An Overview of Stroke: Mechanism, In vivo Experimental Models Thereof, and Neuroprotective Agents

Khan, Mohd Muazzam; Badruddeen, .; Mujahid, Md.; Akhtar, Jamal

doi:10.2174/1389203721666200617133903

Cited by 3 publications

(1 citation statement)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…c -Jun N-terminal kinase (JNK) signaling is involved in the pathogenesis of ischemic stroke, along with multiple different signaling pathways [ 5 ]. The activation of JNK is observed after global and focal cerebral ischemia (FCI) in rats and mice [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], and various small-molecule JNK inhibitors have exhibited neuroprotective effects in animal models, including stroke [ 25 , 26 , 27 , 28 , 29 ]. Recently, we found that the specific JNK inhibitors IQ-1S and IQ-1L exhibited neuroprotective activity in mouse and rat models of FCI, and in a rat model of global cerebral ischemia [ 22 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Tryptanthrin-6-Oxime in a Rat Model of Transient Focal Cerebral Ischemia

Plotnikov,

Chernysheva,

Smol’yakova

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

The activation of c-Jun N-terminal kinase (JNK) plays an important role in stroke outcomes. Tryptanthrin-6-oxime (TRYP-Ox) is reported to have high affinity for JNK and anti-inflammatory activity and may be of interest as a promising neuroprotective agent. The aim of this study was to investigate the neuroprotective effects of TRYP-Ox in a rat model of transient focal cerebral ischemia (FCI), which involved intraluminal occlusion of the left middle cerebral artery (MCA) for 1 h. Animals in the experimental group were administered intraperitoneal injections of TRYP-Ox 30 min before reperfusion and 23 and 47 h after FCI. Neurological status was assessed 4, 24, and 48 h following FCI onset. Treatment with 5 and 10 mg/kg of TRYP-Ox decreased mean scores of neurological deficits by 35–49 and 46–67% at 24 and 48 h, respectively. At these doses, TRYP-Ox decreased the infarction size by 28–31% at 48 h after FCI. TRYP-Ox (10 mg/kg) reduced the content of interleukin (IL) 1β and tumor necrosis factor (TNF) in the ischemic core area of the MCA region by 33% and 38%, respectively, and attenuated cerebral edema by 11% in the left hemisphere, which was affected by infarction, and by 6% in the right, contralateral hemisphere 24 h after FCI. TRYP-Ox reduced c-Jun phosphorylation in the MCA pool at 1 h after reperfusion. TRYP-Ox was predicted to have high blood–brain barrier permeability using various calculated descriptors and binary classification trees. Indeed, reactive oxidant production was significantly lower in the brain homogenates from rats treated with TRYP-Ox versus that in control animals. Our data suggest that the neuroprotective activity of TRYP-Ox may be due to the ability of this compound to inhibit JNK and exhibit anti-inflammatory and antioxidant activity. Thus, TRYP-Ox may be considered a promising neuroprotective agent that potentially could be used for the development of new treatment strategies in cerebral ischemia.

show abstract