The Relationship Between Penumbral Tissue and Blood-Brain Barrier Disruption in Acute Stroke Patients Presenting in an Extended Time Window

Heidari, Parisa; Blayney, Sarah; Butler, Jarrhett; Hitomi, Emi; Luby, Marie; Leigh, R. John

doi:10.3389/fneur.2020.582994

Cited by 12 publications

(8 citation statements)

References 16 publications

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“…However, patients exhibiting a cerebral perfusion deficit, such as in acute stroke, require an arrival time correction for DSC-based permeability imaging to control for altered blood flow effects before calculating the permeability signal [103,105]. Both the DCE-PWI and delay-corrected DSC-PWI techniques to assess BBB permeability have successfully been applied successfully to investigate pre-and post-treatment BBB leakage in previous studies, which demonstrated associations between BBB disruption and haemorrhagic transformation, parenchymal haemorrhage, and unfavourable clinical outcomes [102,104,105,107,108] (Fig. 4).…”

Section: Blood-brain Barrier Dysfunction and Post-stroke Seizuresmentioning

confidence: 99%

“…4). Furthermore, a high magnitude of BBB disruption correlates with the degree of hypoperfusion and is associated with poor collateral flow [102], whereas a favourable penumbral profile that predicts a favourable clinical outcome is associated with reduced BBB disruption [108]. As the clinical stroke severity influences the PSE risk, this suggests a link between BBB disruption and PSE.…”

Section: Blood-brain Barrier Dysfunction and Post-stroke Seizuresmentioning

confidence: 99%

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Seizures and epilepsy in patients with ischaemic stroke

Zöllner

Schmitt

Rosenow

et al. 2021

Neurol. Res. Pract.

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Background With the increased efficacy of stroke treatments, diagnosis and specific treatment needs of patients with post-stroke seizures (PSS) and post-stroke epilepsy have become increasingly important. PSS can complicate the diagnosis of a stroke and the treatment of stroke patients, and can worsen post-stroke morbidity. This narrative review considers current treatment guidelines, the specifics of antiseizure treatment in stroke patients as well as the state-of-the-art in clinical and imaging research of post-stroke epilepsy. Treatment of PSS needs to consider indications for antiseizure medication treatment as well as individual clinical and social factors. Furthermore, potential interactions between stroke and antiseizure treatments must be carefully considered. The relationship between acute recanalizing stroke therapy (intravenous thrombolysis and mechanical thrombectomy) and the emergence of PSS is currently the subject of an intensive discussion. In the subacute and chronic post-stroke phases, important specific interactions between necessary antiseizure and stroke treatments (anticoagulation, cardiac medication) need to be considered. Among all forms of prevention, primary prevention is currently the most intensively researched. This includes specifically the repurposing of drugs that were not originally developed for antiseizure properties, such as statins. PSS are presently the subject of extensive basic clinical research. Of specific interest are the role of post-stroke excitotoxicity and blood–brain barrier disruption for the emergence of PSS in the acute symptomatic as well as late (> 1 week after the stroke) periods. Current magnetic resonance imaging research focussing on glutamate excitotoxicity as well as diffusion-based estimation of blood–brain barrier integrity aim to elucidate the pathophysiology of seizures after stroke and the principles of epileptogenesis in structural epilepsy in general. These approaches may also reveal new imaging-based biomarkers for prediction of PSS and post-stroke epilepsy. Conclusion PSS require the performance of individual risk assessments, accounting for the potential effectiveness and side effects of antiseizure therapy. The use of intravenous thrombolysis and mechanical thrombectomy is not associated with an increased risk of PSS. Advances in stroke imaging may reveal biomarkers for PSS.

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Section: Blood-brain Barrier Dysfunction and Post-stroke Seizuresmentioning

confidence: 99%

Section: Blood-brain Barrier Dysfunction and Post-stroke Seizuresmentioning

confidence: 99%

Seizures and epilepsy in patients with ischaemic stroke

Zöllner

Schmitt

Rosenow

et al. 2021

Neurol. Res. Pract.

View full text Add to dashboard Cite

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“…This relationship was also seen in a recent large CT perfusion–based study. 49 Another interesting finding that has come out of both CT 37 and MRI 53 studies is that better collateralization is associated with less BBB disruption. This may explain why ICH rates remained low in studies that used penumbral imaging to select patients in an extended time window.…”

Section: Pretreatment Imaging Biomarkers Of Post-evt Ichmentioning

confidence: 99%

Role of Brain Imaging in the Prediction of Intracerebral Hemorrhage Following Endovascular Therapy for Acute Stroke

Seners

Wouters

Maïer

et al. 2023

Stroke

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Currently most acute ischemic stroke patients presenting with a large vessel occlusion are treated with endovascular therapy (EVT), which results in high rates of successful recanalization. Despite this success, more than half of EVT-treated patients are significantly disabled 3 months later partly due to the occurrence of post-EVT intracerebral hemorrhage. Predicting post-EVT intracerebral hemorrhage is important for individualizing treatment strategies in clinical practice (eg, safe initiation of early antithrombotic therapies), as well as in selecting the optimal candidates for clinical trials that aim to reduce this deleterious outcome. Emerging data suggest that brain and vascular imaging biomarkers may be particularly relevant since they provide insights into the ongoing acute stroke pathophysiology. In this review/perspective, we summarize the accumulating literature on the role of cerebrovascular imaging biomarkers in predicting post-EVT–associated intracerebral hemorrhage. We focus on imaging acquired before EVT, during the EVT procedure, and in the early post-EVT time frames when new therapeutic therapies could be tested. Accounting for the complex pathophysiology of post-EVT–associated intracerebral hemorrhage, this review may provide some guidance for future prospective observational or therapeutic studies.

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“…The liposomes are expected to start to degrade once they enter areas of the brain with a raised expression of, e.g., matrix metalloproteinases. This approach does not demand the liposomes to be functionalized by conjugation to a targeting antibody, but the targeting approach could allow for more widespread uptake of the liposomes in the surrounding areas of a central pathology, e.g., in ischemic stroke, the penumbra zone, where the BBB often remains intact [ 80 ]. Targeting to the BECs could enhance the liposomal delivery, which might allow, e.g., enhanced pharmacological preconditioning using focused ultrasound and microbubble treatment [ 81 ].…”

Section: Targeting Nanoparticles To the Brain Endothelium In Patholog...mentioning

confidence: 99%

Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

et al. 2022

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The blood–brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for the delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.

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The Relationship Between Penumbral Tissue and Blood-Brain Barrier Disruption in Acute Stroke Patients Presenting in an Extended Time Window

Cited by 12 publications

References 16 publications

Seizures and epilepsy in patients with ischaemic stroke

Seizures and epilepsy in patients with ischaemic stroke

Role of Brain Imaging in the Prediction of Intracerebral Hemorrhage Following Endovascular Therapy for Acute Stroke

Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

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