Nanoliposome containing cyclosporine A reduced neuroinflammation responses and improved neurological activities in cerebral ischemia/reperfusion in rat

Cyclosporine A (CsA) is known as a neuroprotective agent against cerebral ischemia/reperfusion (I/R) in animal models. However, the significant therapeutic effects of CsA have been observed in high systemic doses or manipulating the blood–brain barrier, resulting in systemic side effects and toxicit...

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Bibliographic Details
Published in:	Fundamental & clinical pharmacology Vol. 31; no. 2; pp. 185 - 193
Main Authors:	Partoazar, Alireza, Nasoohi, Sanaz, Rezayat, Sayed M., Gilani, Kambiz, Mehr, Shahram E., Amani, Amir, Rahimi, Nastaran, Dehpour, Ahmad R.
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-04-2017
Subjects:	Animal models Animals Blood-brain barrier Brain injury Brain Ischemia - prevention & control Cerebral blood flow Cyclosporine - administration & dosage Cyclosporine - pharmacology cyclosporine A Cyclosporins Disease Models, Animal Edema Free form Head injuries Infarction, Middle Cerebral Artery Inflammation Inflammation - prevention & control Intravenous administration Ischemia Liposomes Male nanoliposome Nanoparticles Neuroprotection Neuroprotective Agents - administration & dosage Neuroprotective Agents - pharmacology Occlusion Peroxidase - metabolism Pharmacology Proteins Rats Rats, Wistar Reperfusion Reperfusion Injury - drug therapy Reperfusion Injury - pathology Side effects Stroke Stroke - prevention & control Time Factors Toxicity Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α nanoliposome cyclosporine A inflammation stroke
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Summary:	Cyclosporine A (CsA) is known as a neuroprotective agent against cerebral ischemia/reperfusion (I/R) in animal models. However, the significant therapeutic effects of CsA have been observed in high systemic doses or manipulating the blood–brain barrier, resulting in systemic side effects and toxicity. As the liposome nanocarriers have been developed for efficient delivery of peptide and proteins, liposomal CsA (Lipo‐CsA) could improve cerebral (I/R) injuries. In this study, the liposomal CsA formulation (CsA at dose of 2.5 mg/kg) was prepared to assess the brain injury outcomes in 90 min middle cerebral artery occlusion (MCAO) stroke model followed by 48 h reperfusion in treating rats. Five minutes after induction of cerebral ischemia in rats, intravenous (iv) administration of Lipo‐CsA significantly (P < 0.001) recovered the infarct size, the brain edema, and the neurological activities compared to corresponding control groups following 48 h I/R. In addition, after 48 h cerebral I/R, Lipo‐CsA potentially (P < 0.001) inhibited the inflammation responses including MPO activity and tumor necrosis factor‐alpha level in comparison to other groups. In conclusion, the results indicate that the low dose of CsA in liposomal formulation is more effective compared to higher dose of free form of CsA in treatment of ischemic brain in rats.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0767-3981 1472-8206
DOI:	10.1111/fcp.12244