Intraarterial administration of norcantharidin attenuates ischemic stroke damage in rodents when given at the time of reperfusion: novel uses of endovascular capabilities
| Autor: | BethAnn McLaughlin, Robert J. Singer, Moneeb Ehtesham, Daniel C. Colvin, Mitchell Odom, Imad Saeed Khan, C. Chad Quarles |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Matrix Metalloproteinase Inhibitors Neuroprotection Article Brain Ischemia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Text mining Spontaneously hypertensive rat Animals Medicine Stroke Norcantharidin business.industry General Medicine Bridged Bicyclo Compounds Heterocyclic medicine.disease Rats Disease Models Animal Injections Intra-Arterial Matrix Metalloproteinase 9 chemistry 030220 oncology & carcinogenesis Anesthesia Ischemic stroke Systemic administration Immunohistochemistry business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurosurgery. 125:152-159 |
| ISSN: | 1933-0693 0022-3085 |
| DOI: | 10.3171/2015.4.jns142400 |
| Popis: | OBJECT Matrix metalloprotease-9 (MMP-9) plays a critical role in infarct progression, blood-brain barrier (BBB) disruption, and vasogenic edema. While systemic administration of MMP-9 inhibitors has shown neuroprotective promise in ischemic stroke, there has been little effort to incorporate these drugs into endovascular modalities. By modifying the rodent middle cerebral artery occlusion (MCAO) model to allow local intraarterial delivery of drugs, one has the ability to mimic endovascular delivery of therapeutics. Using this model, the authors sought to maximize the protective potential of MMP-9 inhibition by intraarterial administration of an MMP-9 inhibitor, norcantharidin (NCTD). METHODS Spontaneously hypertensive rats were subjected to 90-minute MCAO followed immediately by local intraarterial administration of NCTD. The rats’ neurobehavioral performances were scored according to the ladder rung walking test results and the Garcia neurological test for as long as 7 days after stroke. MRI was also conducted 24 hours after the stroke to assess infarct volume and BBB disruption. At the end of the experimental protocol, rat brains were used for active MMP-9 immunohistochemical analysis to assess the degree of MMP-9 inhibition. RESULTS NCTD-treated rats showed significantly better neurobehavioral scores for all days tested. MR images also depicted significantly decreased infarct volumes and BBB disruption 24 hours after stroke. Inhibition of MMP-9 expression in the ischemic region was depicted on immunohistochemical analysis, wherein treated rats showed decreased active MMP-9 staining compared with controls. CONCLUSIONS Intraarterial NCTD significantly improved outcome when administered at the time of reperfusion in a spontaneously hypertensive rat stroke model. This study suggests that supplementing endovascular revascularization with local neuroprotective drug therapy may be a viable therapeutic strategy. |
| Databáze: | OpenAIRE |
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