Controllable Permeability of Blood-brain Barrier and Reduced Brain Injury Through Low-intensity Pulsed Ultrasound Stimulation

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Oct 31

PMID 26517350

Citations 14

Authors

Wei-Shen Su

Min-Lan Tsai

Sin-Luo Huang

Shing-Hwa Liu

Feng-Yi Yang

Affiliations

Soon will be listed here.

Abstract

It has been shown that the blood-brain barrier (BBB) can be locally disrupted by focused ultrasound (FUS) in the presence of microbubbles (MB) while sustaining little damage to the brain tissue. Thus, the safety issue associated with FUS-induced BBB disruption (BBBD) needs to be investigated for future clinical applications. This study demonstrated the neuroprotective effects induced by low-intensity pulsed ultrasound (LIPUS) against brain injury in the sonicated brain. Rats subjected to a BBB disruption injury received LIPUS exposure for 5 min after FUS/MB application. Measurements of BBB permeability, brain water content, and histological analysis were then carried out to evaluate the effects of LIPUS. The permeability and time window of FUS-induced BBBD can be effectively modulated with LIPUS. LIPUS also significantly reduced brain edema, neuronal death, and apoptosis in the sonicated brain. Our results show that brain injury in the FUS-induced BBBD model could be ameliorated by LIPUS and that LIPUS may be proposed as a novel treatment modality for controllable release of drugs into the brain.

Citing Articles

Blood Brain Barrier-Crossing Delivery of Felodipine Nanodrug Ameliorates Anxiety-Like Behavior and Cognitive Impairment in Alzheimer's Disease.

He X, Peng Y, Huang S, Xiao Z, Li G, Zuo Z Adv Sci (Weinh). 2024; 11(34):e2401731.

PMID: 38981028 PMC: 11425895. DOI: 10.1002/advs.202401731.

Consensus review on strategies to improve delivery across the blood-brain barrier including focused ultrasound.

Piper K, Kumar J, Domino J, Tuchek C, Vogelbaum M Neuro Oncol. 2024; 26(9):1545-1556.

PMID: 38770775 PMC: 11376463. DOI: 10.1093/neuonc/noae087.

Neuroprotection by Abdominal Ultrasound in Lipopolysaccharide-Induced Systemic Inflammation.

Song W, Hung T, Liu S, Zheng Y, Lin H, Yang F Int J Mol Sci. 2023; 24(11).

PMID: 37298275 PMC: 10253353. DOI: 10.3390/ijms24119329.

Ultrasound in Traumatic Spinal Cord Injury: A Wide-Open Field.

Hwang B, Mampre D, Ahmed A, Suk I, Anderson W, Manbachi A Neurosurgery. 2021; 89(3):372-382.

PMID: 34098572 PMC: 8889947. DOI: 10.1093/neuros/nyab177.

Effect of Low Intensity Transcranial Ultrasound (LITUS) on Post-traumatic Brain Edema in Rats: Evaluation by Isotropic 3-Dimensional T2 and Multi-TE T2 Weighted MRI.

Zheng T, Du J, Yuan Y, Wu S, Jin Y, Shi Q Front Neurol. 2020; 11:578638.

PMID: 33281713 PMC: 7689022. DOI: 10.3389/fneur.2020.578638.

References

Feickert H, Drommer S, Heyer R . Severe head injury in children: impact of risk factors on outcome. J Trauma. 1999; 47(1):33-8. DOI: 10.1097/00005373-199907000-00008. View

Zweckberger K, Eros C, Zimmermann R, Kim S, Engel D, Plesnila N . Effect of early and delayed decompressive craniectomy on secondary brain damage after controlled cortical impact in mice. J Neurotrauma. 2006; 23(7):1083-93. DOI: 10.1089/neu.2006.23.1083. View

Zhang X, Chen Y, Jenkins L, Kochanek P, Clark R . Bench-to-bedside review: Apoptosis/programmed cell death triggered by traumatic brain injury. Crit Care. 2005; 9(1):66-75. PMC: 1065095. DOI: 10.1186/cc2950. View

