND in the hippocampus.
Insights
FK506 inhibits nitric oxide (NO) production during ischemia, offering neuroprotection against delayed neuronal death (DND) in the hippocampus. This study clarifies FK506
Area of Science:
- Neuroscience
- Pharmacology
- Ischemic Stroke Research
Background:
- The neuroprotective mechanism of FK506 regarding nitric oxide (NO) production in vivo remains unclear.
- Investigating FK506's impact on ischemia-induced NO production is crucial for understanding delayed neuronal death (DND) pathogenesis.
Purpose of the Study:
- To investigate the effect of FK506 on ischemia-induced NO production.
- To determine the association between FK506, NO production, and DND in a rat model.
Main Methods:
- In vivo microdialysis in the rat hippocampus to measure NO2- levels.
- Global ischemia induced for 21 minutes with FK506 administered pre-ischemia.
- Histological analysis (hematoxylin and eosin staining) 7 days post-ischemia.
Main Results:
- Ischemia significantly increased NO2- levels in the hippocampus.
- FK506 treatment prevented the ischemia-induced increase in NO2- levels.
- FK506 demonstrated a significant neuroprotective effect against DND.
Conclusions:
- FK506's inhibition of NO production contributes to its neuroprotective effect against DND.
- Targeting NO production may be a therapeutic strategy for ischemic brain injury.
