The International Brain Barriers Society (IBBS) is a new organisation that addresses the scientific and clinical needs for research into brain barriers. The IBBS panel initially identified 12 topics as priorities to advance the field of brain barrier research and treat CNS disease. These topics were then narrowed down to the six topics deemed to be the most clinically relevant to the field: inflammation, injury, tumours, neurodegeneration, specialised neural barriers, and delivery. A
ReviewStrategies to advance translational research into brain barriers
Introduction
The difficulty in delivering therapeutic drugs to the CNS is deemed by many researchers to contribute to the limited success of neurotherapeutics. In their neuroprotective role, the blood–brain barrier (BBB), the blood–CSF barrier, and the other specialised brain barriers hinder the delivery of many potentially important diagnostic and therapeutic drugs to the CNS. The effective delivery of molecules and genes to the CNS is problematic and will require a concerted effort among academia, governments, and industry. The aims of this Review are to outline current research in the field of brain barriers, the main advances made since 2000, the barriers to progress, and to recommend research priorities and the resources needed to advance the field.
Section snippets
Inflammation and brain barriers
The BBB and the neurovascular unit (NVU) are involved in various neuroinflammatory processes, and the pathophysiology at most brain barriers is affected by neuroinflammation.1 Inflammatory events probably occur at the blood–retinal barrier and other specialised barriers.2, 3 One of the unifying concepts in brain barrier research is the neuroinflammatory interactions with the BBB; for example, the involvement of brain barriers in neurodegenerative diseases, CNS injury, neuroendocrine secretions,
Injury and the brain barriers
Neurotrauma and related neuropathological events (stroke, head injury, ischaemia and reperfusion, haemorrhage, and infarction) share a common feature: the alteration of the BBB at and around the site of injury.17 The brain barriers have important roles in the overall homoeostasis of the CNS, which include regulation of the exchange of nutrients, ions, water, metabolites, and xenobiotics between the blood and the CNS1, 18 and the prevention of entry of potentially neurotoxic plasma constituents
Tumours and the brain barriers
The study of the BBB is crucial to understand and manage primary and metastatic brain tumours. Many factors that modify vascular endothelial function and the tightness of the barrier in brain tumours have been identified;30 physiological factors,31 including tumour interstitial fluid pressure, markedly influence drug penetration into tumours.32 The complex pathophysiology of the blood–tumour barrier can be manipulated to improve our knowledge and management of brain tumours. Neuroimaging shows
Neurodegenerative diseases and brain barriers
Research to understand the pathogenesis of neurodegenerative diseases and to design effective therapies has focused mainly on neurons. This neurocentric view has contributed to our knowledge of neuronal dysfunction, neuronal death pathways, and the accumulation of proteinaceous aggregates during chronic neurodegenerative processes; however, this approach has not resulted in therapeutics that modify the disease. The pathogenesis of neurodegenerative disorders (figure 5) is more complex than
Specialised neural barriers
Specialised neural barriers comprise the only interface between the blood and neural tissue, apart from the endothelium of the brain parenchymal capillaries. These specialised neural barriers include the blood–CSF barrier (choroid plexus epithelium), the meninges and the blood–subarachnoid CSF barrier, the blood–retinal barrier (retinal capillary endothelium and retinal pigment epithelium), the blood–nerve barrier (endoneural capillary endothelium and perineurium), the blood–labyrinth barriers
Delivery of drugs to the brain
Delivery of therapeutic compounds to the brain is complicated.35, 67 Despite great strides in the basic science of brain physiology and disease in the past decade, problems of delivery have received negligible attention. Current estimates are that 98% of all small molecule drugs cross the BBB only negligibly, and miniscule amounts of large molecule drugs cross the BBB, except when dysfunction of the BBB causes leakeage or at those sites with transport systems. This has slowed the application of
Conclusions
Several common themes and topic-specific needs are priorities to advance the field of brain barrier research. Cross-topical themes include advances in imaging techniques, characterisation of the mechanisms, problems of the delivery of therapeutics, training of new investigators, and building of consortiums among institutions and laboratories. The cited reports that accompany this synopsis (see panel) should be consulted for more details on each topic. Clearly, brain barriers are more than just
Search strategy and selection criteria
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