Several therapeutic agents for neurological disorders are usually not delivered to the brain owing to the presence of the blood–brain barrier (BBB), a special structure present in the central nervous system (CNS). Focused ultrasound (FUS) combined with microbubbles can reversibly and temporarily open the BBB, enabling the application of various therapeutic agents in patients with neurological disorders.
Authors, Year of Publication | Animal Model |
FUS Parameters | Target Region | Main Results |
---|---|---|---|---|
Xhima (2020) [25] | TgCRND8 mice | CF:1.68 MHz PRF:1 Hz TD:120 s AP: Maintained after decreasing to 25% based on subharmonic emissions |
Basal forebrain | Delivery of D3 (peptidomimetic agonist of TrkA) to the basal forebrain via FUS activated the TrkA-related signaling cascades and increased cholinergic neurotransmission. |
Dubey (2020) [28] |
TgCRND8 mice | CF:1.68 MHz PRF:1 Hz TD:120 s AP: 0.23 MPa (feedback controller) |
Cortex and hippocampus | IVIg-FUS significantly increased neurogenesis. FUS alone and IVIg alone significantly reduced amyloid plaques. IVIg-FUS affects neurogenesis through the downregulation of TNF-α. |
Deng (2021) [48] | APP/PS1 transgenic mice | CF:1 MHz PRF:10 Hz TD:60 s AP:0.6 MPa |
Posterior 3.5 Lateral 3.5 Ventral 3.5 (mm) |
Proved the possibility of extracting exosomes from astrocytes through ultrasonic stimulation. Astrocyte-derived exosome was delivered to the brain after opening the BBB to confirm the amyloid clearance effect. |
Feng (2021) [49] | Sprague-Dawley rats Aβ (1–40) injection model |
CF:1 MHz TD:60 s AP:0.8 MPa |
Hippocampus | As a result of the delivery of MpLXSN-BDNF (modified MB with retrovirus-BDNF) through FUS, cognitive function is improved, and BDNF restores synaptic loss. |
Leinenga (2021) [50] | APP23 transgenic mice | CF:1 MHz PRF:10 Hz TD:6 s AP:0.7 MPa |
Whole brain | The combined treatment of scanning ultrasound and Aducanumab induced the effect of reducing amyloid plaques in the hippocampus and restored cognitive function. |
Poon (2021) [51] | TgCRND8 mice | CF:1 MHz PRF:1 Hz TD:120 s AP:0.28–0.55 MPa |
Hippocampi and cortices | FUS-mediated BBB opening treatment three to five times biweekly did not induce neutrophil recruitment or phagocytosis of amyloid plaques. |
Sun (2021) [52] | Aged APP/PS1dE9 mice | CF:278 kHz PRF:2 Hz TD:100 s AP:0.33 MPa |
Hippocampi | FUS increased the delivery rate of 07/2a mAb (Fc-competent anti-pGlu3 Aβ monoclonal antibody) to the brain by 5.5 times. Co-treatment with FUS and 07/2a mAb induces greater effects on learning and memory recovery and increases synaptic puncta. |
Luo (2022) [53] | Kunming mice Aβ1–42 injection model |
CF:1 MHz PRF:1 Hz TD:120 s Voltage: 200 mV |
Hippocampus | FUS-Gastrodin treatment restored memory and alleviated neuropathology. FUS-Gastrodin reduced Aβ, tau, and P-tau and upregulated BDNF, synaptophysin, and PSD-95 in the hippocampus. |
Bathini (2022) [54] | APP/PS1dE9 transgenic mice | CF:278 kHz PRF:2 Hz TD:100 s AP:0.33 MPa |
Cortex and hippocampus | 07/2a mAb (anti-pyroglutamate-3 Aβ antibody) delivered with FUS resulted in a 5- to 6-fold increase in the brain-to-blood antibody ratio after 4 and 72 h. FUS-07/2a mAb enhanced the immunoreactivity of resident Iba1+ and phagocytic CD68+ microglia. |
Bajracharya (2022) [55] | K3 mice (human 1N4R tau) | CF:1 MHz PRF:10 Hz TD:6 s AP:0.5 MPa |
Whole brain | Repeated FUS-BBB opening reduces tau inclusions. FUS-BBB opening mediates delivery of RNF5 (tau-specific monoclonal antibody) increase brain uptake and accumulates in unclear cells within the pyramidal layer. |
Kong (2022) [42] | 5×FAD mice | CF:0.5 MHz PRF:1 Hz TD:120 s AP:0.25 MPa |
Hippocampi | Combined therapy of FUS and Aducanumab decreases amyloid deposits, increases neurogenesis, and attenuates cognitive function deficits. |
Authors, Year of Publication | Animal Model |
