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Ultrasound-Mediated Kallidinogenase-Loaded Microbubble Targeted Therapy for Acute Cerebral Infarction
- Source :
- Journal of Stroke and Cerebrovascular Diseases. 27:686-696
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Background The neuroprotective effects of kallidinogenase against acute cerebral infarction have been demonstrated, and the use of microbubbles has been suggested as a therapeutic mechanism for drug delivery. This study was designed to investigate the optimal parameters for preparing kallidinogenase-loaded microbubbles (KLMs) and to evaluate the effects of KLM-targeted therapy on neurogenesis and angiogenesis following experimental acute cerebral infarction in rats. Materials and Methods KLMs were prepared by mechanical shaking. Male Wistar rats were randomly divided into an ultrasound-mediated KLM-treated group and 4 control groups. Treatments were administered via daily tail vein injection on 6 consecutive days, starting at 24 hours after middle cerebral artery occlusion (MCAO). The ultrasound-treated groups were subjected to a 2-MHz pulse of ultrasonic irradiation on the lateral skull of the ischemic side for 10 minutes during injection. Cell proliferation was examined using a 5-bromo-2-deoxyuridine assay. Infarct volume and neurological function were evaluated on days 3 and 7 after MCAO. Results The ultrasound-mediated KLM and kallidinogenase treatments significantly increased the numbers of doublecortin-immunoreactive cells in the subventricular zone (SVZ) and laminin+ cells in the peri-infarction region on day 7 after MCAO, compared with the other 3 groups (all P Conclusions Treatment with the ultrasound-mediated KLMs promoted the proliferation of SVZ neuroblasts and vascular regeneration, which contributed to functional improvement after stroke. These findings provide a novel therapy for ischemic stroke.
- Subjects :
- Male
medicine.medical_specialty
Doublecortin Protein
Time Factors
Angiogenesis
Neurogenesis
Ultrasonic Therapy
Sulfur Hexafluoride
Urology
Contrast Media
Neovascularization, Physiologic
Subventricular zone
030204 cardiovascular system & hematology
Neuroprotection
03 medical and health sciences
0302 clinical medicine
Neural Stem Cells
medicine
Animals
Rats, Wistar
Stroke
Phospholipids
Cell Proliferation
Microbubbles
Behavior, Animal
Cerebral infarction
business.industry
Rehabilitation
Brain
Infarction, Middle Cerebral Artery
medicine.disease
Neural stem cell
Disease Models, Animal
Neuroprotective Agents
medicine.anatomical_structure
Anesthesia
Injections, Intravenous
Kallikreins
Surgery
Neurology (clinical)
Cardiology and Cardiovascular Medicine
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10523057
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Stroke and Cerebrovascular Diseases
- Accession number :
- edsair.doi.dedup.....f347a393bdac5e2f6cc2e69ba737f136