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Updated: Jun 2, 2026
A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion
Published on: May 31, 2024
Brain distribution and elimination of recombinant human TIMP-1 after cerebral ischemia and reperfusion in rats
Yalian Sa1, Jinsong Hao, Divya Samineni
1Department of Neurology, College of Medicine, University of Cincinnati, OH 45267-0532, USA.
Objective:
To investigate recombinant human TIMP-1 ((125)I-rhTIMP-1) half-life in blood and its distribution in rat brain tissue after cerebral ischemia/reperfusion as part of a therapeutic development paradigm.
Method:
A suture model of the middle cerebral artery occlusion was used. (125)I-labeled rhTIMP-1 at 60 microg/kg (11.23 microCi/microg) was administered to rats intravenously at the beginning of reperfusion. Blood and brain tissue were collected. The radioactivity was detected with a gamma counter and analyzed by autoradiography.
Results:
The blood half-life T(1/2) of (125)I-rhTIMP-1 was 42.2 hours. Thirty minutes after (125)I-rhTIMP-1 administration, an increased accumulation of (125)I-rhTIMP-1 in the ischemic hemisphere was observed. The maximum brain tissue concentration C(max) was 26.1 ng/g at 1.5 hours in the striatum and 13.9 ng/g at 5 hours in the cortex when the uptake percentage of brain tissue to blood was 6.1±0.4 and 6.7±2.1%, respectively. The cortex and striatum elimination half-lives T(1/2) were 45.3 and 39.2 hours, respectively. Electrophoretic analysis of ischemic samples for (125)I-rhTIMP-1 showed a clear 28 kDa band 1.5 hours after (125)I-rhTIMP-1 administration in the cortex and striatum. The intensity of the 28 kDa band decreased after 3.0 hours of the administration. Some (125)I-rhTIMP-1 maintained its molecular integrity for 8.5 hours in ischemic striatum after reperfusion.
Discussion:
(125)I-labeled rhTIMP-1 was distributed quickly into ischemic brain tissue and had a slow elimination in both blood and brain tissue. These results, along with other studies suggesting therapeutic benefits, will aid in the development of TIMP-1 for protecting ischemic stroke.
