curcumin and Cerebral-Hemorrhage

Topics: Apoptosis; Brain Edema; Brain Injuries; Cerebral Hemorrhage; Curcumin; Humans; Janus Kinase 1; Neuroinflammatory Diseases; Neurons; STAT1 Transcription Factor

Intracerebral hemorrhage (ICH) is a form of severe stroke, the pathology of which is tied closely to a recently discovered form of programmed cell death known as ferroptosis. Curcumin (Cur) is a common phenolic compound extracted from the rhizome of. In this study, we encapsulated Cur in NPs (Cur-NPs) and explored the effect of these Cur-NPs to enhance Cur delivery both in vitro and in vivo. Furthermore, we evaluated the anti-ferroptosis effect of Cur-NPs in ICH model mice and erastin-treated HT22 murine hippocampal cells.. The resultant Cur-NPs were spherical and exhibited a particle size of 127.31±2.73 nm, a PDI of 0.21±0.01 and a zeta potential of -0.25±0.02 mV. When applied to Madin Darby canine kidney (MDCK) cells in vitro, these Cur-NPs were nonspecifically internalized via multiple endocytic pathways, with plasma membrane microcapsules and clathrin-mediated uptake being the dominant mechanisms. Within cells, these NPs accumulated in lysosomes, endoplasmic reticulum and mitochondria. Cur-NPs were capable of passing through physiological barriers in a zebrafish model system. When administrated to C57BL/6 mice, they significantly improved Cur delivery to the brain. Most notably, when administered to ICH model mice, Cur-NPs achieved superior therapeutic outcomes relative to other treatments. In a final series of experiments, these Cur-NPs were shown to suppress erastin-induced ferroptosis in HT22 murine hippocampal cells.. These Cur-NPs represent a promising means of improving Cur delivery to the brain and thereby better treating ICH.

Topics: Animals; Cerebral Hemorrhage; Curcumin; Dogs; Drug Delivery Systems; Ferroptosis; Mice; Mice, Inbred C57BL; Nanoparticles; Particle Size; Zebrafish

Prolonged hydrocephalus is a major cause of severe disability and death of intraventricular hemorrhage (IVH) patients. However, the therapeutic options to minimize the detrimental effects of post-hemorrhagic hydrocephalus are limited. Curcumin has been reported to confer neuroprotective effects in numerous neurological diseases and injuries, but its role in IVH-induced hydrocephalus has not been determined. The aim of present study was to determine whether curcumin treatment ameliorates blood brain barrier (BBB) damage and reduces the incidence of post-hemorrhagic hydrocephalus in IVH rat model. Autologous blood intraventricular injection was used to establish the IVH model. Our results revealed that repeated intraperitoneal injection of curcumin ameliorated IVH-induced learning and memory deficits as determined by Morris water maze and reduced the incidence of post-hemorrhagic hydrocephalus in a dose-dependent manner at 28 d post-IVH induction. Further, the increased BBB permeability and brain edema induced by IVH were significantly reduced by curcumin administration. In summary, these findings highlighted the important role of curcumin in improving neurological function deficits and protecting against BBB disruption via promoting the neurovascular unit restoration, and thus it reduced the severity of post-hemorrhagic hydrocephalus in the long term. It is believed that curcumin might prove to be an effective therapeutic component in prevent the post-IVH hydrocephalus in the near future.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Cerebral Hemorrhage; Cerebral Ventricles; Curcumin; Disease Models, Animal; Humans; Hydrocephalus; Injections, Intraventricular; Male; Neuroprotective Agents; Rats, Sprague-Dawley

T lymphocytes contribute to inflammation, thereby exacerbating neuronal injury after cerebral ischemia. An increasing amount of evidence indicates that inflammation is a key contributor to intracerebral hemorrhage (ICH)-induced secondary brain injury. Curcumin, a low-molecular-weight curry spice that is derived from the Curcuma longa plant, suppresses T lymphocyte proliferation and migration. Based on these findings, we investigated whether treatment with curcumin would reduce the number of cerebral T lymphocytes in mice with experimentally induced ICH. We found that a large number of T lymphocytes infiltrated the brain at 3days post-ICH. Curcumin significantly improved neurological scores and reduced brain edema in mice with ICH, consistent with a role in reducing neuroinflammation and neurovascular injury. Using flow cytometry, we observed significantly fewer T lymphocytes in brain samples obtained from the curcumin-treated group than in samples obtained from the vehicle-treated group. Moreover, Western blot analysis and immunostaining indicated that treatment with curcumin significantly reduced the expression of a vascular cell adhesion molecule-1 (VCAM-1), interferon-γ (INF-γ) and interleukin-17 (IL-17) in the mouse brain at 72h post-ICH. Our results suggest that administering curcumin may alleviate cerebral inflammation resulting from ICH, at least in part by reducing the infiltration of T lymphocytes into the brain. Therefore, preventing T lymphocytes from infiltrating the brain may become a new strategy for treating clinical ICH.

