Emerging paradigms in nanotechnology for imaging and treatment of cerebral ischemia

Kaviarasi, Sathyasivam; Yuba, Eiji; Harada, Atsushi; Krishnan, Uma Maheswari

doi:10.1016/j.jconrel.2019.02.031

Cited by 54 publications

(40 citation statements)

References 195 publications

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“…It is clear that the changes that occurred in CBF and SUVR were more dramatic in the synchronous region than in either the CBF-decreased areas alone or the SUVR-decreased areas alone. Ischaemic cerebrovascular disease is a fatal condition that arises due to insufficient blood flow and metabolic impairment to damages brain cells [43,44]. Theoretically, vascular stenosis or occlusion immediately affected perfusion and causes metabolic changes in the area of the vascular distribution.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous PET-MRI imaging of cerebral blood flow and glucose metabolism in the symptomatic unilateral internal carotid artery/middle cerebral artery steno-occlusive disease

Cui

Zhang

et al. 2019

Eur J Nucl Med Mol Imaging

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Purpose Cerebral blood flow (CBF) and glucose metabolism are important and significant factors in ischaemic cerebrovascular disease. The objective of this study was to use quantitative hybrid PET/MR to evaluate the effects of surgery treatment on the symptomatic unilateral internal carotid artery/middle cerebral artery steno-occlusive disease. Methods Fifteen patients diagnosed with ischaemic cerebrovascular disease were evaluated using a hybrid TOF PET/MR system (Signa, GE Healthcare). The CBF value measured by arterial spin labelling (ASL) and the standardized uptake value ratio (SUVR) measured by 18 F-FDG PET were obtained, except for the infarct area and its contralateral side, before and after bypass surgery. The asymmetry index (AI) was calculated from the CBF and SUVR of the ipsilateral and contralateral cerebral hemispheres, respectively. The ΔCBF and ΔSUVR were calculated as the percent changes of CBF and SUVR between before and after surgery, and paired t tests were used to determine whether a significant change occurred. Spearman's rank correlation was also used to compare CBF with glucose metabolism in the same region. Results The analysis primarily revealed that after bypass surgery, a statistically significant increase occurred in the CBF on the affected side (P < 0.01). The postprocedural SUVR was not significantly higher than the preprocedural SUVR (P > 0.05). However, the postprocedural AI values for CBF and SUVR were significantly lower after surgery than before surgery (P < 0.01). A significant correlation was found between the AI values for preoperative CBF and SUVR on the ipsilateral hemisphere (P < 0.01). Conclusions The present study demonstrates that a combination of ASL and 18 F-FDG PET could be used to simultaneously analyse changes in patients' cerebral haemodynamic patterns and metabolism between before and after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery. This therefore represents an essential tool for the evaluation of critical haemodynamic and metabolic status in patients with symptomatic unilateral ischaemic cerebrovascular disease. Bixiao Cui and Tianhao Zhang contributed equally to this study. This article is part of the Topical Collection on Neurology.

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Section: Discussionmentioning

confidence: 99%

Simultaneous PET-MRI imaging of cerebral blood flow and glucose metabolism in the symptomatic unilateral internal carotid artery/middle cerebral artery steno-occlusive disease

Cui

Zhang

et al. 2019

Eur J Nucl Med Mol Imaging

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“…Most neuroprotectant showed limited effects in treating ischemic stroke for their short half-lives, potential toxicity, poor specificity of distribution, as well as low targeting efficiency to cross the BBB to achieve effective drug accumulation at the aimed lesions. 52 For instance, the half-life of edaravone in vivo is as short as 5.4 min, which seriously hinders the effectiveness of the agent. In addition, biological macromolecules such as superoxide dismutase (SOD) which could efficiently eliminate ROS, and cyclosporine A (CsA) which could inhibit the inflammatory response, have exhibited fine protective effect on damaged neurons.…”

Section: Traditional Treatment Strategiesmentioning

confidence: 99%

Recent advances in nanomedicines for the treatment of ischemic stroke

Li¹,

Sun²

2021

Acta Pharmaceutica Sinica B

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Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the brain. Ischemia would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain, where the ischemic cascade eventually leads to cell death and brain infarction. Extensive researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic stroke. However, traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment efficacy. Nanomedicine provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo , achieve effective drug accumulation at the target site, enhance the therapeutic effect and meanwhile reduce the side effect. In this review, we comprehensively describe the pathophysiology of stroke, traditional treatment strategies and emerging nanomedicines, summarize the barriers and methods for transporting nanomedicine to the lesions, and illustrate the latest progress of nanomedicine in treating ischemic stroke, with a view to providing a new feasible path for the treatment of cerebral ischemia.

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“…In recent years, nanotechnology approaches have demonstrated a promising possibility to improve the pharmacokinetics and biodistribution profile of many drugs. [21,23,24] Some studies have shown that the pH gradients between ischemic and normal tissues are used to achieve targeted release. [25] However, the instability of the local environment and the physiological state of other parts of the body limits the release of drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Although the above pathways are effective in regulating angiogenesis, there are still challenges in drug delivery. [ 21 ] As BBB precludes most drugs from entering the brain, many agents are forced to be administered in an invasive manner. Even though BBB can be compromised after ischemic insults, the extent of damage to the integrity of BBB can often not satisfy adequate drug enrichment for treatment.…”

Section: Introductionmentioning

confidence: 99%

pH‐Sensitive, Cerebral Vasculature‐Targeting Hydroxyethyl Starch Functionalized Nanoparticles for Improved Angiogenesis and Neurological Function Recovery in Ischemic Stroke

Yang

Luo

et al. 2021

Adv Healthcare Materials

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Angiogenesis, an essential restorative process following ischemia, is a promising therapeutic approach to improve neurological deficits. However, overcoming the blood-brain barrier (BBB) and effective drug enrichment are challenges for conventional drug delivery methods, which has limited the development of treatment strategies. Herein, a dual-targeted therapeutic strategy is reported to enable pH-sensitive drug release and allow cerebral ischemia targeting to improve stroke therapeutic efficacy. Targeted delivery is achieved by surface conjugation of Pro-His-Ser-Arg-Asn (PHSRN) peptides, which binds to integrin 5 1 enriched in the cerebral vasculature of ischemic tissue. Subsequently, smoothened agonist (SAG), an activator of sonic hedgehog (Shh) signaling, is coupled to PHSRN-HES by pH-dependent electrostatic adsorption. SAG@PHSRN-HES nanoparticles can sensitively release more SAG in the acidic environment of ischemic brain tissue. More importantly, SAG@PHSRN-HES exerts the synergistic mechanisms of PHSRN and SAG to promote angiogenesis and BBB integrity, thus improving neuroplasticity and neurological function recovery. This study proposes a new approach to improve the delivery of medications in the ischemic brain. Dual-targeted therapeutic strategies have excellent potential to treat patients suffering from cerebral infarction.

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Emerging paradigms in nanotechnology for imaging and treatment of cerebral ischemia

Cited by 54 publications

References 195 publications

Simultaneous PET-MRI imaging of cerebral blood flow and glucose metabolism in the symptomatic unilateral internal carotid artery/middle cerebral artery steno-occlusive disease

Simultaneous PET-MRI imaging of cerebral blood flow and glucose metabolism in the symptomatic unilateral internal carotid artery/middle cerebral artery steno-occlusive disease

Recent advances in nanomedicines for the treatment of ischemic stroke

pH‐Sensitive, Cerebral Vasculature‐Targeting Hydroxyethyl Starch Functionalized Nanoparticles for Improved Angiogenesis and Neurological Function Recovery in Ischemic Stroke

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