Table 1.

Studies provide insights into music/sound and rodents’ meningeal lymphatic/glymphatic system. Overview of all studies that showcase the effect of music on the glymphatic system. Each study is broken down based on the overall purpose and the selected sample, design, and study outcomes.

Reference	Test Subjects	Research Methodology	Anatomical/Functional Outcomes
[25] Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.	Disease Condition: None Species: Mouse Strain: BALB/c (Charles River, Italy) Weight: 30 g Avg. Age: 40 day N: 20	Mice were exposed to slow rhythmic music for 6 h for 21 d. Music had mild sound pressure levels, around 50–60 dB. Control mice were placed in a similar environment but without music. Animals had free access to food and water and were placed on a 12 h light/dark schedule. The music was played during nighttime hours due to the mice being nocturnal. On day 22, mice were sacrificed, and the hypothalamus was extracted to measure BDNF and NGF production levels. Sound: Slow rhythm music (~50 and 60 dB)	Compared to the control mice, the music-exposed mice had significantly increased (32 vs. 55 ng/g, p < 0.01) BDNF production in the hypothalamus. Music also had a significant effect (49 vs. 30 ng/g, p < 0.05) on NGF production, but NGF levels conflicted with BDNF changes. In the music-exposed mice, NGF levels were less than those of the control mice.
[26] Music therapy alleviates motor dysfunction in rats with focal cerebral ischemia-reperfusion injury by regulating BDNF expression.	Disease Condition: Focal cerebral ischemia-reperfusion injury Species: Rat Strain: Sprague-Dawley (Nantong, China) Weight: 220–250 g N: 90 Sex: M	Rats underwent middle cerebral artery occlusion (MCAO) for 1h followed by reperfusion. Rats that survived were separated into 4 groups: MCAO 1 h/d 12 h/d Accelerated music group with music for 2 wks Nissl staining was performed on infarct zones and the motor cortex and immunofluorescence BDNF and GFAP. Sound: Mozart K.448 (65–75 dB)	In comparison to the MCAO and 1 h group, data indicated that the motor function in the 12 h/d music group was significantly enhanced. Music therapy notably lowered the focal neurological deficits in the 12 h music group 14 d and 21 d post-MCAO (p < 0.001). On days 14 and 21, the mNSS of the 12 h music group was less than the 1 h music group (p < 0.05). Immunofluorescence assay revealed BDNF accumulation in newborn and astrocyte cells in the music group, and GFAP fluorescence showed substantial intensity in the music group compared to the MCAO group.
[19] Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessel during the opening of blood–brain barrier: mechanisms of brain clearing.	Disease condition: None Species: Mouse Strain: N/D Weight: 25 g N: 89 Sex: M	Evans Blue and FITC-Dextran were used to monitor large and small molecule intravasation through the BBB, respectively. Analyses of Evans Blue were performed in 4 groups: before sound (control) 1, 4, 24 h after sound exposure FITCD extravasation was measured with imaging results only; no statistical differences were reported. First, the audible sound was administered for 60 s, followed by a 60 s pause for 2 h. Then 1 h after sound exposure, FITCD was administered and circulated for 20 min, and then the mouse anatomies were analyzed. Sound: Audible sound (100 dB, 370 Hz)	After 1 h of sound exposure, leakage of Evans Blue dye through the BBB had a 19.7-fold increase compared to the control group (7.30 ± 0.09 vs. 0.37 ± 0.02 μg/g of tissue, p < 0.05). In addition, after 1 h of sound exposure, the meningeal lymphatic vessels increased in diameter by (3.00 ± 0.01 vs. 10.00 ± 0.07 μm, p < 0.05). 4 h and 24 h after sound, BBB permeability recovered to normal conditions, EB extravasation decreased (0.54 ± 0.01 μg/g of tissue), and the BBB was impermeable to FITCD. FITCD extravasation through the BBB and accumulation in the perivascular space, including clearance, occurred within 30 min.
[27] Laser speckle imaging and wavelet analysis of cerebral blood flow associated with the opening of the blood-brain barrier by sound.	Disease Condition: None Species: Mouse Strain: N/D Weight: 20–25 g Avg. Age: 2 mo N: 40 Sex: M	Analyses of BBB permeability were conducted in 4 groups: no music 90 min after sound exposure 4 h after sound exposure 24 h after sound exposure Each group included 10 mice. To trigger the BBB opening, the audible sound was applied in 60 s on/60 s off intervals for 2 h. Then, EB was administered and circulated in the blood for 30 min; FITCD was administered and circulated for 2 min. Afterward, mice were sacrificed, and tissues were analyzed. Sound: Audible sound (110 dB, 370 Hz)	After 90 min of sound, leakage of EB in the BBB increased 23.3 fold compared to the control group (9.10 ± 0.33 vs. 0.39 ± 0.01 μg/g of tissue, p < 0.05). The measure of CBF increased by 51% for 90 min for cerebral veins compared with the control and only by 13% for microvessels compared with the control. Within 4 h of sound, BBB disruption was reversed to normal conditions. FITCD was used alongside Evans Blue as a characterization method to represent higher weight molecules; no statistical data were collected, just imaging. Results indicated sound at a certain degree of frequency and intensity could allow the BBB to open. EB and FITCD markers showed increased leakage and permeability into the BBB after 90 min upon sound exposure (p < 0.05).
