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Updated: Aug 15, 2026
Focal Cerebral Ischemia Model by Endovascular Suture Occlusion of the Middle Cerebral Artery in the Rat
Published on: February 5, 2011
Experimental treatment for focal hyperglycemic ischemic brain injury in the rat
Nasim Farrokhnia1, Magnus W Roos, Andreas Terént
1Department of Medical Sciences, Stroke Unit, Uppsala University Hospital, Sweden. nasim.farrokhnia@medsci.uu.se
Abstract:
Hyperglycemia aggravates ischemic brain injury, possibly due to the activation of signaling pathways involving reactive oxygen species, Src and mitogen-activated protein kinases. The aim of this study was to investigate the effects of the spin trap agent alpha-phenyl-N-tert-butyl nitrone (PBN), the Src family kinase inhibitor PP2 and the MEK1-inhibitor U0126 on focal hyperglycemic ischemic brain injury. Temporary middle cerebral artery occlusion (90 min) was induced in four groups of rats (PBN, PP2, and U0126 vs. control). Neurological testing and tetrazolium red staining were performed after 1 day. PBN decreased the infarct volume by 70% compared with the control (P<0.05) and a tendency towards reduced infarcts was seen in the PP2 or U0126 groups. Furthermore, neurological testing was consistent with the volumetric analysis. In conclusion, PBN appears to be a potential neuroprotective agent in hyperglycemic, focal ischemic brain injury, while the efficacy of PP2 and U0126 could not be confirmed by the present data.
Insights
Alpha-phenyl-N-tert-butyl nitrone (PBN) significantly reduced hyperglycemic ischemic brain injury in rats. Other tested agents showed limited efficacy, suggesting PBN
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Hyperglycemia exacerbates ischemic brain injury.
- This exacerbation may involve reactive oxygen species (ROS), Src kinases, and mitogen-activated protein kinases (MAPKs).
Purpose of the Study:
- To investigate the neuroprotective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a Src inhibitor (PP2), and a MEK1 inhibitor (U0126) in a rat model of focal hyperglycemic ischemic brain injury.
Main Methods:
- Focal cerebral artery occlusion was induced in rats for 90 minutes.
- Four groups were studied: control, PBN, PP2, and U0126.
- Neurological function and infarct volume (tetrazolium red staining) were assessed after 24 hours.
Main Results:
- PBN treatment reduced infarct volume by 70% compared to controls (P<0.05).
- PP2 and U0126 groups showed a trend towards reduced infarcts, but results were not statistically significant.
- Neurological testing results correlated with infarct volume measurements.
Conclusions:
- Alpha-phenyl-N-tert-butyl nitrone (PBN) demonstrates significant neuroprotective potential against hyperglycemic focal ischemic brain injury.
- The efficacy of Src kinase inhibition (PP2) and MEK1 inhibition (U0126) was not confirmed in this study.
