Longitudinal Characterization of Blood–Brain Barrier Permeability after Experimental Traumatic Brain Injury by <i>In Vivo</i> 2-Photon Microscopy

Hu, Yue; Seker, Burcu; Exner, Carina; Zhang, Junping; Plesnila, Nikolaus; Schwarzmaier, Susanne M.

doi:10.1089/neu.2020.7271

Cited by 9 publications

(5 citation statements)

References 59 publications

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“…There is evidence that the craniotomy is not atraumatic and the effects of surgery should be controlled [73]. However, recently in vivo study of CCI model showed that no pathology was present in sham operated mice (craniotomy only) by MRI scan [74]. To mitigate these concerns to some extent, we included the craniotomy surgical sham groups as control in our study.…”

Section: Discussionmentioning

confidence: 99%

Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury

Gu,

Yan,

Tang

et al. 2024

J Neuroinflammation

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Background The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway. Methods In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing. Results P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris’s water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements. Conclusions We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.

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Section: Discussionmentioning

confidence: 99%

Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury

Gu,

Yan,

Tang

et al. 2024

J Neuroinflammation

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“…BBB disruption can manifest as a transient event with minor consequences on normal brain function or lead on to a chronic or total breakdown of the barrier properties, resulting in significant and/or irreversible brain damage. In neurological diseases such as stroke [122][123][124][125][126], traumatic brain injury [127,128] and Alzheimer's disease [129], as well as in some neurological infections [130], BBB disruption has been demonstrated to be biphasic in nature. For example, experimental studies in ischaemic stroke have provided extensive evidence that demonstrates an early opening of the BBB within the first 4-6 h of a stroke is followed by a refractory period and then a late opening ∼48-72 h [131,132].…”

Section: Timing and Extent Of Bbb Disruption During Neurological Diseasementioning

confidence: 99%

The role of the blood–brain barrier during neurological disease and infection

Patabendige

Janigro

2023

Biochemical Society Transactions

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A healthy brain is protected by the blood–brain barrier (BBB), which is formed by the endothelial cells that line brain capillaries. The BBB plays an extremely important role in supporting normal neuronal function by maintaining the homeostasis of the brain microenvironment and restricting pathogen and toxin entry to the brain. Dysfunction of this highly complex and regulated structure can be life threatening. BBB dysfunction is implicated in many neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, and brain infections. Among other mechanisms, inflammation and/or flow disturbances are major causes of BBB dysfunction in neurological infections and diseases. In particular, in ischaemic stroke, both inflammation and flow disturbances contribute to BBB disruption, leading to devastating consequences. While a transient or minor disruption to the barrier function could be tolerated, chronic or a total breach of the barrier can result in irreversible brain damage. It is worth noting that timing and extent of BBB disruption play an important role in the process of any repair of brain damage and treatment strategies. This review evaluates and summarises some of the latest research on the role of the BBB during neurological disease and infection with a focus on the effects of inflammation and flow disturbances on the BBB. The BBB's crucial role in protecting the brain is also the bottleneck in central nervous system drug development. Therefore, innovative strategies to carry therapeutics across the BBB and novel models to screen drugs, and to study the complex, overlapping mechanisms of BBB disruption are urgently needed.

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“…In patients with severe TBI, a biphasic phenomenon is observed. 34,35 Within hours, vasogenic brain edema occurs, followed by a later phase that starts about 3-7 days after injury and exhibits an inflammatory component that may last for weeks. 36 Damaged endothelium and mechanical disruption of the BBB lead to the early phase of edema generation because large molecules and proteins permeate into the cerebral tissue and change the hydrostatic-colloid osmotic equilibrium.…”

Section: Future and Experimental Directions Blood Brain Barrier As A ...mentioning

confidence: 99%

Neurovascular Interventions for Neurotrauma: From Treatment of Injured Vessels to Treatment of the Injured Brain?

Doron,

Patel,

Hawryluk

2023

Operative Neurosurgery

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Traumatic brain injury is often associated with a direct or secondary neurovascular pathology. In this review, we present recent advancements in endovascular neurosurgery that enable accurate and effective vessel reconstruction with emphasis on its role in early diagnosis, the expanding use of flow diversion in pseudoaneurysms, and traumatic arteriovenous fistulas. In addition, future directions in which catheter-based interventions could potentially affect traumatic brain injury are described: targeting blood brain barrier integrity using the advantages of intra-arterial drug delivery of blood brain barrier stabilizers to prevent secondary brain edema, exploring the impact of endovascular venous access as a means to modulate venous outflow in an attempt to reduce intracranial pressure and augment brain perfusion, applying selective intra-arterial hypothermia as a neuroprotection method mitigating some of the risks conferred by systemic cooling, trans-vessel wall delivery of regenerative therapy agents, and shifting attention using multimodal neuromonitoring to post-traumatic vasospasm to further characterize the role it plays in secondary brain injury. Thus, we believe that the potential of endovascular tools can be expanded because they enable access to the “highways” governing perfusion and flow and call for further research focused on exploring these routes because it may contribute to novel endovascular approaches currently used for treating injured vessels, harnessing them for treatment of the injured brain.

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Longitudinal Characterization of Blood–Brain Barrier Permeability after Experimental Traumatic Brain Injury by In Vivo 2-Photon Microscopy

Cited by 9 publications

References 59 publications

Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury

Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury

The role of the blood–brain barrier during neurological disease and infection

Neurovascular Interventions for Neurotrauma: From Treatment of Injured Vessels to Treatment of the Injured Brain?

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