Fucoidan from Fucus vesiculosus Fails to Improve Outcomes Following Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is the most fatal stroke subtype, with no effective therapies. Hematoma expansion and inflammation play major roles in the pathophysiology of ICH, contributing to primary and secondary brain injury, respectively. Fucoidan, a polysaccharide from the brown seaweed Fucus vesiculosus, has been reported to activate a platelet receptor that may function in limiting bleeding, and to exhibit anti-inflammatory effects. As such, the aim of the present study was to examine the effects of fucoidan on hemorrhaging and neurological outcomes after ICH. Male CD-1 mice were subjected to experimental ICH by infusion of bacterial collagenase. Animals were randomly divided into the following groups: sham, ICH + vehicle, ICH + 25 mg/kg fucoidan, ICH + 75 mg/kg fucoidan, and ICH + 100 mg/kg fucoidan. Brain water content, neurobehavioral outcomes, and hemoglobin content were evaluated at 24 h post ICH. Our findings show that fucoidan failed to attenuate the ICH-induced increase in BWC. The neurological deficits that result from ICH also did not differ in the treatment groups at all three doses. Finally, we found that fucoidan had no effect on the hemoglobin content after ICH. We postulate that fucoidan treatment did not improve the measured outcomes after ICH because we used crude fucoidan, which has a high molecular weight, in our study. High-molecular-weight fucoidans are reported to have less therapeutic potential than low molecular weight fucoidans. They have been shown to exhibit anti-coagulant and pro-apoptotic properties, which seem to outweigh their anti-inflammatory and potential procoagulant abilities. We propose that using a low-molecular-weight fucoidan, or fractionating the crude polysaccharide, may be effective in treating ICH. Future studies are needed to confirm this.

Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Edema formation, inflammation and increased blood-brain barrier permeability contribute to poor outcomes after intracerebral hemorrhage (ICH). This study examined the therapeutic effect of dimethyl fumarate (DMF), a fumaric acid ester that activates nuclear factor erythroid-2 related factor 2 (Nrf2) and Nrf2 heterodimerization effector protein musculo-aponeurotic fibrosarcoma-G (MAFG) in a murine ICH model. METHODS: Male CD-1 mice (n=176) were subjected to intrastriatal infusion of bacterial collagenase (n=126), autologous blood (n=18) or sham surgery (n=32). Four (4) animals not subjected to ICH (naive) were also included in the study. After ICH, animals either received vehicle, dimethyl fumarate (10 mg or 100 mg/kg) or casein kinase 2 inhibitor (E)-3-(2,3,4,5-tetrabromophenyl)acrylic acid (TBCA). Thirty-two mice also received scrambled siRNA or MAFG siRNA 24h before ICH. Brain water content and neurological function were evaluated. RESULTS: Dimethyl fumarate reduced Evans blue dye extravasation, decreased brain water content, and improved neurological deficits at 24 and 72 h after ICH. Casein kinase 2 inhibitor TBCA and MAFG siRNA prevented the effect of dimethyl fumarate on brain edema and neurological function. After ICH, ICAM-1 levels increased and casein kinase 2 levels decreased. Dimethyl fumarate reduced ICAM-1 but enhanced casein kinase 2 levels. Again, casein kinase 2 inhibitor TBCA and MAFG siRNA abolished the effect of dimethyl fumarate on ICAM-1 and casein kinase 2. Dimethyl fumarate preserved pNrf2 and MAFG expression in the nuclear lysate after ICH and the effect of dimethyl fumarate was abolished by casein kinase 2 inhibitor TBCA and MAFG siRNA. Dimethyl fumarate reduced microglia activation in peri-hematoma areas after ICH. The protective effect of dimethyl fumarate on brain edema and neurological function was also observed in a blood injection mouse model. CONCLUSION: Dimethyl fumarate ameliorated inflammation, reduced blood-brain barrier permeability, and improved neurological outcomes by casein kinase 2 and Nrf2 signaling pathways after experimental ICH in mice.

Neurobehavioural evaluation of Lophira alata (Ochnaceae) stem bark extract in mice.

BACKGROUND: Stem bark and leaves of Lophira alata (Family: Ochnaceae) have been used traditionally for their anti-psychotic, anti-convulsant and anxiolytic properties. Since no existing data was found on the neurobehavioural properties, this study was carried out to evaluate some neurobehavioural properties of the aqueous extract of the stem bark of L. alata in animal models. METHODS: The oral mean lethal dose (LD50) of the extract was estimated, and preliminary phytochemical screening was conducted. Lophira alata extract (200, 400 and 800 mg/kg, p.o.) was investigated for antidepressant effect using the forced swim and tail suspension tests, and the anxiolytic potential was assessed using the stair case and hole board tests. Pentylenetetrazole-induced convulsion test was used to investigate the anticonvulsant potential of the extract. RESULTS: The LD50 was estimated to be >5000 mg/kg. Oral administration of L. alata extract produced a significant (p<0.05) non-dose-dependent decrease in the period of immobility in both the forced swim and tail suspension tests. While a significant decrease (p<0.05) in episodes of grooming was recorded in the staircase test, the number of head dips was not significantly reduced (p>0.05) in the hole board test. In the pentylenetetrazole-induced convulsion, a non-dose-dependent increase in onset of tonic-clonic seizures and protection from death was recorded. CONCLUSIONS: The results obtained suggest that the aqueous stem bark extract of L. alata possesses neurobehavioural properties which may account for its use in ethnomedicine.