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Updated: Jun 15, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats
Xian-kun Tu1, Wei-zhong Yang, Chun-hua Wang
1Department of Neurosurgery, Affiliated Union Hospital of Fujian Medical University, 29# Xinquan Road, Fuzhou, Fujian 350001, China.
Abstract:
5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-kappaB) p65 in rat brain was detected by immunohistochemistry and Western blot. Expression of inducible nitric oxide synthase (iNOS) in rat brain was determined by RT-PCR and Western blot. Nitric oxide production in rat brain was also measured 24 h after MCAO. The concentration of TNF-alpha and IL-1beta in serum were detected by ELISA. Zileuton significantly reduced neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-kappaB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-alpha and IL-1beta in serum. Our results suggest that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction.
Insights
Zileuton, a 5-lipoxygenase inhibitor, reduces brain damage and inflammation in rats experiencing ischemic stroke. This study explores its neuroprotective mechanisms by examining inflammatory markers and oxidative stress.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Previous studies indicated zileuton attenuates ischemic brain damage.
- The precise neuroprotective mechanisms of zileuton require further investigation.
Purpose of the Study:
- To investigate the underlying mechanisms of zileuton's neuroprotective effects in a rat model of permanent focal cerebral ischemia.
- To evaluate the impact of zileuton on neurological deficits, cerebral infarction, inflammatory responses, and oxidative stress.
Main Methods:
- Permanent middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats.
- Administration of zileuton or vehicle post-ischemia.
- Assessment of neurological deficit, infarct volume, myeloperoxidase (MPO) activity, lipid peroxidation (malondialdehyde), NF-kappaB p65, inducible nitric oxide synthase (iNOS) expression and activity, nitric oxide production, and serum TNF-alpha and IL-1beta levels.
Main Results:
- Zileuton significantly reduced neurological deficits, cerebral infarct volume, MPO activity, and lipid peroxidation.
- Zileuton inhibited NF-kappaB p65 expression and decreased iNOS expression and activity.
- Zileuton attenuated nitric oxide production and the release of TNF-alpha and IL-1beta.
Conclusions:
- Zileuton demonstrates neuroprotective effects in a rat model of permanent focal cerebral ischemia.
- The neuroprotection is associated with the inhibition of inflammatory reactions and oxidative stress.
