Abstract W P97: Post-ischemic Trans-arterial Regional Hypothermia Therapy Attenuates Microvascular Narrowing due to Astrocyte End-feet Swelling and Inhibits Subsequent Inflammatory Reactions in Ischemia Reperfusion Injury
Background and Purpose: We previously presented the robust neuroprotective effects of post-ischemic trans-arterial regional hypothermia therapy in I/R injury model rats (ISC 2014, San Diego). This treatment showed a significant suppression of infarct volume and inflammatory reaction at 24hrs after reperfusion. To characterize the neuroprotective effects in terms of microvascular integrity, we investigated microvascular morphological changes and inflammatory reactions by a time course analysis within 24hrs.
Methods: At reperfusion onset, 2hr-MCAO rats were divided into cold saline group (10°C, 20ml/kg of trans-arterial infusion from the recanalized artery for 15mins), warm saline group (37°C, in the same manner as cold saline group), and control group (recanalization only). Microvascular morphological changes were examined by vWF Immunohistochemistry (IHC) and transmission electron microscopy (TEM), and inflammatory reactions were examined by Western blotting and IHC at the time point of 0hr, 2hrs, 6hrs, and 24hrs of reperfusion.
Results: IHC analysis and TEM observation revealed that astrocyte end-feet swelling occurred at 2hrs and progressed to 6hrs, and microvascular narrowing due to the swelling occurred at 6hrs in control group. This microvascular morphological change was attenuated in cold saline group. While endothelial ICAM1 overexpression started at 6hrs in control group, MPO, MMP9, and Iba-1 overexpression occurred only at 24hrs in the same group. These inflammatory reactions were also inhibited in cold saline group.
Conclusions: Post-ischemic trans-arterial regional hypothermia therapy attenuated astrocyte end-feet swelling from 2hrs and the swelling induced microvascular narrowing at 6hrs. The treatment also inhibited endothelial ICAM-1 overexpression at 6hrs, and subsequently inhibited inflammatory reactions at 24hrs. The maintenance of microvascular morphological and functional integrity may be the primary cause of the neuroprotective effects by the regional hypothermia.
Author Disclosures: K. Kurisu: None. T. Abumiya: None. H. Nakamura: None. D. Shimbo: None. K. Kazumata: None. N. Nakayama: None. H. Shichinohe: None. M. Hokari: None. T. Osanai: None. H. Shimizu: None. K. Houkin: None.
- © 2015 by American Heart Association, Inc.