The blood-brain barrier, as detailed in our previous article, is a vitally important "gatekeeper" that separates the central nervous system (CNS) from the peripheral tissues [1].
In support of the normal healthy function of the CNS, the blood-brain barrier governs material, nutrient, and cell transfer from the blood to the brain and vice versa. It restricts the entry of peripheral inflammatory mediators (e.g., cytokines, antibodies, etc.), which can impair neurotransmission [2]. The blood-brain barrier also participates in the clearance of cellular metabolites and toxins from the brain to the blood and regulates the composition and volume of cerebrospinal fluid.
Disturbances of the blood-brain barrier commonly occur in neuronal dysfunction, neuroinflammation, and neurodegeneration, but others include trauma, hypoxia, infection, activation of the clotting system, dietary components, environmental toxins, and genetics [3]. There is a particular link between high-grade inflammation (in conditions such as meningitis, encephalitis, sepsis, and local and systemic infections) and increased permeability of the blood-brain barrier. Interestingly, however, low-grade systemic inflammation can also contribute towards impaired blood-brain barrier function, which is notable given its prevalence in metabolic and other diseases that are a key feature of the population in Western nations [4].
The disruption of the blood-brain barrier entails a reduction in barrier tightness and increased leakiness, and as a consequence, the impaired integrity of the blood-brain barrier allows for the entrance of cytokines and immune cells into the CNS, which has secondary downstream effects [1,5].
In today’s article, we will briefly discuss five methods or lifestyle aspects that can potentially address issues with the blood-brain barrier, such as restoring a compromised blood-brain barrier and/or supporting blood-brain barrier permeability and optimal function.
1. Engage in Physical Exercise for Better Brain Function
Exercise training is an important behavioral intervention that has a wide range of beneficial health effects. Research shows that physical activity of this kind leads to systemic adaptations in the body and an elongated healthspan (the amount of time we spend in good health throughout our life) across different human populations [6,7].
Ample evidence indicates that engaging in physical exercise promotes the health of essentially every organ system, with multifaceted benefits for healthspan [7]. These include but are not limited to the improvement of cardiovascular risk factors, inflammation, mitochondrial quality, and insulin sensitivity.
Physical exercise influences the blood-brain barrier through several anti-inflammatory effects and leads to a reduction in lesions and vascular permeability [1]. Blood-brain barrier breakdown generally brings about neuronal dysfunction, neuroinflammation, and neurodegeneration. Inflammation is a starting point in the pathogenesis of numerous diseases and there is considerable interest in non-pharmacological methods to treat it.
Regular physical exercise reduces blood-brain barrier permeability due to its effect on antioxidative capacity, oxidative stress, and anti-inflammatory actions. However, although physical exercise has positive effects on brain function, there are limited published studies on the long-term consequences of physical activity on blood-brain barrier permeability. After 8 weeks of training in multiple sclerosis patients, an improvement in blood-brain barrier leakage markers such as S100B has been observed [8]. Elsewhere, rodent work has shown that four weeks of exercise can help maintain blood-brain barrier integrity by preserving the tight junctions of the blood-brain barrier [9]. Future research needs to link blood-brain barrier permeability with clinical conditions and establish tangible benefits for patients. However, the undeniable benefits of physical exercise for systemic health warrant its inclusion in any lifestyle modifications.
2. Vitamin B6, B12, and Folate to Improve Blood-Brain Barrier Function
The B vitamins are an integral component of a healthy diet, with all serving as cofactors for key metabolic processes in the body or as precursors for the cofactors themselves [10]. In conditions of deficiency in vitamin B6, B12, and folate, there is evidence that blood-brain barrier integrity can be negatively affected. Decreased levels of B12 and folate in particular can increase levels of homocysteine, a pro-inflammatory endogenous amino acid, and lead to alterations in blood-brain barrier function [11]. In patients with mild cognitive impairment and elevated levels of homocysteine, a vitamin B12-B6-folate supplement was shown to improve blood-brain barrier function and stabilize cognitive status [12]. B vitamins are found in protein-rich foods as well as fortified food items such as breakfast cereals and baked goods, although overall the latter foods are to be avoided due to sugar and processed ingredients (both of which can contribute to inflammation).
