iridoids and Brain-Edema

Oxidative stress and neurocyte apoptosis are crucial pathophysiological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Geniposide (GNP) has been reported to exert neuroprotective effects by reducing oxidative injury and neurocyte apoptosis. However, the effect of GNP has not been clarified in EBI after SAH. The study was performed to evaluate the neuroprotective effects and mechanisms of GNP in EBI after SAH.. A total of 60 male Wistar rats were randomly divided into five groups. The prechiasmatic cistern SAH model was used in this study. SAH grade was evaluated using a grading system. Neurological function was evaluated using the Garcia scores. Brain edema was measured by the wet-dry method. Blood-brain barrier (BBB) permeability was measured by the extravasation of Evans Blue (EB). The neurocyte apoptosis was observed using TUNEL assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and quinone oxidoreductase-1 (NQO-1) were performed. The results showed that GNP reduced brain edema, attenuated BBB permeability, inhibited neurocyte apoptosis and improved neurological function. Moreover, GNP also decreased the levels of ROS and MDA, elevated Nrf2 expression in the temporal cortex and up-regulated the expression of NQO-1, HO-1 and GST after SAH.. GNP could ameliorate oxidative stress and neurocyte apoptosis to exert neuroprotective effects by Nrf2 pathway.

Topics: Animals; Apoptosis; Brain; Brain Edema; Brain Injuries; Glutathione Transferase; Iridoids; Male; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Rats, Wistar; Subarachnoid Hemorrhage

We aimed to investigate whether geniposide, a main component extracted from Gardenia jasminoides Ellis fruit, could exert neuroprotective functions against traumatic brain injury (TBI). Enzyme-linked immunosorbent assay (ELISA) was used for detection of plasma cytokines. Real-time polymerase chain reaction (RT-PCR) was employed for measurements of mRNA levels of cytokines. Neurological outcomes were evaluated by modified neurological severity score (mNSS) and Rota-Rod. Blood-brain barrier (BBB) integrity and brain edema were assessed. Protein expression was tested by Western blot. The plasma levels of interleukin (IL)-1β, IL-6, IL-8 and IL-10 were all elevated in patients with TBI compared to those of healthy controls. TBI rats treated with geniposide showed lower mNSS and longer fall latency time than untreated TBI rats. BBB integrity was maintained and brain edema was reduced by geniposide treatment in TBI rats. Plasma levels of IL-1β, IL-6 and IL-8 were significantly repressed by geniposide treatment in TBI rats, whereas IL-10 level was upregulated. mRNA expression levels of these cytokines in the brain tissues of TBI rats exhibited the same trends of changes. By testing p38 mitogen-activated protein kinase and NF-κB p65 activities, it was observed that phosphorylated (p)-p38 and p-p65 were dramatically inhibited by geniposide. In conclusion, geniposide exerts neuroprotective functions against TBI by inhibiting p-p38 and p-p65.

Topics: Adolescent; Adult; Animals; Anti-Inflammatory Agents; Blood-Brain Barrier; Brain Edema; Brain Injuries, Traumatic; Cytokines; Female; Humans; Imidazoles; Iridoids; Male; Middle Aged; Mitogen-Activated Protein Kinases; NF-kappa B; Phosphorylation; Pyrimidines; Rats, Sprague-Dawley; RNA, Messenger; Treatment Outcome; Young Adult

Intracerebral haemorrhage (ICH) as a devastating form of stroke has remained a public health threat due to lack of FDA-approved therapy. Oxidative stress originated from blood cell degradation products plays a crucial role in the ICH pathogenesis. In this study we evaluated oleuropein, a potent natural antioxidant from olive, in a well-established rat ICH model from overall symptoms to detailed molecular mechanism.. ICH model was established by collagenase injection to the brain of rats, which were randomly divided into groups with vehicle mock treatment, followed by treatment with different doses of oleuropein via daily intraperitoneal injection post-ICH for 3days. The overall neurological deficit, brain edema level and blood-brain barrier (BBB) integrity were then measured in different treatment groups. To understand the protection mechanism of oleuropein in ICH, BBB structural components ZO-1 and occludin, oxidative stress and MAPK signalling pathways were also examined.. Oleuropein treatment showed overall alleviation of ICH-associated neurological deficit and brain edema in a dose dependent manner. Consistently, it could preserve the BBB structure and attenuate oxidative stress as well as ICH-induced MAPK activation in brain tissue.. Our study suggests oleuropein could be used as a promising therapeutic agent for ICH.

Topics: Animals; Antioxidants; Blood-Brain Barrier; Brain Edema; Cerebral Hemorrhage; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Iridoid Glucosides; Iridoids; Male; MAP Kinase Signaling System; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stroke