Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (5): 1000-1005. doi: 10.19723/j.issn.1671-167X.2022.05.029

Previous Articles     Next Articles

Epidural photobiomodulation accelerates the drainage of brain interstitial fluid and its mechanism

Ying CAI1,2,Qiao-qin WAN2,*(),Xian-jie CAI3,4,Ya-juan GAO1,5,Hong-bin HAN1,3,6,*()   

  1. 1. Department of Radiology, Peking University Third Hospital, Beijing 100191, China
    2. Peking University School of Nursing, Beijing 100191, China
    3. Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China
    4. Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China
    5. NMPA Key Laboratory for Evaluation of Medical Imaging Equipment and Technique, Beijing 100191, China
    6. Peking University Shenzhen Graduate School, Shenzhen 518055, China
  • Received:2022-03-22 Online:2022-10-18 Published:2022-10-14
  • Contact: Qiao-qin WAN,Hong-bin HAN E-mail:qqwan05@163.com;hanhongbin@bjmu.edu.cn
  • Supported by:
    the National Nature Science Foundation(61827808);the National Nature Science Foundation(12126601);the Shenzhen Science and Technology Program(KQTD20180412181221912)

RICH HTML

   

PDF (PC)

Abstract:

Objective: To evaluate the effect of photobiomodulation (PBM) on the drainage of brain interstitial fluid (ISF) and to investigate the possible mechanism of the positive effect of PBM on Alzheimer's disease (AD). Methods: Twenty-four SD male rats were randomly divided into PBM group (n=12), sham PBM group (n=6), and negative control group (n=6). According to the injection site of tracer, the PBM group was further divided into PBM-ipsilateral traced group (n=6) and PBM-contralateral traced group (n=6). Rats in the PBM group and the sham PBM group were exposed to the dura minimally invasively on the skull corresponding to the frontal cortical area reached by ISF drainage from caudate nucleus region. The PBM group was irradiated by using 630 nm red light (5-6 mW/cm2), following an irradiation of 5 min with a 2 min pause, and a total of 5 times; the sham PBM group was kept in the same position for the same time using the light without power. The negative control group was kept without any measure. After PBM, tracer was injected into caudate nucleus of each group. The changes of ISF drainage in caudate nucleus were observed according to the diffusion and distribution of tracer molecule by tracer-based magnetic resonance imaging, and the structural changes of brain extracellular space (ECS) were analyzed by diffusion rate in ECS-mapping (DECS-mapping) technique. Finally, parameters reflecting the structure of brain ECS and the drainage of ISF were obtained: volume fraction (α), tortuo-sity (λ), half-life (T1/2), and DECS. The differences of parameters among different groups were compared to analyze the effect of PBM on brain ECS and ISF. One-Way ANOVA post hoc tests and independent sample t test were used for statistical analysis. Results: The parameters including T1/2, DECS, and λ were significantly different among the PBM-ipsilateral traced group, the PBM-contralateral traced group, and the sham PBM group (F=79.286, P < 0.001; F=13.458, P < 0.001; F=10.948, P=0.001), while there was no difference in the parameter α of brain ECS among the three groups (F=1.217, P=0.324). Compared with the sham PBM group and the PBM-contralateral traced group, the PBM-ipsilateral traced group had a significant decrease in the parameter T1/2 [(45.45±6.76) min vs. (76.01±3.44) min, P < 0.001; (45.45±6.76) min vs. (78.07±4.27) min, P < 0.001], representing a significant acceleration of ISF drainage; the PBM-ipsilateral traced group had a significant increase in the parameter DECS [(4.51±0.77)×10-4 mm2/s vs. (3.15±0.44)×10-4 mm2/s, P < 0.001; (4.51±0.77)×10-4 mm2/s vs. (3.01±0.38)×10-4 mm2/s, P < 0.001], representing a significantly increased molecular diffusion rate of in the brain ECS; the PBM-ipsilateral traced group had a significant decrease in the parameter λ (1.51±0.21 vs. 1.85±0.12, P=0.001; 1.51±0.21 vs. 1.89±0.11, P=0.001), representing a significant decrease in the degree of tortuosity in the brain ECS. Conclusion: PBM can regulate the brain ISF drainage actively, which may be one of the potential mechanisms of the effect of PBM therapy on AD. This study provides a new method for enhancing the brain function via ECS pathway.

Key words: Extracellular fluid, Photobiomodulation, Alzheimer's disease, Radioactive tracers, Magnetic resonance imaging

CLC Number: 

  • R749.1

Figure 1

Diffusion and distribution of tracer over time in caudate nucleus of rats in different groups Cor, coronal position; Axi, axial position; Sag, sagittal position; PBM, photobiomodulation. A, PBM-ipsilateral traced group; B, PBM-contralateral traced group; C, sham PBM group; D, negative control group."

Table 1

Brain ECS parameters in caudate nucleus of rats in each group ($\bar x \pm s$, n=6)"

Group T1/2/min DECS/(×10-4 mm2/s) α/% λ
Negative control 73.35±4.48 3.31±0.07 16.48±0.30 1.80±0.02
PBM-ipsilateral traced 45.45±6.76 4.51±0.77 16.61±0.48 1.51±0.21
PBM-contralateral traced 78.07±4.27* 3.01±0.38* 16.30±0.52 1.89±0.11*
Sham PBM 76.01±3.44* 3.15±0.44* 16.24±0.25 1.85±0.12*
Fa 79.286 13.458 1.217 10.948
Pa < 0.001 < 0.001 0.324 0.001

Figure 2

Two-dimensional and three-dimensional DECS-maps in caudate nucleus of rats in different groups The two-dimensional DECS map showed that the maximum diffusion rate of molecular in the PBM-ipsilateral traced group (A) was higher than that in the PBM-contralateral traced group (B), and the sham PBM group (C).The three-dimensional DECS map showed that the maximum diffusion rate of mole-cular in the PBM-ipsilateral traced group (D) was higher than that in the PBM-contralateral traced group (E), and the sham PBM group (F). PBM, photobiomodulation."