3. Vitamin D to Protect the Blood-Brain Barrier
The major natural source of vitamin D is the synthesis in the skin via exposure to ultraviolet-B (UVB) radiation or sunlight. It can also be obtained in the diet from foods such as eggs, fatty fish, and from supplements. It is fat-soluble and has been referred to as a steroid hormone given its far-reaching roles in the body and mode of synthesis.
In a rat model, vitamin D3 supplementation was shown to increase serum levels of vitamin D after one week, which led to the amelioration of neurological deficits and cognitive impairment brought about by a traumatic brain injury. It also reduced brain edema, blood-brain barrier impairment, and decreased inflammation following the injury [13]. It might therefore offer protective value against blood-brain barrier impairments, especially following traumatic brain injury.
4. Resveratrol to Maintain the Blood-Brain Barrier
Resveratrol is a chemical found mostly in the skin of grapes and other berries, as well as products made from them. It is a polyphenol that has been studied for the last 25 years as a potential anti-aging compound [14]. In a rat model of multiple sclerosis, it has been shown to have protective effects on the blood-brain barrier tight junction as well as anti-inflammatory and antioxidant activity that all serve to enhance blood-brain barrier integrity [15]. Although the research is still in the preclinical stages, resveratrol could have important roles in the maintenance of the blood-brain barrier and its optimal function.
5. Obtain Adequate Quality Sleep to Enhance Brain Health
The blood-brain barrier controls permeability into and out of the nervous system. Recent evidence suggests that permeability at the blood-brain barrier is dynamically controlled by circadian rhythms and sleep [16]. An endogenous circadian rhythm within the blood-brain barrier is responsible for controlling the function of transporters, therefore regulating blood-brain barrier permeability. Sleep also promotes the clearance of metabolites along the blood-brain barrier [17] and enables endocytosis there as well [16,18]. Endocytosis is increased during sleep, and inhibition of this process increases the need for sleep [18]. Disruption of sleep can not only impair these essential roles but also lead to the breakdown of the blood-brain barrier [16]. Although much of this research is in its infancy, it seems that the primary restorative function of sleep could be to enhance the removal of potentially neurotoxic waste products that accumulate in the CNS while awake [17].
Summary
In this article, we have examined some lifestyle and dietary aspects that can be modified to support the health, healing, and optimal function of the blood-brain barrier. These include the consumption of adequate vitamins (B6, B12, folate, and D), as well as the plant polyphenol resveratrol. Alongside these dietary considerations, the two clear lifestyle factors that contribute to blood-brain barrier health and integrity are adequate sleep and engaging in regular physical exercise. Not only will these modifications help with the blood-brain barrier, but they will also offer multifaceted benefits across the spectrum of health.
References
[1] M.A. Małkiewicz, A. Szarmach, A. Sabisz, W.J. Cubała, E. Szurowska, P.J. Winklewski, Blood-brain barrier permeability and physical exercise, J Neuroinflammation 16 (2019) 15. https://doi.org/10.1186/s12974-019-1403-x.
[2] N.J. Abbott, L. Rönnbäck, E. Hansson, Astrocyte-endothelial interactions at the blood-brain barrier, Nat Rev Neurosci 7 (2006) 41–53. https://doi.org/10.1038/nrn1824.
[3] D. Shlosberg, M. Benifla, D. Kaufer, A. Friedman, Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury, Nat Rev Neurol 6 (2010) 393–403. https://doi.org/10.1038/nrneurol.2010.74.
[4] J.I. León-Pedroza, L.A. González-Tapia, E. Del Olmo-Gil, D. Castellanos-Rodríguez, G. Escobedo, A. González-Chávez, Low-grade systemic inflammation and the development of metabolic diseases: From the molecular evidence to the clinical practice, Cirugía y Cirujanos (English Edition) 83 (2015) 543–551. https://doi.org/10.1016/j.circen.2015.11.008.
[5] K.M. Baeten, K. Akassoglou, Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke, Dev Neurobiol 71 (2011) 1018–1039. https://doi.org/10.1002/dneu.20954.
[6] D. Szalewska, M. Radkowski, U. Demkow, P.J. Winklewski, Exercise Strategies to Counteract Brain Aging Effects, Adv Exp Med Biol 1020 (2017) 69–79. https://doi.org/10.1007/5584_2017_3.
