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Aims The aim of this work was to assess the effects of a probiotic diet on well-being of healthy seniors living in boarding and private homes in Marche Region, Italy. In particular, we focused on the modulation of high-sensitivity C-reactive protein (HsCRP), intestinal microbiota and short-chain fatty acids (SCFAs). Methods and Results Ninety-seven healthy seniors took part in a double-blind, placebo-controlled feeding study (59 fed probiotics, 38 fed placebo) for 6 months. Each volunteer ingested daily one food product or a dietary supplement enriched with Synbio® blend (Synbiotec Srl, Camerino, Italy) or the placebo (control group). Blood and faecal samples were collected before and at the end of the intervention period to perform biochemical and microbiological analyses. The serum HsCRP difference value after 6 months of treatment was significantly higher in the probiotic group than placebo (p < 0.05). After the intervention, a significant increase in faecal lactobacilli and a bifidobacteria increase in more participants were observed in the probiotic group. The 16S NGS analysis on the probiotic group showed a decreasing trend of Proteobacteria at the end of the treatment and conversely, an increasing trend of Actinobacteria and Verrucomicrobia phyla, to which the increase of Akkermansiaceae and Bifidobacteriaceae contributes at the family level. Finally, total short-chain fatty acids (SCFAs) and butyric acid were significantly higher in the probiotic group at the end of the treatment respect to the beginning. Conclusions Overall, this study emphasizes the beneficial anti-inflammageing effect of a prolonged diet based on functional foods enriched with Synbio® through the modulation of the intestinal microbiota and the consequent increase in the SCFA production. Significance and Impact of the Study Synbio® integration in elderly daily diet may be a preventive strategy to support healthy ageing.

Lipid peroxidation and the cytotoxic by-product 4-hydroxynonenal (4-HNE) have been implicated in neuronal perikaryal damage. This study sought to determine whether 4-HNE was involved in white matter damage in vivo and in vitro. Immunohistochemical studies detected an increase in cellular and axonal 4-HNE within the ischemic region in the rat after a 24-hour period of permanent middle cerebral artery occlusion. Exogenous 4-HNE (3.2 nmol) was stereotaxically injected into the subcortical white matter of rats that were killed 24 hours later. Damaged axons detected by accumulation of β-amyloid precursor protein (β-APP) were observed transversing medially and laterally away from the injection site after intracerebral injection of 4-HNE. In contrast, in the vehicle-treated animals, axonal damage was restricted to an area immediately surrounding the injection site. Exogenous 4-HNE produced oligodendrocyte cell death in culture in a time-dependent and a concentration-dependent manner. After 4 hours, the highest concentration of 4-HNE (50 μmol/L) produced 100% oligodendrocyte cell death. Data indicate that lipid peroxidation and production of 4-HNE occurs in white matter after cerebral ischemia and the lipid peroxidation by-product 4-HNE is toxic to axons and oligodendrocytes.

Axons and oligodendrocytes are vulnerable to cerebral ischemia. The absence of quantitative methods for assessment of white matter pathology in ischemia has precluded in vivo evaluation of therapeutic interventions directed at axons and oligodendrocytes. The authors demonstrate here that the quantitative extent of white matter pathology was reduced by restoration of cerebral blood flow after 2 hours of middle cerebral artery occlusion. Focal ischemia was induced in anesthetized rats by intraluminal thread placement, either transiently (for 2 hours) or permanently. At 24 hours after induction of ischemia, axonal damage was determined by amyloid precursor protein (APP) immunohistochemistry, and the ischemic insult to oligodendrocytes was assessed by Tau-1 immunostaining in the same sections. In adjacent sections, ischemic damage to neuronal perikarya was defined histologically. The hemispheric extent of axonal damage was reduced by 70% in the transiently occluded animals from that in permanently occluded animals. The volumes of oligodendrocyte pathology and of neuronal perikaryal damage were reduced by 62% and 58%, respectively, in the transiently occluded animals. These results demonstrate that this methodologic approach for assessing ischemic damage in axons and oligodendrocytes can detect relative alterations in gray and white matter pathology with intervention strategies.

Neuroprotection and anti-ischemic drug development A decade ago, there was little compelling evidence that pharmacological intervention could radically alter outcome after cerebral ischemia, even in experimental animals. By 1996, the pace of advance was such that a large number of drugs targeted at neurotransmitter receptors, and related mechanisms involved in ischemic damage, had advanced to clinical trials in stroke and head injury. The transformation of the pharmacology of cerebral ischemia had been achieved for two major reasons: first, the elucidation of neurochemical cascades initiated by ischemia, which revealed potential targets for intervention; and, second, the systematic assessment of drug efficacy using robust end-points (quantitative histopathology) in the most pertinent animal models. Since the elucidation of the excitotoxic cascade, numerous other pathological mechanisms have been identified by which neuroprotection can be achieved in ischemia. However, excitotoxicity remains central to current concepts of neuronal cell death and provides the prototype for anti-ischemic drug development for new pharmacological targets, i.e., reduction of the volume of neuronal perikaryal damage in models of focal cerebral ischemia. Animal models of focal cerebral ischemia are generally recognized as the most pertinent in relation to human stroke. The most widely used models of focal cerebral ischemia involve occlusion of the middle cerebral artery (MCA) either by surgical division or intraluminal suture placement.