The Blood–Brain Barrier as a Target in Traumatic Brain Injury Treatment

Thal, Serge C.; Neuhaus, Winfried

doi:10.1016/j.arcmed.2014.11.006

Cited by 118 publications

(90 citation statements)

References 135 publications

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“…When activated, they change their morphology to facilitate the migration toward the lesion site and the phagocytosis of cellular debris (Raivich 2005), and produce inflammatory cytokines and reactive oxygen species until weeks to months after TBI (Frugier et al 2010;Hsieh et al 2013). Blood-brain barrier and neurons can be disturbed by activated microglia and in turn aggravates brain injury (Thal and Neuhaus 2014;Block et al 2007;Hu et al 2015). In the current study, we showed reduced immunosignals of Iba-1 in PRE-084-treated TBI mice brains, which is in agreement with the previous report that PRE-084 reduced Iba1-positive microglial cells in SOD1-G93A mice (Mancuso et al 2012).…”

Section: Discussionmentioning

confidence: 98%

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Dong

Ren

et al. 2015

Cell Mol Neurobiol

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Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future.

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Section: Discussionmentioning

confidence: 98%

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Dong

Ren

et al. 2015

Cell Mol Neurobiol

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“…Mortality and permanent disability after traumatic brain injury (TBI) are major health challenges throughout the world [1–3]. Studies show that approximately 1.5 to 2 million patients suffer from TBI each year in the USA [4], and the total annual cost is estimated to be $10 billion [5].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Chinese Herbal Medicine Rhizoma drynariae in Rats After Traumatic Brain Injury and Identification of Active Compound

Wang

et al. 2015

Mol Neurobiol

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Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. Effective therapeutic strategies for TBI are needed, and increasing attention is turning toward traditional herbal medicine. Rhizoma drynariae is a traditional Chinese medicine that has immunomodulatory and anti-inflammatory effects. Here, using the controlled cortical impact model of TBI in rats, we examined whether oral administration of R. drynariae can reduce TBI-induced brain injury in rats. We also identified the likely active compound among its four major phytochemicals in decoction. We found that post-treatment with R. drynariae decreased brain lesion volume, improved neurologic and cognitive function, and reduced anxiety- and depression-like behaviors. These changes were accompanied by reduced blood levels of IL-6 and increased IL-10. R. drynariae treatment also reversed the TBI-induced decrease in blood monocyte numbers and percentage of blood CD3 and CD4 T lymphocytes while inhibiting microglial/macrophage activation. Furthermore, by using ultra performance liquid chromatography and comparing retention times with authentic standards, we identified eriodictyol as the putative active compound of R. drynariae extract in the blood of rats with TBI. These novel findings indicate that the traditional Chinese herbal medicine R. drynariae protects brain against TBI-induced brain injury, possibly via immune-promoting, anti-inflammatory, and neuroprotective effects. Eriodictyol could be its active compound.

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“…Adenosine triphosphate-binding cassette transporters prevent drug penetration across the BBB. In comparison with peripheral endothelial cells, the BBB endothelial cells are much more energy dependent, containing five to ten times the amount of mitochondria [3]. These endothelial cells are further covered by astrocyte end processes and have basal lamina shared with luminal pericytes.…”

Section: Physiologymentioning

confidence: 97%

“…The pathological consequence of BBB compromise is the exposure of the normally immunologically privileged central nervous system to an influx of neuroinflammatory cells and proinflammatory cytokines [2,3]. Neuroinflammation promotes vasogenic edema and co-exists with cytotoxic edema from cellular dysfunction and dysregulation of intracellular volume [4,5].…”

Section: Introductionmentioning

confidence: 99%

Assessing Blood Brain Barrier Permeability in Traumatic Brain Injury Research

et al. 2015

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The blood brain barrier plays an important role in traumatic brain injury, serving at the crossroads of secondary injury and potential therapies. In regards to trauma, this barrier contains an array of cellular and molecular components that protect the central nervous system from derangements in water homeostasis and inflammation. Preclinical and clinical assays have been developed to describe and quantify blood brain barrier permeability in relation to the integrity of these blood brain barrier components and the handling ofedema. This review will discuss both preclinical and clinical molecular and imaging techniques that are used to assess blood brain barrier function and recovery following traumatic brain injury.

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The Blood–Brain Barrier as a Target in Traumatic Brain Injury Treatment

Cited by 118 publications

References 135 publications

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Protective Effects of Chinese Herbal Medicine Rhizoma drynariae in Rats After Traumatic Brain Injury and Identification of Active Compound

Assessing Blood Brain Barrier Permeability in Traumatic Brain Injury Research

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