Neuroinflammation is a term used to describe the broad range of immune responses of the central nervous system (CNS) which cause synaptic dysfunction and neuronal death (1,2). It is central to the common pathology of several acute and chronic brain diseases (Table 1).

• The principal cells involved are the microglia  and astrocytes .
• The blood brain barrier (BBB) is permeable to pro-inflammatory mediators derived from peripheral inflammation. Chronic systemic inflammation compromises the integrity of the BBB.
• Neuroinflammation may protect the brain, depending on the type and extent of stimulation (3,4,5).
  • Acute inflammation triggers neuroprotective repair responses, immune conditioning and brain plasticity.
  • If uncontrolled and persistent, hyper-inflammatory responses accelerate the ageing process of the brain, resulting in brain damage and prolonged neurological deficits.

The nutritional impact on neuroinflammation is considered a therapeutic strategy in neurodegenerative and neuropsychiatric disease prevention and management (6).

Table 1. Disorders associated with neuroinflammation (3,6,7,8,9,10,11,12,13,14)

Traditional Understanding

Inflammatory cytokines and other proteins were originally thought to be too large to pass through the BBB, however active transport systems have been observed facilitating the delivery of inflammatory cytokines into the brain (10,15).

Latest Research

Beneficial Factors

Many dietary components have been shown to reduce oxidative stress and neuroinflammation, provide protection from cellular damage and improve cognitive function (16). The latest research focusses on anti-inflammatory and/or antioxidant dietary patterns/nutrients.

Polyunsaturated fatty acids (PUFAs)

DHA and EPA can reduce neuroinflammation and cognitive decline (17).

• EPA positively influences mood disorders, whereas DHA maintains normal brain structure (18,19,20).
• 90% of studies found a significant decrease of microglial density  and/or activation after exposure to omega-3 PUFAs (21).
• Omega-3 long-chain PUFAs and their bioactive lipid derivatives, specialized pro-resolving mediators (SPMs), show promise for reducing and resolving inflammation, particularly neuroinflammation associated with ageing (22).

Antioxidants

Antioxidants reduce both systemic inflammation and neuroinflammation (2) and are capable of inhibiting, preventing and/or repairing damage induced by neuroinflammation (23). Recent research has focussed on the following antioxidants, polyphenols and flavonoids:

• Quercetin (24)
• Vitamin C (25)
• Resveratrol (26,27,28)
• Retinoids and carotenoids (e.g. astaxanthin, lutein, retinoic acid) (29,30)
• Epigallocatechin-gallate (EGCG) (31)
• Luteolin (24,32)
• Apigenin (33)
• Cocoa flavanols (34)

Other

• Extra-virgin olive oil (35,36)
• Zinc (37)
• Tocotrienols (38)
• Folic Acid (39)
• Mediterranean Diet (23,40)
• Ketogenic Diet (41,42)
• MIND Diet (Mediterranean-DASH diet Intervention for Neurodegenerative Delay) (43,44)

Detrimental Factors

The following factors have been found to have a detrimental effect on neuroinflammation pathophysiology and consequences:

• Thiamine deficiency (45)
• High salt or long-chain fatty acid intake (46)
• Fluorine (47)
• Chronic alcohol abuse (48)
• Hypoglycaemic damage to the BBB (49,50)
• Western diet (excessive consumption of saturated fats and sugars) (51,52,53)
• Obesity (32,40)

Hypothalamic inflammation

Neuroinflammation of the hypothalamus can be triggered in response to the consumption of large amounts of dietary fat, particularly saturated fats (54,55,56).

• Hypothalamic inflammation is an important mechanism in the development of leptin  resistance in obesity and in regulating body energy stores (55). It can impair insulin release from β cells, impair peripheral insulin action, and promote hypertension (57).
• Obesity-derived neuroinflammation affects other brain structures apart from the hypothalamus, such as the hippocampus, cortex, brainstem, or amygdala (58).

Gut-brain axis

The composition of the intestinal microbiota may play a key role in modulating neuroinflammation (59,60).

• The gut microbiota plays a key role in the activation and modulation of microglia (11,61). Manipulation of the gut microbiome, especially with short chain fatty acid-producing bacteria, could modulate neuroimmune activation (62).
• Age related alterations in the gut microbiota may contribute to neuroinflammation in AD (63).
• The microbiota are important for the bioavailability of polyphenols, the majority of which are fermented by the gut microbiota (64).
• Peripheral inflammatory stimuli, such as lipopolysaccharides (LPS), cause a profound immunological response in the brain resulting in microglial activation (10,63,65).
• Dysbiosis contributes to gut inflammation, generation of LPS and pro-inflammatory cytokines, gut permeability, and systemic- and neuro-inflammation (57).

Figure 1. Diet-microbiome interactions in neuroinflammation (66) CC BY 4.0

Experimental Studies

• Vitamin B₆ has anti-inflammatory and antioxidant properties and improves neuroinflammation (67).
• Naringenin, a citrus fruit flavanone, regulates neuroinflammation and oxidative stress (68,69).
• Magnesium-L-threonate suppresses the expression and production of inflammatory cytokines in the brain (70).
• Vitamin D suppresses ROS generation and inflammatory cytokines especially in combination with vitamin A and omega-3 PUFAs (71,72).
• Curcumin down regulates the expression of COX-2 and pro-inflammatory cytokines in activated microglia, decreases the production of ROS and activates the Nrf2 pathway (24,73,74,75,76).
• Pomegranate polyphenols reduce neuroinflammation (77).
• Walnuts demonstrate anti-inflammatory and antioxidative properties, improving memory deficits associated with neuroinflammation (78,79).
• An omega-3 PUFA-enriched diet attenuates short and long-term behavioural deficits and reduces the neuroinflammatory response after traumatic brain injury (80).
• Impaired synthesis of DHA affects neural plasticity and inflammation in the brain (81).
• Epigallocatechin-gallate (EGCG) limits inflammatory lesions in the spinal cord and reduces disease severity in multiple sclerosis (82).
• Bilberry (Vaccinium myrtillus L.) anthocyanin consumption decreases hippocampal neuroinflammatory responses and reverses cognitive dysfunction in Alzheimer’s disease via inducing microglial phagocytosis of beta-amyloid protein plaques (83).
• Tart cherries (Prunus Cerasus L.) show promise in preventing obesity-related neuroinflammation. Tart cherries are rich in anthocyanins and components that modify lipid metabolism (84).
• Ferulic and caffeic acid inhibit microglial inflammation (85,86).
• Krill oil protects against cognitive impairment via anti-inflammatory action (87).
• Obesity in aging is associated with a heightened state of systemic inflammation which exacerbates BBB disruption (88).
• High fibre diets prevent neuroinflammation and cognitive decline in obesity by modulating the gut microbiome and gut-brain axis (89).
• High-refined carbohydrate diets induce neuroinflammation via the release of pro-inflammatory cytokines in microglia (90).