[7] Y. Guan, Z. Yan, Molecular Mechanisms of Exercise and Healthspan, Cells 11 (2022) 872. https://doi.org/10.3390/cells11050872.
[8] M. Mokhtarzade, R. Motl, R. Negaresh, P. Zimmer, M. Khodadoost, J.S. Baker, D. Patel, N. Majdinasab, R. Ranjbar, Exercise-induced changes in neurotrophic factors and markers of blood-brain barrier permeability are moderated by weight status in multiple sclerosis, Neuropeptides 70 (2018) 93–100. https://doi.org/10.1016/j.npep.2018.05.010.
[9] P.S. Souza, E.D. Gonçalves, G.S. Pedroso, H.R. Farias, S.C. Junqueira, R. Marcon, T. Tuon, M. Cola, P.C.L. Silveira, A.R. Santos, J.B. Calixto, C.T. Souza, R.A. De Pinho, R.C. Dutra, Physical Exercise Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Peripheral Immune Response and Blood-Brain Barrier Disruption, Mol Neurobiol 54 (2017) 4723–4737. https://doi.org/10.1007/s12035-016-0014-0.
[10] M. Hanna, E. Jaqua, V. Nguyen, J. Clay, B Vitamins: Functions and Uses in Medicine, Perm J 26 (2022) 89–97. https://doi.org/10.7812/TPP/21.204.
[11] M. Campana, L. Löhrs, J. Strauß, S. Münz, T. Oviedo-Salcedo, P. Fernando, I. Maurus, F. Raabe, J. Moussiopoulou, P. Eichhorn, P. Falkai, A. Hasan, E. Wagner, Blood–brain barrier dysfunction and folate and vitamin B12 levels in first-episode schizophrenia-spectrum psychosis: a retrospective chart review, Eur Arch Psychiatry Clin Neurosci 273 (2023) 1693–1701. https://doi.org/10.1007/s00406-023-01572-3.
[12] M. Lehmann, B. Regland, K. Blennow, C.G. Gottfries, Vitamin B12-B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment, Dement Geriatr Cogn Disord 16 (2003) 145–150. https://doi.org/10.1159/000071002.
[13] J. Yang, K. Wang, T. Hu, G. Wang, W. Wang, J. Zhang, Vitamin D3 Supplement Attenuates Blood-Brain Barrier Disruption and Cognitive Impairments in a Rat Model of Traumatic Brain Injury, Neuromolecular Med 23 (2021) 491–499. https://doi.org/10.1007/s12017-021-08649-z.
[14] R. Hosoda, R. Nakashima, M. Yano, N. Iwahara, S. Asakura, I. Nojima, Y. Saga, R. Kunimoto, Y. Horio, A. Kuno, Resveratrol, a SIRT1 activator, attenuates aging-associated alterations in skeletal muscle and heart in mice, J Pharmacol Sci 152 (2023) 112–122. https://doi.org/10.1016/j.jphs.2023.04.001.
[15] D. Wang, S.-P. Li, J.-S. Fu, S. Zhang, L. Bai, L. Guo, Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice, Journal of Neurophysiology 116 (2016) 2173–2179. https://doi.org/10.1152/jn.00510.2016.
[16] V.A. Cuddapah, S.L. Zhang, A. Sehgal, Regulation of the Blood-Brain Barrier by Circadian Rhythms and Sleep, Trends Neurosci 42 (2019) 500–510. https://doi.org/10.1016/j.tins.2019.05.001.
[17] L. Xie, H. Kang, Q. Xu, M.J. Chen, Y. Liao, M. Thiyagarajan, J. O’Donnell, D.J. Christensen, C. Nicholson, J.J. Iliff, T. Takano, R. Deane, M. Nedergaard, Sleep drives metabolite clearance from the adult brain, Science 342 (2013) 373–377. https://doi.org/10.1126/science.1241224.
[18] G. Artiushin, S.L. Zhang, H. Tricoire, A. Sehgal, Endocytosis at the Drosophila blood-brain barrier as a function for sleep, Elife 7 (2018) e43326. https://doi.org/10.7554/eLife.43326.
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