curcumin and Subarachnoid-Hemorrhage

Objective To investigate the inhibitory effect of curcumin on early brain injury following subarachnoid hemorrhage (SAH) by inhibiting JNK/ c-Jun signal pathway. Methods Sixty adult male SD rats were randomly divided into four groups: sham operation group (sham group), SAH group, SAH group treated with 100 mg/(kg.d) curcumin and SAH group treated with 200 mg/(kg.d) curcumin, with 15 rats in each group. Endovascular puncture was used to induce SAH model. Nissl staining was used to test whether neurons were broken. TUNEL staining was used to detect apoptosis. Immunohistochemistry was used to investigate the expression of caspase-3. Western blot analysis was used to detect the expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3. Results Nissl staining indicated the decrease of Nissl bodies in SAH group, but increase of Nissl bodies in SAH group treated with curcumin. TUNEL staining showed that there were more apoptotic neurons in SAH group compared with sham group, while apoptotic neurons decreased after the treatment with curcumin, more obviously in the group treated with 200 mg/(kg.d) curcumin. The expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3 were up-regulated in SAH group compared with sham group. However, the expressions of those proteins were down-regulated after the treatment with curcumin, especially by higher-dose curcumin treatment. Conclusion Curcumin might suppress early brain injury after SAH by inhibiting JNK/c-Jun signal pathway and neuron apoptosis.

Topics: Animals; Apoptosis; Brain Injuries; Caspase 3; Curcumin; Humans; Male; MAP Kinase Kinase 4; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage

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

Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

Topics: Animals; Blood-Brain Barrier; Curcumin; Dose-Response Relationship, Drug; Inflammation Mediators; Lactic Acid; Male; Mortality; Nanoparticles; Neuroprotective Agents; Oxidative Stress; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Random Allocation; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage

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

Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon.. We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery.. Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice.. We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice.

Topics: Animals; Biomarkers; Blood-Brain Barrier; Blotting, Western; Brain Edema; Curcumin; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Subarachnoid Hemorrhage; Treatment Outcome

Curcumin (CCM) is a natural polyphenolic compound in Curcuma longa that has been reported to exhibit neuroprotective effects. Subarachnoid hemorrhage (SAH) is a severe neurological disorder with an unsatisfactory prognosis. Oxyhemoglobin (OxyHb) plays an important role in mediating the neurological deficits following SAH. The present study, therefore, aimed to investigate the effect of CCM on primary cortical neurons exposed to OxyHb neurotoxicity. Cortical neurons were exposed to OxyHb at a concentration of 10 μM in the presence or absence of 5 μM (low dose) or 10 μM (high dose) CCM for 24 h. Morphological changes in the neurons were observed. Cell viability and lactate dehydrogenase (LDH) release were assayed to determine the extent of cell injury. Additionally, levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were measured. Neuronal apoptosis was assayed via TUNEL staining and protein levels of cleaved caspase-3, Bax, and Bcl-2 were measured by Western blot. Levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were measured using ELISA kits. Our results suggested that CCM at both low and high doses markedly improved cell viability and decreased LDH release. CCM treatment decreased neuronal apoptosis. Additionally, oxidative stress and inflammation induced by OxyHb were alleviated by CCM treatment. In conclusion, CCM inhibits neuronal apoptosis, and alleviates oxidative stress and inflammation in neurons subjected to OxyHb, suggesting that it may be beneficial in the treatment of brain damage following SAH.

Topics: Animals; Antioxidants; Apoptosis; Cell Survival; Cells, Cultured; Cerebral Cortex; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Lipid Peroxidation; Neuroimmunomodulation; Neurons; Neuroprotective Agents; Oxidative Stress; Oxyhemoglobins; Rats, Sprague-Dawley; Reactive Oxygen Species; Subarachnoid Hemorrhage

To investigate the effect of curcumin on learning and memory function of rats with subarachnoid hemorrhage (SAH) and the possible mechanism.. A total of 30 male Sprague-Dawley rats were randomly divided into three groups: Sham group, SAH group and curcumin (Cur) therapy group. Experimental SAH rat models were established by injecting autologous blood into the cisterna magna. Neurological deficits of rats were examined at different time points. Spatial learning and memory abilities were tested by Morris water maze test. The hippocampal tumor necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) were detected by ELISA. RESULTS Experimental SAH rat models were established successfully. Neurological scores of the SAH rats were significantly lower than those of the sham group. Curcumin therapy obviously improved the neurological deficits of rats compared with the SAH rats. Morris water maze test showed that SAH caused significant cognitive impairment with longer escape latency compared with the sham group. After treatment with curcumin for 4 weeks, the escape latency decreased significantly. The levels of TNF-α and iNOS in the curcumin-treated group were significantly lower than those of the SAH group.. SAH can cause learning and memory impairment in rats. Curcumin can recover learning and memory function through down-regulating hippocampal TNF-α and iNOS levels.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Hippocampus; Learning; Male; Memory; Nitric Oxide Synthase Type II; Random Allocation; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

More and more evidence revealed early brain injury (EBI) may determine the final outcome in aneurismal subarachnoid hemorrhage (SAH) patients. This study is of interest to examine the efficacy of nano-particle curcumin (nanocurcumin), a diarylheptanoid, on a SAH-induced EBI model.. A rodent double hemorrhage model was employed. Nanocurcumin (75/150/300μg/kg/day) was administered via osmotic mini-pump post-SAH. CSF samples were collected to examine IL-1β, IL-6, IL-8 and TNF-α (rt-PCR). Cerebral cortex was harvested for NF-κB (p50/p65) (western blot), caspases (rt-PCR) measurement.. Nanocurcumin significantly reduced the bio-expression of NF-κB (p65), when compared with the SAH groups. The levels of IL-1β and IL-6 were increased in animals subjected to SAH, compared with the healthy controls, but absent in the high dose nanocurcumin+SAH group. Moreover, the levels of TNF-α in the SAH groups were significantly elevated. Treatment with nanocurcumin (300μg/kg) reduced the level to the healthy control. The cleaved caspase-3 and -9a was significantly reduced in 300μg/kg nanocurcumin treatment groups (P<0.05).. Treatment with nanocurcumin exerts its neuroprotective effect through the upward regulation of NF-κB (p65) and also reduced mitochondrion related caspase-9a expression. Besides, nanocurcumin decreased CSF levels of TNF-α and IL-1β, which may contribute to the extrinsic antiapoptotic effect. This study shows promise to support curcuminin, in a nano-particle, could attenuate SAH induced EBI.

Topics: Analysis of Variance; Animals; Biocompatible Materials; Brain Injuries; Caspase 3; Caspase 9; Curcumin; Cytokines; Disease Models, Animal; Down-Regulation; Enzyme Inhibitors; Lactic Acid; Male; Neurologic Examination; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley; RNA, Messenger; Subarachnoid Hemorrhage; Transcription Factor RelA

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