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Daptomycin recovers stroke injury and advances blood-brain barrier in rat brain

Background: Daptomycin (DPM) an antibiotic of lipopeptide class has been used in the treatment of infections caused by gram-positive bacteria. DPM interferes with Matrix Metalloproteinases (MMPs) activity the enzyme responsible for brain damage. However effects of DPM in early treatments of brain injury followed by repurfusion are not well studied. The aim of current research was to evaluate the consequences of DPM administration in early stage of stroke followed by perfusion in rats induced to stroke, and effects on Blood Brain Barrier (BBB) and neuro-inflammation were studied. The study was guided by MRI studies, evaluation of histology and biochemical parameters.

Methods: For present study 30 adult rats spontaneously hypertensive were subjected to 90 minutes of transient Middle Cerebral Artery Occlusion (MCAO). In very early stage the rats received repurfusion and also one group of rats were administered a unit dose of DPM (50 mg/kg) and the other group only received vehicle. The rats were studied at defined time points for upto 4 weeks with MRI.

Results: MRI studies showed DPM reduced infract size and also prevented brain tissue damages compared to vehicle treated rats in ischemic zones after two and four weeks of stroke. Arterial Spin Labeling (ASL) showed DPM improved Cerebral Blood Flow (CBF) and perfusion. Results of dynamic contrast-enhanced MRI demonstrated that DPM decreased permeability of BBB which was associated with elevated levels of TJPs when assessed with Western blot. Mediators of inflammation were examined by Immunohistochemistry. The findings suggested DPM reduced the inflammatory reaction by modulating inflammatory mediators (IL 1β, IL 6, IL 10 and TNF α) and NF κB (p65) due to ischemic injury.

Conclusions: DPM treatment at very early stage of stroke followed by reperfusion significantly encouraged neurovascular remodeling and attenuated stroke injury by decreasing brain tissue loss, advancing blood brain barrier and reducing overall inflammatory response.

Author(s): Chunshui Yang, Jianqing Pan, Chuanming Wang, Wenfei Li, Lijie Ren