Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult.
The effect of gamma irradiation (0.5 and 1.0 kGy) and/or cooking on the proximate composition, mineral content, tannin content, phytic acid content and the in vitro protein digestibility (IVPD) of two Sudanese faba bean cultivars (BB7-S1 and SH-S2) was investigated in the present study. The results obtained revealed that gamma irradiation and/or cooking treatments have slight effect in chemical composition and mineral content, while they caused significant (P ≤ 0.05) reduction on tannin content for both cultivars. Cooking of faba bean seeds also insignificantly (P ≤ 0.05) reduced phytic acid content for both cultivars, while irradiation process and/or cooking had fluctuated effect. For both cultivars, irradiation of seeds and/or cooking increased the in vitro protein digestibility (IVPD), with maximum value of IVPD (79.97%) obtained for cultivar BB7-S1. The results indicate that the treatments used in this study might improve the nutritive quality of faba bean seed due to reduction in antinutritional factors with a concomitant increase in IVPD.
CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia.
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