Hynynen K, McDannold N, Vykhodtseva N, Raymond S, Weissleder R, Jolesz F . Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery. J Neurosurg. 2006; 105(3):445-54. DOI: 10.3171/jns.2006.105.3.445. View

Hynynen K, McDannold N, Sheikov N, Jolesz F, Vykhodtseva N . Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage. 2004; 24(1):12-20. DOI: 10.1016/j.neuroimage.2004.06.046. View

McDannold N, Vykhodtseva N, Raymond S, Jolesz F, Hynynen K . MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits. Ultrasound Med Biol. 2005; 31(11):1527-37. DOI: 10.1016/j.ultrasmedbio.2005.07.010. View

Yang F, Chang W, Li J, Wang H, Chen J, Chang C . Pharmacokinetic analysis and uptake of 18F-FBPA-Fr after ultrasound-induced blood-brain barrier disruption for potential enhancement of boron delivery for neutron capture therapy. J Nucl Med. 2014; 55(4):616-21. DOI: 10.2967/jnumed.113.125716. View

Kempski O . Cerebral edema. Semin Nephrol. 2001; 21(3):303-7. DOI: 10.1053/snep.2001.21665. View

Marquet F, Teichert T, Wu S, Tung Y, Downs M, Wang S . Real-time, transcranial monitoring of safe blood-brain barrier opening in non-human primates. PLoS One. 2014; 9(2):e84310. PMC: 3914779. DOI: 10.1371/journal.pone.0084310. View

10.

Donkin J, Vink R . Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol. 2010; 23(3):293-9. DOI: 10.1097/WCO.0b013e328337f451. View

11.

Liu H, Hua M, Chen P, Chu P, Pan C, Yang H . Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. Radiology. 2010; 255(2):415-25. DOI: 10.1148/radiol.10090699. View

12.

Yang F, Wong T, Teng M, Liu R, Lu M, Liang H . Focused ultrasound and interleukin-4 receptor-targeted liposomal doxorubicin for enhanced targeted drug delivery and antitumor effect in glioblastoma multiforme. J Control Release. 2012; 160(3):652-8. DOI: 10.1016/j.jconrel.2012.02.023. View

13.

Hynynen K, McDannold N, Vykhodtseva N, Jolesz F . Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology. 2001; 220(3):640-6. DOI: 10.1148/radiol.2202001804. View

14.

Yang F, Chang W, Chen J, Lee L, Hung Y . Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET. Neuroimage. 2013; 90:93-8. DOI: 10.1016/j.neuroimage.2013.12.033. View

15.

Shapira Y, Setton D, Artru A, Shohami E . Blood-brain barrier permeability, cerebral edema, and neurologic function after closed head injury in rats. Anesth Analg. 1993; 77(1):141-8. DOI: 10.1213/00000539-199307000-00028. View

16.

Reulen H, Graham R, Spatz M, KLATZO I . Role of pressure gradients and bulk flow in dynamics of vasogenic brain edema. J Neurosurg. 1977; 46(1):24-35. DOI: 10.3171/jns.1977.46.1.0024. View

17.

Crisci A, Ferreira A . Low-intensity pulsed ultrasound accelerates the regeneration of the sciatic nerve after neurotomy in rats. Ultrasound Med Biol. 2002; 28(10):1335-41. DOI: 10.1016/s0301-5629(02)00576-8. View

18.

Yang F, Lu W, Lin W, Chang C, Huang S . Enhancement of Neurotrophic Factors in Astrocyte for Neuroprotective Effects in Brain Disorders Using Low-intensity Pulsed Ultrasound Stimulation. Brain Stimul. 2015; 8(3):465-73. DOI: 10.1016/j.brs.2014.11.017. View

19.

Baldwin S, Fugaccia I, Brown D, Brown L, Scheff S . Blood-brain barrier breach following cortical contusion in the rat. J Neurosurg. 1996; 85(3):476-81. DOI: 10.3171/jns.1996.85.3.0476. View

20.

McDannold N, Vykhodtseva N, Hynynen K . Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood-brain barrier disruption. Ultrasound Med Biol. 2008; 34(6):930-7. PMC: 2459318. DOI: 10.1016/j.ultrasmedbio.2007.11.009. View