FUS Parameters | Target Region | Main Results |
---|---|---|---|---|
Ji (2019) [72] | C57BL/6 mice MPTP |
CF:1.5 MHz PRF:10 Hz TD:60 s AP:0.45 MPa |
Striatum and substantia nigra | FUS-Intranasal delivery increased TH immunoreactivity and improved motor control function. |
Lin (2020) [73] |
Balb/c mice MPTP |
CF:1 MHz PRF:10 Hz TD:180 s Voltage:85 V |
Substantia nigra | BDNF or GDNF gene delivery through the UTMD system induces a neuroprotective effect. However, combined with the GDNF/BDNF gene delivery it did not produce benefits compared with individually delivering BDNF or GDNF genes. |
Yan (2021) [74] | C57BL6 mice MPTP |
CF:1 MHz PRF:1 Hz TD:60 s AP:0.24–0.45 MPa |
Cortex, striatum, and substantia nigra | Improves therapeutic efficacy by increasing the delivery rate of encapsulated curcumin through FUS. |
Yuhong (2022) [75] | C57BL/6J mice MPTP |
CF:1 MHz PRF:1 Hz TD:60 s Voltage:100, 150, 200 mV |
Striatum | FUS increased the delivery rate of gastrodin, which induces neuroprotective effects, by 1.8-fold. FUS-Gastrodin treatment increased the expression levels of Bcl-2, BDNF, PSD-95, and synaptophysin protein and decreased the levels of caspase-3 in the striatum. |
Trinh (2022) [76] | Sprague-Dawley rats | CF:1 MHz PRF:1 Hz TD:120 s AP:0.4 MPa |
Striatum and substantia nigra | FUS-induced BBB permeability in the striatum and substantia nigra. SIRT3-myc (viral vector gene therapies for PD) was expressed only in the striatum. |
Authors, Year of Publication | Animal Model |
FUS Parameters | Target Region | Main Results |
---|---|---|---|---|
McDannold (2020) [96] | Sprague-Dawley rats F98 glioma |
CF:230 kHz PRF:1.1 Hz TD:55 s AP:119–186 kPa |
Striatum (Tumor) |
It was confirmed that the ExAblate Neuro low-frequency clinical TcMRgFUS system could stably open the BBB in a rat model. Although delivery of irinotecan to the brain was not neurotoxic, it was not effective in prolonging survival or reducing the growth of gliomas. |
Curley (2020) [93] | athymic nude mice U87 GBM |
CF:1.1 MHz DC:0.5% TD:120 s AP:0.45–0.55 MPa |
Striatum (Tumor) |
Interstitial fluid transport in brain tumors is increased by FUS. FUS increased the dispersion of directly injected brain-penetrating nanoparticles through tumor tissue by >100%. |
Englander (2021) [97] | B6 mice PDGF-B + PTEN−/−p53−/− murine glioma |
CF:1.5 MHz PRF:5 Hz TD:120 s AP:0.7 MPa |
Pons (Tumor) |
FUS increased the delivery rate of etoposide into the tumor site more than five times compared to the control group, but there was no difference in survival rate or inflammation. |
Sheybani (2021) [98] | C57BL/6 mice GL261 glioma |
CF:1.1 MHz DC:0.5% TD:120 s AP:0.4 MPa |
Striatum (Tumor) |
[89Zr]-mCD47 (phagocytic immunotherapy) delivery with repeated FUS can significantly constrain tumor outgrowth and extend survival rate. |
Ye (2021) [99] | Swiss-Webster mice GL261 glioma |
CF:1.5 MHz PRF:5 Hz TD:60 s AP:0.43 MPa |
Brain stem (Tumor) |
FUS-mediated intranasal delivery increased the delivery rate of anti-PD-L1 antibodies to the brain stem by 4.03-fold. |
Chen (2021) [100] | Fisher rats C6 glioma |
CF:400 kHz PRF:1 Hz TD:120 s AP:0.81 MPa |
Caudate putamen (Tumor) |
CD4+ (helper TILs) and CD8+ (cytotoxic TILs) immunogenic responses were significantly increased after 7 days of FUS treatment. |
Moon (2022) [101] | BALB/c nude mice U87 GBM |
CF:1 MHz PRF:1 Hz TD:60 s AP:1 W/cm2 |
Cerebral hemisphere | Sonosensitive liposome-encapsulating doxorubicin enhances permeability by FUS-mediated BBB opening. The GBM cytotoxicity of IMP301-DC was significantly increased. |
Sheybani (2022) [102] | C57BL/6 mice GL261 glioma |
CF:1.1 MHz PRF:1 Hz TD:120 s AP:0.4–0.6 MPa |
Striatum (Tumor) |
FUS-mediated BBB opening in gliomas transiently induces inflammatory effects. |
This entry is adapted from the peer-reviewed paper 10.3390/neurolint15010018