Fucoidan protects CA1 pyramidal neurons of the hippocampus and preserves the cognitive profile of rats subjected to transient forebrain ischemia.

Fucoidan, a polysaccharide derived from brown seaweeds, especially Fucus Vesiculosus has been documented as an effective neuroprotectant. This study investigates the efficacy of fucoidan in mitigating the cognitive deficits in the rat model of vascular dementia induced through the 4-vessel occlusions (4VO) method. Male Wistar rats weighing about 250-300 g were randomly assigned into four groups, sham, lesion (4VO), 4VO + F5mg/kg, and 4VO + F50mg/kg. The rats were assessed for cognitive behaviour performance through novel object task, T-maze and Morris water maze, and finally, the hippocampus from the brain was harvested to quantify the profile of CA1 pyramidal neurons through CFV staining and the expression of inflammatory markers and angiogenic markers were quantified through western blot assessment on day7 and 30 of the study period. The rats were treated with fucoidan at a dose of 50 mg/kg. body weight showed improved spatial learning and memory compared to the lesion group and the cytoarchitecture of CA1 pyramidal cells was observed to be well preserved. The expression of IL1ß, IL6, TNFα, NFk-B, CD68 and HIFα were found to be down-regulated, while on the contrary the VEGFR2 and angiopoietin-1 were up regulated in the 4VO + F50mg/kg group when compared with the lesion group. In conclusion, this study ascertains the role of fucoidan in support of the cognitive profile of rats subjected to vascular dementia and in preserving the CA1 pyramidal neurons of the hippocampus by regulating the inflammatory and angiogenic factors.

Fucoidan (A Sulfated Polysaccharide) and Cerebroprotein in Combination Alleviate the Neuroinflammation-mediated Neural Damage and Functional Deficits in the Focal Cerebral Ischemia Model of Rat.

Cerebral ischemic reperfusion injury could emanate a cascade of events ensuing in neural death and severe neurobehavioural deficits. The currently available interventions have failed to target the multimodal, interlinked mechanisms that operate cerebral ischemia-induced damage and functional loss. So an integrative intervention has become a mandate to overcome the deleterious mechanisms involved in cerebral ischemic pathophysiology. In this study, adult male Sprague dawley rats were exposed to 2 hours of right middle cerebral artery occlusion (rMCAo) followed by reperfusion, and the intervention group received Fucoidan alone at a dose of 50 mg/kg, i.p (intraperitoneal), Cerebrolysin alone at a dose of 2.5 mg/kg body weight and the combination of both. The sham rats were exposed to surgical procedures, except for the rMCAo. The assessments of the groups were made 24 h after the rMCAo. The stand-alone treatment with Fucoidan, Cerebrolysin has shown a better outcome in the neurobehavioral and, histopathological assessments and the combination has made a significant reduction in the neurological deficits and the infarct volume when compared to the standalone groups. The BBB integrity was well preserved in the combination group when compared with the lesion and standalone groups. Moreover, the combined intervention reduced the level of pro-inflammatory cytokines TNFα, NFkB, IL1α, IL1-ß, IL-6, CD68, COX-2, and mRNA expression of inflammatory genes IL1α, IL1-ß, IL-6, IBA-1, and COX-2 effectively. In conclusion, the present study suggests that rMCAo induced neuroinflammation and neurobehavioural alterations were attenuated by intervention with a combination of Fucoidan and cerebrolysin; Further, Fucoidan and Cerebrolysin combination improved the ischemic tolerance level by promoting the proteins and genes that regulate the inflammatory cytokines and in aiding better recovery after ischemic reperfusion injury.

Glycyrrhizic acid renders robust neuroprotection in rodent model of vascular dementia by controlling oxidative stress and curtailing cytochrome-c release.

Background: Chronic cerebral hypoperfusion (CCH), a concern for neurocognitive health, is linked to various vascular ailments and other comorbidities. This study primarily aims to explain the mitigating effects of glycyrrhizic acid (GA) on cognitive health challenged by chronic cerebral hypoperfusion. Methods: Adult male Sprague Dawley rats were allocated into four groups: (i) Sham, (ii) Lesion (2VO), (iii) GA treated (20 mg/kg), and (iv) lithium chloride (Li) treated (40 mg/kg). On 30th postoperative day the rats were tested for cognitive behaviour through a repertoire of tests. Rats were transcardially perfused and the brain samples were obtained for histological assessments. For biochemical assessments, hippocampus isolated from fresh brain was utilized. Results: The antioxidant propensity of GA curtailed ROS generation by restoring mitochondrial complex I and IV, enzymatic and non-enzymatic antioxidant activity. However, Li group exhibited significantly reduced antioxidant defence, when compared with GA. The strong antioxidant defence had caused considerable restoration of pyramidal neurons, myelin and dendritic spine density in GA treated than Li treated. GA treated rats showed a remarkable amelioration of cognitive deficits when compared with lesion rats. Finally, GA also reduced the cytochrome-c release, thus creating a blockade for further succession of apoptotic events. Conclusion: The outcome of this study clearly implies that GA shows promising neuroprotection in CCH-induced rats by enhancing the endogenous antioxidants and curtails the apoptosis by reducing cytochrome-c release. GA was also found to be much better than Li through modulation of GSK3ß/Nrf2 pathway, in turn, mitigates the adverse consequences of CCH.