Ischemic post-conditioning is neuroprotective even at delayed tPA administration after embolic stroke in female rats

Document Type : Original Article

Authors

1 Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

2 Department of Nursing, School of Nursing and Midwifery, Jiroft University of Medical Sciences, Jiroft, Iran

3 Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

4 Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract

Objective(s): Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats. 
Materials and Methods: Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated.
Results: This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (P<0.05). The combination of PC and tPA reduced the infarct volume, brain edema, and protected BBB. tPA+PC could alleviate neurobehavioral disorders compared with control or tPA. Moreover, PC had the capability of MMP-9 reduction when combined with delayed tPA (P<0.05).
Conclusion: Conduction of PC not only alleviated some stroke complications but also enhanced the therapeutic time window of tPA in female rats under embolic stroke. 

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 12
December 2021
Pages 1676-1682

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