[20] Loud music and specific sound stress open BBB.	Disease Condition: None Species: Mouse and Rat Strain: Mongrel and Wistar Weight: 20–25 g Avg. Age: “Wistar male rats of corresponding age been used.” N: 60 Sex: M	4 groups: control 1 h after sound exposure 4 h after sound exposure 24 h after sound exposure Music exposure for 2 h with 60 s on/off intervals ranging from 90–100 db. EB was used to measure the leakage of the BBB. The leakage of tracers was determined in 2 main groups (music and sound) divided into 4 subgroups. Music frequencies were 11–10,000 Hz, and the sound was 370 Hz. The focus was more on the effect of epinephrine and its impact on the BBB. Mongrel mice used are defined as wild mice with no known origin, thus known as “mongrel.” Sound: The music played was “Still Loving You” by Scorpions.	Data indicated music-/sound-induced an increase in BBB permeability based on EB, FITCD, and Gd-DTPA markers. After 1 h of sound exposure, leakage of EB increased 17.3 fold (music) and 18.6 fold (sound) (p < 0.001). Similar results for 90 db, and no change for 70 dB. Optimal time of BBB permeability 1 h after music/sound exposure (100 dB). Natural factors, including loud sounds and music, reversibly open the BBB for high-/low-weight molecules and 100-nm liposomes. However, the opening was short, followed by a quick recovery. Results relating to epinephrine showed an increase of CBF by 19 ± 2% (11.00 ± 0.60 vs. 9.20 ± 0.70 A.U., p < 0.05) in the control group (before sound exposure), This increase led to vasoconstriction and an increase of vascular tone.
[28] Phenomenon of music-induced opening of the blood–brain barrier in healthy mice.	Disease Condition: None Species: Mouse Strain: Mongrel Weight: 20–25 g N: 50 Sex: M	4 groups: control no music exposure, 1 h after music exposure 4 h & 24 h after music exposure Mice exposed to music for 2 h with 60 s on/off intervals ranging from 90–100 dB. Exposed to biomarkers Gd-DTPA, FITCD, and EB under in vivo and ex vivo imaging to measure extravasation of BBB based on music exposure. Mongrel mice used are defined as wild mice with no known origin, thus known as “mongrel.” Sound: The music played was “Still Loving You” by Scorpions. The control group of mice (n = 15) was not exposed to the song or music.	Data indicated that there was clear extravasation of the music-induced opening in the BBB in 11 brain regions. Fluorescent microscopy of Evans Blue showed a visible permeability to the marker in the cerebral microvessels. Statistical data concluded (0.80 ± 0.03 vs. 0.58 ± 0.01 A.U., p < 0.001) extravasation for the cerebral microvessels. FITCD also showed enlargement of lymphatic vessels upon opening of the BBB. Statistical results indicated enlarged lymphatic vessels of deep cervical lymph nodes (22.30 ± 1.50 vs. 37.30 ± 2.00 µm, p < 0.001). The loud sound caused up to a 3.1-fold increase in the plasma level of epinephrine (immediately after the music) vs. the normal state (9.00 ± 1.50 vs. 2.90 ± 0.70 ng/mL, p < 0.001).
[29] A novel method to stimulate lymphatic clearance of beta-amyloid from mouse brain using non-invasive music-induced opening of the blood-brain barrier with EEG markers.	Disease Condition: None Species: Mouse Strain: Mongrel Weight: 20–25 g N: 74 Sex: M	8 groups: control intact BBB mice with EB and Fαβ music-induced opening BBB mice for EB and FITCD mice with the opening of BBB and Fαβ mice with intact BBB and Fαβ Mice were exposed to music for 2 h with 60 s on/off intervals ranging from 0–130 dB. Exposed to biomarkers: Fαβ, FITCD, and EB under in vivo and ex vivo imaging to measure extravasation of BBB based on music exposure. EEG markers were also used to monitor extravasation. Mongrel mice used are defined as wild mice with no known origin, thus known as “mongrel.” Sound: The music played was “Still Loving You” by Scorpions.	Results show extravasation of OBB 1 h after music exposure based on EB in the brain parenchyma (2.84 ± 0.14 µg/g tissue vs. 0.12 ± 0.05 µg/g tissue, p < 0.001). Music exposed mice showed faster extravasation of Fαβ from portions of the brain compared to the intact BBB mice. Faβ was 3.5 fold higher based on the dorsal to ventral part of the brain. (0.11 ± 0.03 a.u. vs. 0.25 ± 0.03 a.u., p < 0.001) (0.42 ± 0.01 a.u. vs. 0.12 ± 0.02 a.u., p < 0.001) They concluded that the use of EEG markers allowed and has practical use in identifying the opening of BBB.