ABSTRACT
Post-stroke neurological deficits and mortality are often associated with vascular disruption and neuronal apoptosis. Galectin-3 (Gal3) is a potent pro-survival and angiogenic factor. However, little is known about its protective role in the cerebral ischemia/reperfusion (I/R) injury. We have previously shown significant up-regulation of Gal3 in the post-stroke rat brain, and that blocking of Gal3 with neutralizing antibody decreases the cerebral blood vessel density. Our current study demonstrates that intracerebral local delivery of the Gal3 into rat brain at the time of reperfusion exerts neuroprotection. Ischemic lesion volume and neuronal cell death were significantly reduced as compared with the vehicle-treated MCAO rat brains. Gal3 increased vessel density and neuronal survival after I/R in rat brains. Importantly, Gal3-treated groups showed significant improvement in motor and sensory functional recovery. Gal3 increased neuronal cell viability under in vitro oxygen-glucose deprivation conditions in association with increased phosphorylated-Akt, decreased phosphorylated-ERK1/2, and reduced caspase-3 activity. Gene expression analysis showed down regulation of pro-apoptotic and inflammatory genes including Fas-ligand, and upregulation of pro-survival and pro-angiogenic genes including Bcl-2, PECAM, and occludin. These results indicate a key role for Gal3 in neuro-vascular protection and functional recovery following ischemic stroke through modulation of angiogenic and apoptotic pathways.
Subject(s)
Angiogenesis Inducing Agents/pharmacology , Apoptosis/drug effects , Caspases/drug effects , Galectin 3/therapeutic use , Ischemic Stroke/prevention & control , Neuroprotective Agents/pharmacology , Proto-Oncogene Proteins c-akt/drug effects , Signal Transduction/drug effects , Animals , Brain , Cell Death/drug effects , Galectin 3/administration & dosage , Gene Expression/drug effects , Hypoxia, Brain/drug therapy , Microinjections , Neurons/drug effects , Neurons/pathology , Rats , Rats, Inbred SHR , Reperfusion Injury/prevention & controlABSTRACT
Technicians in a commercial laboratory manually uncap up to 700 sample tubes daily in preparation for bioanalytical testing. Manually twisting off sample tube caps not only is a time-consuming task, but also poses increased risk for muscle fatigue and repetitive-motion injuries. An automated device capable of uncapping sample tubes at a rate faster than the current workflow would be valuable for minimizing strain on technicians' hands and saving time. Although several commercial sample tube-uncapping products exist, they are not always usable for a workload that uses a mix of tube sizes and specific workflow. A functioning uncapping device was developed that can semi-automatically uncap sample tubes with three different heights and diameters and was compatible with the workflow in a commercial laboratory setting. Under limited testing, the average success rate with uncapping each of the three sample tube sizes or a mix of them was 90% or more, more than three times faster than manual uncapping, and met standard acceptance criteria using mass spectrometry. Our device with its current performance is still a prototype, requiring further development. It showed promise for ergonomic benefit to the laboratory technicians, however, reducing the necessity to manually unscrew caps.