The blood brain barrier: Its invincible susceptibility

Raenita Puliyelil
Life Sciences, Class of 2025, McMaster University

The blood brain barrier (BBB) is a specialized and dynamic network of brain microvascular endothelial cells (BMVEC) that serve critical functions of protecting the brain from harmful substances and supplying nutrients to neural tissue.1 Its ethereal complexity continues to intrigue scientists, neurologists, neurosurgeons and researchers alike. Due to the brain’s sophisticated system, it becomes prone to a spectrum of neurological disorders and diseases.

       The gradual deterioration of the integrity of the BBB is one of the most fundamental causes that contribute to the development of particular neural diseases.3 Recently, groundbreaking research has indicated that over the span of 2 years, significant leakage in the BBB is associated with extensive brain tissue damage in individuals with cerebral small vessel disease (cSVD) in comparison to patients with less leakage from the BBB.3 cSVD is just one of many diseases that affect the brain. As discussed by Lioutas et al, cSVD is a neurological disorder which affects the neural blood vessels.4 In particular, it refers to a category of various pathological processes with different aetiologies that impact the small arteries, arterioles, venules, and capillaries of the brain.5 Due to the difficulty of viewing small blood vessels in vivo, directly monitoring the natural progression of the disease becomes challenging.5 In most cases, cSVD tends to progress for a prolonged period of time during the early stage of the disease, as it initially remains asymptomatic.5 Based on prior studies, it has been reported that cSVD tends to act as a precursor to strokes and vascular dementia, primarily in elderly individuals.5 This malicious condition is characterized by the manifestation of lesions in the brain, known as white matter hyperintensities (WMHs).3 These lesions appear as areas of increased brightness when visualized through magnetic resonance imaging (MRI) and computed tomography (CT) and are utilized to gauge the severity of cSVD in patients.3

        In order to investigate the relationship between the amount of leakage in the BBB and the severity of brain tissue damage in cSVD patients, Kerkhofs et al. conducted a study with forty-three cSVD patients.3 The researchers utilized two types of brain imaging techniques, each of which were used for distinct purposes in the study. MRI was used to quantify the volume and rate of leakage in the BBB for each patient.3 Subsequently, patients had gone through intravoxel incoherent motion imaging (IVIM), which is an imaging technique that enables researchers to measure any alterations and stability of microstructure in the brain tissue surrounding WMH regions.3 This specific imaging technique was repeated on patients 2 years later in contemplation of further degeneration of brain tissue from the start of the study.3 As anticipated, the results supported the initial hypothesis. Specifically, for every 0.10% increase in discharge from the BBB, the diffusivity of brain tissue increased by 1.4% after two years since the beginning of the study.3 Ultimately, the results from this study supported the postulation that impairments in the BBB may influence the degeneration of brain tissue at an early stage in cSVD patients.3

        Previous research has suggested that the disruption of the BBB serves as one of the primary gateways for several notable neurological disorders. In addition to the latest discovery of the relationship between the permeability of the BBB and brain tissue damage in cSVD patients, the dysfunctioning of the BBB contributes to the development of neurodegenerative diseases such as epilepsy, Alzheimer’s, and dementia.6 In particular, prior studies have shown how traumatic and ischemic injuries and chronic stress jeopardizes the integrity of the BBB.6 This in turn makes the brain susceptible to the development and exacerbation of neural disorders.6 Fortunately, scientists have been able to advance their research in terms of looking into potential treatment methods and therapies for neurological diseases. Research conducted by Vliet, Aronica and Gorter (2015) have elicited promising findings for a novel therapy to treat epilepsy.7 Specifically, the use of new therapeutic strategies such as the inhibition of leukocyte-vascular interactions, mammalian target of rapamycin (mTOR) pathways, interleukin-1 receptors, TGF-β receptors and other components in contributing cellular pathways is aimed to restore the proper functioning of the BBB.7 As a result of this notable therapeutic discovery, the road to finding a treatment method for cSVD patients is sooner than expected.

1. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. (2006). Blood-brain barrier: structural components and function under physiologic and pathologic conditions. Journal of Neuroimmune Pharmacology, 1(3), 223-236.

2. Profaci CP, Munji RN, Pulido RS, and Daneman R. (2020). The blood-brain barrier in health and disease: Important unanswered questions. Journal of Experimental Medicine, 217(4), 1.

3. Kerkhofs D, Wong SM, Zhang E, Staals J, Jansen JFA, Oostenbrugge RJV, Backes WH. (2021). Baseline blood-brain barrier leakage and longitudinal microstructural tissue damage in the periphery of white matter hyperintensities. Neurology, 96(17), 1-4.

4. Lioutas VA, Wu B, Norton C, Helenius J, Modak J, Selim M. (2018). Cerebral small vessel disease burden and functional and radiographic outcomes in intracerebral hemorrhage. Journal of Neurology, 265(12), 2803-2814.

5. Pantoni L. (2010). Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. The Lancet Neurology, 9(7), 689-701.

6. Heinemann, Kaufer D, Friedman A. (2012). Blood-brain barrier dysfunction, TGFβ signaling, and astrocyte dysfunction in epilepsy. GLIA, 60(8), 1.

7. van Vliet EA, Aronica E, Gorter JA. (2015). Blood-brain barrier dysfunction, seizures and epilepsy. InSeminars in Cell & Developmental Biology, 38, 26-34.

%d bloggers like this: