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Updated: Sep 30, 2026
Selective and Permanent Occlusion of the Middle Cerebral Artery in Rats: An Experimental Approach for Studying Motor and Spatial Memory Deficits
Published on: March 20, 2026
MitoK(ATP) opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat
Katsuyoshi Shimizu1, Zsombor Lacza, Nishadi Rajapakse
1Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA. KATSUYOSHIS@aol.com
Abstract:
We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 microl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated with 2 mM diazoxide (13.8 +/- 0.7, n = 13) compared with sham treatment (9.5 +/- 0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral side) of sham treatment animals was 43.6 +/- 3.6% (n = 12). Treatment with 2 mM diazoxide reduced the infarct volume to 20.9 +/- 4.8% (n = 13, P < 0.05). Effects of diazoxide were prominent in the cerebral cortex. The protective effect of diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate (100 mM in 10 microl saline), a selective blocker of mitoK(ATP) channels (n = 6). These results indicate that selective opening of the mitoK(ATP) channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain.
Insights
Diazoxide, a mitochondrial ATP-sensitive K(+) channel opener, significantly reduced brain damage and infarct volume in rats after middle cerebral artery occlusion (MCAO). This neuroprotective effect highlights the therapeutic potential of targeting mitoK(ATP) channels in stroke.
Area of Science:
- Neuroscience
- Cardiovascular Medicine
- Pharmacology
Background:
- Middle cerebral artery occlusion (MCAO) is a common model for studying ischemic stroke.
- Ischemic stroke leads to significant brain damage and neurological deficits.
- Mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels are potential therapeutic targets for neuroprotection.
Purpose of the Study:
- To investigate the neuroprotective effects of diazoxide, a selective opener of mitoK(ATP) channels, against MCAO-induced brain injury in rats.
- To determine if the protective effects of diazoxide are mediated through mitoK(ATP) channels.
Main Methods:
- Male Wistar rats underwent MCAO surgery.
- Diazoxide or saline was administered intracerebroventricularly 15 minutes before MCAO.
- Neurological scores and infarct volumes were assessed 24 hours after MCAO.
- The role of mitoK(ATP) channels was evaluated using 5-hydroxydecanoate, a specific blocker.
Main Results:
- Treatment with 2 mM diazoxide significantly improved neurological scores compared to sham treatment (13.8 vs. 9.5).
- Diazoxide (2 mM) reduced the total infarct volume by approximately 50% (20.9% vs. 43.6%).
- The neuroprotective effect of diazoxide was abolished by pretreatment with 5-hydroxydecanoate, confirming the involvement of mitoK(ATP) channels.
Conclusions:
- Selective opening of mitoK(ATP) channels by diazoxide confers significant neuroprotection against ischemia-reperfusion injury in the rat brain.
- Diazoxide demonstrates therapeutic potential for treating stroke by protecting brain tissue from ischemic damage.
- Targeting mitoK(ATP) channels represents a promising strategy for developing novel stroke therapies.
