Disruption of the blood–brain barrier (BBB) accompanies many brain diseases, including stroke, neurodegenerative diseases, and brain tumors, leading to swelling, increased neuroinflammation, and neuronal death. In recent years, it has become clear that the c-Jun N-terminal kinase (JNK) signaling pathway is involved in disruption of the structural integrity of the BBB. Activation of the JNK signaling pathway has a negative effect on the functioning of the cellular elements of the neurovascular unit that form the BBB. The aim of this review is to assess the role of the JNK signaling pathway in the disruption of the structural integrity of the BBB in animal models of stroke (MCAO/R, middle cerebral artery occlusion with reperfusion), Alzheimer’s disease, and brain tumors and to analyze the effects of compounds of various natures that directly or indirectly affect the activity of the JNK signaling pathway. These compounds can reduce damage to the BBB and brain edema, reduce neuroinflammation and oxidative stress, reduce the expression of proapoptotic factors, and increase the expression of tight junction proteins. Certain compounds mitigate BBB dysfunction, being promising candidates for neuroprotective therapies. These agents exert their effects, in part, through inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway, a mechanism linked to reduced neuronal damage and improved BBB integrity.

Background: Systemic arterial pressure (AP) depends on two physiological variables: cardiac output (CO) and total peripheral resistance (TPR). The latter depends on vascular hindrance and blood viscosity (BV). However, the relative contributions of t

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.

Background: Postmenopausal women often develop hemorheological disorders which may affect the systemic blood circulation and present a cardiovascular risk factor. Postmenopausal women often develop hemorheological disorders which may affect the syste