Topics: Animals; Brain; Brain Edema; Cerebral Hemorrhage; Curcumin; Encephalitis; Interferon-gamma; Interleukin-17; Male; Mice, Inbred C57BL; T-Lymphocytes; Vascular Cell Adhesion Molecule-1

Much evidence demonstrates that microglia mediated neuroinflammation is an important contributor to the inflammatory injury in intracerebral hemorrhage (ICH). Therefore, the compounds that can inhibit neuroinflammation are greatly needed. In the current study, we examined whether curcumin, present in a Chinese medicinal plant, could prevent ICH induced microglia activation and confer protection against neurotoxicity. The cytokines of microglia were measured by ELISA, p38MAPK/PKC and NF-κB were measured by Western blot and EMSA. Microglial toxicity was assessed using MTT and FACS assays. And neurological function was evaluated by animal behavioristics. We found that curcumin prevented ICH-induced inflammatory molecules through NF-κB activation via the p38MAPK/PKC pathway in vitro. In addition, curcumin protected hippocampal HT22 cells from indirect toxicity mediated by ICH-treated microglia cells. Further, curcumin also attenuated ICH-induced neurological deficit and cerebral water content in vivo. Together, our findings suggest that curcumin could suppress ICH induced inflammatory injury and represent a novel herbal sources for ICH therapeutical strategy.

Topics: Animals; Apoptosis; Cell Line; Cell Movement; Cerebral Hemorrhage; Curcumin; Cytokines; Disease Models, Animal; Hippocampus; Inflammation; Inflammation Mediators; Male; Mice; Microglia; Neuroprotective Agents; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Protein Kinase C; Signal Transduction

Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; but neurosurgical clot evacuation may not be feasible in all patients and treatment options remain largely supportive. Thus, novel therapeutic approaches to promote hematoma resolution are needed. In the present study, the authors investigated whether the curry spice curcumin limited neurovascular injury following ICH in mice.. Intracerebral hemorrhage was induced in adult male CD-1 mice by intracerebral administration of collagenase or autologous blood. Clinically relevant doses of curcumin (75-300 mg/kg) were administered up to 6 hours after ICH, and hematoma volume, inflammatory gene expression, blood-brain barrier permeability, and brain edema were assessed over the first 72 hours. Neurological assessments were performed to correlate neurovascular protection with functional outcomes.. Curcumin increased hematoma resolution at 72 hours post-ICH. This effect was associated with a significant reduction in the expression of the proinflammatory mediators, tumor necrosis factor-α, interleukin-6, and interleukin-1β. Curcumin also reduced disruption of the blood-brain barrier and attenuated the formation of vasogenic edema following ICH. Consistent with the reduction in neuroinflammation and neurovascular injury, curcumin significantly improved neurological outcome scores after ICH.. Curcumin promoted hematoma resolution and limited neurological injury following ICH. These data may indicate clinical utility for curcumin as an adjunct therapy to reduce brain injury and improve patient outcome.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Cerebral Hemorrhage; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Hematoma; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred Strains; Treatment Outcome; Tumor Necrosis Factor-alpha

Previous studies revealed that curcumin is neuroprotective in diseases of the central nervous system such as cerebral ischemia and traumatic brain injury. However, the effect of curcumin on intracerebral hemorrhage remains unclear. We, therefore, investigated the pre-clinical effect of curcumin treatment on neurological outcomes following intracerebral hemorrhage, using a mouse model. Intracerebral hemorrhage was induced by autologous blood injection into the right basal ganglia. Curcumin (150 mg/kg) was administered 15 min after intracerebral hemorrhage. Grid walk and neurological scores were evaluated at 1, 3, 7, and 14 days post-injury. Mice were killed at 24 h or 28 days following injury, for histological examination. Evans Blue and water content in the ipsilateral and contralateral hemispheres were measured to evaluate the extent of blood-brain barrier disruption and brain edema. Zonula occludens-1 was detected by immunostaining. In situ zymography was used to measure the localization and focal enzymatic activity of matrix metalloproteinase. Our results demonstrated that curcumin reduced brain edema, measured by alleviated water content and Evans Blue leakage at 24 h (p<0.05). Lateral ventricle measurements indicated that curcumin reduced brain tissue loss in the ipsilateral hemisphere (p<0.05). The same dose of curcumin also significantly attenuated neurological deficits at 1 and 3 days of intracerebral hemorrhage (p<0.05). Immunostaining showed that tight junction continuity around the hematoma was better sustained in curcumin-treated mice than in vehicle-treated mice. At 24 h, the number of matrix metalloproteinase-positive cells was significantly reduced by curcumin (p<0.05). Our study suggests that curcumin ameliorates intracerebral hemorrhage damage by preventing matrix metalloproteinase-mediated blood-brain barrier damage and brain edema, which might provide therapeutic potential for intracerebral hemorrhage.

Topics: Animals; Blood-Brain Barrier; Cerebral Hemorrhage; Curcumin; Disease Models, Animal; Injections, Intraperitoneal; Male; Mice; Neuroprotective Agents; Psychomotor Performance; Recovery of Function