Human Milk Oligosaccharide 2′-Fucosyllactose Induces Neuroprotection from Intracerebral Hemorrhage Stroke

Abstract

Intracerebral hemorrhage (ICH) occurs when brain blood vessels rupture, causing inflammation and cell death. 2-Fucosyllactose (2FL), a human milk oligosaccharide, has potent antiapoptotic and anti-inflammatory effects. The purpose of this study was to examine the protective effect of 2FL in cellular and rodent models of ICH. Hemin was added to a primary rat cortical neuronal and BV2 microglia coculture to simulate ICH in vitro. IBA1 and MAP2 immunoreactivities were used to determine inflammation and neuronal survival. Hemin significantly increased IBA1, while it reduced MAP2 immunoreactivity. 2FL significantly antagonized both responses. The protective effect of 2FL was next examined in a rat ICH model. Intracerebral administration of type VII collagenase reduced open-field locomotor activity. Early post-treatment with 2FL significantly improved locomotor activity. Brain tissues were collected for immunohistochemistry and qRT-PCR analysis. 2FL reduced IBA1 and CD4 immunoreactivity in the lesioned striatum. 2FL downregulated the expression of ER stress markers (PERK and CHOP), while it upregulated M2 macrophage markers (CD206 and TGFβ) in the lesioned brain. Taken together, our data support that 2FL has a neuroprotective effect against ICH through the inhibition of neuroinflammation and ER stress. 2FL may have clinical implications for the treatment of ICH.

Review on the Impact of Milk Oligosaccharides on the Brain and Neurocognitive Development in Early Life

“…Many studies included in this review supported the role of 2 -FL and fucosylated HMOS in learning and memory formation processes [53,[59][60][61][62]66,67]. This may be explained by the neuroprotective effects of 2 -FL in animal models [99,100], although the exact mechanism for this effect is unclear. LTP is often considered the cellular analog of learning and memory [101] and is widely used to assess synaptic transmission in neurons [102].…”

Herbal formula PM012 induces neuroprotection in stroke brain

“…Inflammation and ER stress are major causes of neurodegeneration after ischemic brain injury. We and others reported that suppression of inflammation or ER stress improved neural functions in stroke animals [ 11 , 16 ]. These data suggest that paeoniflorin and 5-hydroxymethylfurfural are the active ingredients in PM012, which may induce protection against ischemic brain injury through anti-inflammation and anti-ER stress.…”

“…Suppressing these processes prevents stroke-mediated degeneration. For example, we previously reported that 2-fucosyllactose reduced ischemia-mediated ER stress and inflammation in brain and improved locomotor behavior in stroke rats [ 11 ]. Interestingly, several active ingredients in PM012 also process anti-inflammatory or anti-ER stress properties [ 12 , 13 ].…”

A unique role for Clostridium perfringens in the digestion of HMOs

“…Aside from protecting against necrotising enterocolitis [6] or Streptococcus group B [7], HMOs may also provide other benefits to the neonate, including in neurodevelopment [8,9] and prevention of allergic diseases [10][11][12]. The development of a healthy gut microbiome, as a consequence of human milk oligosaccharides in the diet, has indications of longer-term benefit to the infant, including reduced incidence of inflammatory bowel diseases [13], neuroprotective effects [14] and small-molecule homeostasis [15]. In this context, understanding the principles of HMO synthesis as well as the conditions upon which HMOs are potentially digested by the infant gut [16], is a step towards answering the broad range of open questions.…”