Blood–brain barrier and traumatic brain injury

Abstract

The blood-brain barrier (BBB) is an anatomical microstructural unit, with several different components playing key roles in normal brain physiological regulation. Formed by tightly connected cerebrovascular endothelial cells, its normal function depends on paracrine interactions between endothelium and closely related glia, with several recent reports stressing the need to consider the entire gliovascular unit in order to explain the underlying cellular and molecular mechanisms. Despite that, with regard to traumatic brain injury (TBI) and significant events in incidence and potential clinical consequences in pediatric and adult ages, little is known about the actual role of BBB disruption in its diverse pathological pathways. This Mini-Review addresses the current literature on possible factors affecting gliovascular units and contributing to posttraumatic BBB dysfunction, including neuroinflammation and disturbed transport mechanisms along with altered permeability and consequent posttraumatic edema. Key mechanisms and its components are described, and promising lines of basic and clinical research are identified, because further knowledge on BBB pathological interference should play a key role in understanding TBI and provide a basis for possible therapeutic targets in the near future, whether through restoration of normal BBB function after injury or delivering drugs in an increased permeability context, preventing secondary damage and improving functional outcome.

An investigation of neuroinjury biomarkers after sport-related concussion: from the subacute phase to clinical recovery

“…Median total symptoms and symptom severity were 7.5 (IQR 5 -13) and 12.0 (IQR 5.3 -22.6), respectively, at the time of medical evaluation. At the time of blood sampling, the median total symptoms reported by athletes with SRC was 5 (IQR 4-11), and the median symptom severity was 8 (IQR [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. At the time of blood sampling, compared to healthy controls, athletes with SRC had significantly higher total symptoms scores (median score = 5.0 vs. 3.0 respectively; p = 0.04, data not shown) but not symptom severity scores.…”

“…Multiple lines of evidence suggest that markers reflecting brain injury and repair may appear in the peripheral circulation through several mechanisms, including transport across a disrupted blood-brain barrier (BBB) (15)(16)(17), glymphatic clearance (18), or aberrant neuroendocrine signalling (19)(20)(21).…”

Osthole, a Natural Coumarin Improves Cognitive Impairments and BBB Dysfunction After Transient Global Brain Ischemia in C57 BL/6J Mice: Involvement of Nrf2 Pathway

“…Sham: sham-operated animals, Model: animals of vehicle treatment and ischemia, osthole: animals of osthole treatment and ischemia oxidative stress induced by moderate hypoxia can breakdown the BBB integrity in brain endothelial cells (BEC) [38]. Another study showed that peroxidation of membrane polyunsaturated fatty acids induced by ROS may affect BBB function by active aldehydes, such as 4-hydroxynonenal (4-HNE), which can significantly increase endothelial monolayer permeability in experimental studies [1]. Moreover, the brain endothelium has been identified as a major source of ROS production in cerebral ischemia that aggravates cerebral blood flow impairment in reperfusion [37].…”

Isoliquiritigenin Attenuates Neuroinflammation in Traumatic Brain Injury in Young Rats

“…At 24 h after TBI, the rats were anesthetized and cerebrospinal fluid (CSF) was collected from the cisterna magna, following the protocol of a previous study [3]. The contents of TNF-α, IFN-γ, IL-1β, and IL-10 in the CSF were assessed using commercial ELISA kits (Boster Biological Technology, Wuhan, Hubei, China), following the manufacturer’s protocol.…”

“…It is the first-ranking cause of death in US children [1] and a common cause of death in young male adults worldwide [2]. Survivors of TBI usually continue to suffer short- or long-term disabilities including motor and cognitive deficits [3]. Inflammation and apoptosis play a critical role in the pathological progress of TBI [4, 5].…”