Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size after focal ischemia in rats

I don't think our doctors are going to agree to stopping blood flow several times after the clot is removed. But it is a fascinating idea.  I'll have to add reperfusion injury as another problem in the neuronal cascade of death.
http://www.nature.com/jcbfm/journal/v26/n9/full/9600348a.html

Heng Zhao^1,2, Robert M Sapolsky^1,2,3 and Gary K Steinberg^1,2

1. ¹Department of Neurosurgery, Stanford University, Stanford, California, USA
2. ²Department of Stanford Stroke Center, Stanford University, Stanford, California, USA
3. ³Department of Biological Sciences, Stanford University, Stanford, California, USA

Correspondence: Dr H Zhao, Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Rd, Rm P306, MSLS Bld, Stanford, California 94305-5327, USA. E-mail: hzhao@stanford.edu

Received 24 March 2006; Revised 25 April 2006; Accepted 3 May 2006; Published online 31 May 2006.

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Abstract

Cerebral ischemic preconditioning protects against stroke, but is clinically feasible only when the occurrence of stroke is predictable. Reperfusion plays a critical role in cerebral injury after stroke; we tested the hypothesis that interrupting reperfusion lessens ischemic injury. We found for the first time that such postconditioning with a series of mechanical interruptions of reperfusion significantly reduces ischemic damage. Focal ischemia was generated by permanent distal middle cerebral artery (MCA) occlusion plus transient bilateral common carotid artery (CCA) occlusion. After 30 secs of CCA reperfusion, ischemic postconditioning was performed by occluding CCAs for 10 secs, and then allowing for another two cycles of 30 secs of reperfusion and 10 secs of CCA occlusion. Infarct size was measured 2 days later. Cerebral blood flow (CBF) was measured in animals subjected to permanent MCA occlusion plus 15 mins of bilateral CCA occlusion, which demonstrates that postconditioning disturbed the early hyperemia immediately after reperfusion. Postconditioning dose dependently reduced infarct size in animals subjected to permanent MCA occlusion combined with 15, 30, and 60 mins of bilateral CCA occlusion, by reducing infarct size approximately 80%, 51%, and 17%, respectively. In addition, postconditioning blocked terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling-positive staining, a marker of apoptosis, in the penumbra 2 days after stroke. Furthermore, in situ superoxide detection using hydroethidine suggested that postconditioning attenuated superoxide products during early reperfusion after stroke. In conclusion, postconditioning reduced infarct size, most plausibly by blocking apoptosis and free radical generation. With further study it may eventually be clinically applicable for stroke treatment.