RESUMEN
Cerebral vasospasm is determined as a temporary narrowing of cerebral arteries a few days after an aneurysmal subarachnoid hemorrhage. The onset of this vascular event usually evolves with new neurological deficits or progression of ischemic areas. The success of interventions to treat or revert this condition is not satisfying. In addition to cerebral vasospasm, early brain injury plays an important role as a contributor to subarachnoid hemorrhage's mortality. In this sense, stellate ganglion block appears as an alternative to reduce sympathetic system's activation, one of the main pathophysiological mechanisms involved in brain injury. Over the past few years, there is growing evidence that stellate ganglion block can contribute to decline patient morbidity from subarachnoid hemorrhage. Is it time to include this procedure as a standard treatment after aneurysm rupture?
RESUMEN
The accumulation of cross-ß-sheet amyloid fibrils is a hallmark of all human amyloid diseases. The compound epigallocatechin-3-gallate (EGCG), the main polyphenol present in green tea, has been described to have beneficial effects in several pathologies, including amyloidogenic diseases. This polyphenol blocks amyloidogenesis and disaggregates a broad range of amyloidogenic peptides comprising amyloid fibrils in vitro. The mechanism by which EGCG acts in the context of amyloid aggregation is not clear. Most of the biological effects of EGCG are attributable to its antioxidant activity. However, EGCG-oxidized products appear to be sufficient for the majority of EGCG amyloid remodeling observed against some polypeptides. If controlled, EGCG oxidation can afford homogenous microparticles (MPs) and can serve as drug delivery agents. Herein, we produced EGCG MPs by oxidative coupling and analyzed their activity during the aggregation of the protein α-synuclein (α-syn), the main protein related to Parkinson's disease. The MPs modestly remodeled mature amyloid fibrils and efficiently inhibited the amyloidogenic aggregation of α-syn. The MPs showed low cytotoxicity against both dopaminergic cells and microglial cells. The MPs reduced the cytotoxic effects of α-syn oligomers. Interestingly, the MPs were loaded with another antiamyloidogenic compound, increasing their activity against amyloid aggregation. We propose the use of EGCG MPs as a bifunctional strategy, blocking amyloid aggregation directly and carrying a molecule that can act synergistically to alleviate the symptoms caused by the amyloidogenic pathway.