curcumin and Vasospasm--Intracranial

Subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and early brain injury is a fatal clinical syndrome. Cerebral vasospasm and early brain injury are associated with inflammatory response and oxidative stress. Whether curcumin, which plays important roles to regulate inflammatory cytokines and inhibit oxidative stress, inhibits SAH-induced inflammation and oxidative stress are largely unknown.. Adult male rats underwent autologous blood injection into prechiasmatic cistern to induce SAH. Curcumin (150 mg/kg) was administered at 0.5, 24 and 48 hr post-SAH. Mortality calculation and neurological outcomes as well as morphological vasospasm of anterior cerebral artery were studied. Superoxide dismutase, lipid peroxidation, and inflammatory cytokines (MCP-1 and TNF-α) expression in prefrontal region were quantified. Furthermore, p65 and phosphor-p65 were quantitatively analyzed.. Curcumin remarkedly reduced mortality and ameliorated neurological deficits after SAH induction (. Curcumin can inhibit SAH-induced inflammatory response via restricting NF-κB activation to alleviate cerebral vasospasm and early brain injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Disease Models, Animal; Inflammation; Male; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage; Vasospasm, Intracranial

Cerebral vasospasm following subarachnoid hemorrhage (SAH) is the most important complication that effects the mortality and morbidity of patients with intracranial aneurysm. Today, the mechanisms of vasospasm are not understood in spite of experimental and clinical researches. The aim of our study was to investigate the effects of curcumin on vasospasm following SAH.. In this study, 64 rats (200-250 g weight) were divided into 7 groups. Group 1: having no treatment after SAH; Group 2: treatment with nimodipine after SAH; Group 3: treatment with nicorandil after SAH; Group 4: treatment with sildenafil citrate after SAH; Group 5: treatment with 150 mg/kg curcumin after SAH; Group 6: treatment with 300 mg/kg curcumin after SAH, Group 7: treatment with 600 mg/kg curcumin after SAH. The experimental SAH was induced by injection of autologous blood into the cisterna magna. After medical treatment, in the first hour, blood was taken for quantified the levels of TNF-α, IL-1β and IL-6. Then, cerebrum and cerebellum were removed for analysis. Basilar artery luminal diameter was measured and apoptotic cell count was performed with tissue samples.. Histopathological findings showed that, in sufficient dose, curcumin dilated the basilar artery beside anti-oxidant effect.. Curcumin can be used for the treatment of vasospasm as a new medical drug.

Topics: Animals; Apoptosis; Basilar Artery; Cerebellum; Cerebral Cortex; Curcumin; Interleukin-1beta; Interleukin-6; Male; Nicorandil; Nimodipine; Rats; Sildenafil Citrate; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha; Vasodilator Agents; Vasospasm, Intracranial

Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat.. A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed.. Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats.. Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Basilar Artery; Blotting, Western; Brain; Catalase; Curcumin; Dimethyl Sulfoxide; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; Glutamic Acid; Male; Malondialdehyde; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Sodium Chloride; Subarachnoid Hemorrhage; Superoxide Dismutase; Vasospasm, Intracranial

Cerebral vasospasm is a major cause of death and disability after subarachnoid hemorrhage (SAH); however, clinical therapies to limit the development of cerebral vasospasm are lacking. Although the causative factors underlying the development of cerebral vasospasm are poorly understood, oxidative stress contributes to disease progression. In the present study, curcumin (150 or 300 mg/kg) protected against the development of cerebral vasospasm and limited secondary cerebral infarction after SAH in mice. The protective effect of curcumin was associated with a significant attenuation of inflammatory gene expression and lipid peroxidation within the cerebral cortex and the middle cerebral artery. Despite the ability of curcumin to limit the development of cerebral vasospasm and secondary infarction, behavioral outcome was not improved, indicating a dissociation between cerebral vasospasm and neurologic outcome. Together, these data indicate a novel role for curcumin as a possible adjunct therapy after SAH, both to prevent the development of cerebral vasospasm and to reduce oxidative brain injury after secondary infarction.

Topics: Animals; Curcumin; Disease Models, Animal; Endothelium, Vascular; Inflammation; Lipid Peroxidation; Male; Mice; Mice, Inbred Strains; NF-kappa B; Subarachnoid Hemorrhage; Superoxides; Thiobarbituric Acid Reactive Substances; Vasospasm, Intracranial