DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion

Abstract

A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.

Machine learning based analysis of stroke lesions on mouse tissue sections

“…Smartphone acquisition brings shadows (d, at white background) and its low resolution at 72 dpi brings relative inaccuracies. SA can surprisingly detect strokes even in images acquired online from previously published manuscripts 23,24 (e and f); here resolution is again the only determining factor: the low resolution of 72 dpi in (e) provides moderate accuracy compared to the 300 dpi in (f).…”

“…For the evaluation of StrokeAnalyst on variable image-acquisition modalities and resolution, TTC-slices of Exp3 were additionally scanned at 600, 1200 and 2400 dpi over a white or black background or captured at 72 dpi with the camera of a commercial smartphone. Retrieved images of TTC-stained slices from previously published manuscripts (online, from their pdf) in white 23 and black background 24 were also used. All these images had to be converted to a standard 1200 dpi resolution prior to analysis with StrokeAnalyst, done with any image-processing software, e.g.…”

“…We tested the functionality of StrokeAnalyst on images scanned at different resolutions (600, 1200 and 2400 dpi) and backgrounds (white and black), on images from published manuscripts, 23,24 and images captured by a mobile-phone camera at a low resolution of 72 dpi. In all cases, as shown representatively in Figure 4, StrokeAnalyst successfully detected the ischemic lesion, even in TTC-slices with poor color differentiation (slice on black background in Figure 4(a) to (c)).…”

Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke

“…In our other study [ 59 ], it was shown that the administration of DSIP and its analog KND-peptide during occlusion led to the death of animals, and when administered during the reperfusion, a decrease in the size of the brain and heart infarction was observed. Presumably, mortality could be a consequence of the inactivation of the genes for the early response of c-Fos upon administration of DSIP during occlusion, whose activity is associated with the activation of NMDA receptors [ 60 , 61 ].…”