1 Lei Y , Han H , Yuan F , et al. The brain interstitial system: Ana-tomy, modeling, in vivo measurement, and applications[J]. Prog Neurobiol, 2017, 157, 230- 246.
doi: 10.1016/j.pneurobio.2015.12.007
2 De Strooper B , Karran E . The cellular phase of Alzheimer's di-sease[J]. Cell, 2016, 164 (4): 603- 615.
doi: 10.1016/j.cell.2015.12.056
3 Feng W , Zhang Y , Wang Z , et al. Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer's disease mouse model with suppression of glymphatic clearance[J]. Alzheimers Res Ther, 2020, 12 (1): 125.
doi: 10.1186/s13195-020-00688-1
4 Tao L , Liu Q , Zhang F , et al. Microglia modulation with 1 070-nm light attenuates Aβ burden and cognitive impairment in Alzheimer's disease mouse model[J]. Light Sci Appl, 2021, 10 (1): 179.
doi: 10.1038/s41377-021-00617-3
5 Yue X , Mei Y , Zhang Y , et al. New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice[J]. Alzheimers Dement (NY), 2019, 5, 671- 684.
doi: 10.1016/j.trci.2019.09.007
6 Iliff J J , Wang M , Zeppenfeld DM , et al. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain[J]. J Neurosci, 2013, 33 (46): 18190- 18199.
doi: 10.1523/JNEUROSCI.1592-13.2013
7 Hong N . Photobiomodulation as a treatment for neurodegenerative disorders: Current and future trends[J]. Biomed Eng Lett, 2019, 9 (3): 359- 366.
doi: 10.1007/s13534-019-00115-x
8 Lu Y , Wang R , Dong Y , et al. Low-level laser therapy for beta amyloid toxicity in rat hippocampus[J]. Neurobiol Aging, 2017, 49, 165- 182.
doi: 10.1016/j.neurobiolaging.2016.10.003
9 da Luz Eltchechem C , Salgado ASI , Zangaro RA , et al. Transcranial LED therapy on amyloid-beta toxin 25-35 in the hippocampal region of rats[J]. Lasers Med Sci, 2017, 32 (4): 749- 756.
doi: 10.1007/s10103-017-2156-3
10 Berman MH , Halper JP , Nichols TW , et al. Photobiomodulation with near infrared light helmet in a pilot, placebo controlled clinical trial in dementia patients testing memory and cognition[J]. J Neurol Neurosci, 2017, 8 (1): 176.
11 Chan AS , Lee TL , Yeung MK , et al. Photobiomodulation improves the frontal cognitive function of older adults[J]. Int J Geriatr Psychiatry, 2019, 34 (2): 369- 377.
doi: 10.1002/gps.5039
12 Hamblin MR . Photobiomodulation for Alzheimer's disease: Has the light dawned?[J]. Photonics, 2019, 6 (3): 77.
doi: 10.3390/photonics6030077
13 Ye Y , Li Y , Fang F . Opening of brain blood barrier induced by red light and central analgesic improvement of cobra neurotoxin[J]. J Photochem Photobiol B, 2014, 134, 16- 22.
doi: 10.1016/j.jphotobiol.2014.03.019
14 Semyachkina-Glushkovskaya O , Abdurashitov A , Dubrovsky A , et al. Photobiomodulation of lymphatic drainage and clearance: Perspective strategy for augmentation of meningeal lymphatic functions[J]. Biomed Opt Express, 2020, 11 (2): 725- 734.
doi: 10.1364/BOE.383390
15 Han H , Shi C , Fu Y , et al. A novel MRI tracer-based method for measuring water diffusion in the extracellular space of the rat brain[J]. IEEE J Biomed Health Inform, 2014, 18 (3): 978- 983.
doi: 10.1109/JBHI.2014.2308279
16 Rojas JC , Gonzalez-Lima F . Neurological and psychological applications of transcranial lasers and LEDs[J]. Biochem Pharmacol, 2013, 86 (4): 447- 457.
doi: 10.1016/j.bcp.2013.06.012
17 Pitzschke A , Lovisa B , Seydoux O , et al. Red and NIR light dosimetry in the human deep brain[J]. Phys Med Biol, 2015, 60 (7): 2921- 2937.
doi: 10.1088/0031-9155/60/7/2921
18 Wang A , Wang R , Cui D , et al. The drainage of interstitial fluid in the deep brain is controlled by the integrity of myelination[J]. Aging Dis, 2019, 10 (5): 937- 948.
doi: 10.14336/AD.2018.1206
19 Iliff JJ , Wang M , Liao Y , et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β[J]. Sci Transl Med, 2012, 4 (147): 147ra111.
20 Louveau A , Smirnov I , Keyes TJ , et al. Structural and functional features of central nervous system lymphatic vessels[J]. Nature, 2015, 523 (7560): 337- 341.
doi: 10.1038/nature14432
21 Charriaut-Marlangue C , Bonnin P , Pham H , et al. Nitric oxide signaling in the brain: A new target for inhaled nitric oxide?[J]. Ann Neurol, 2013, 73 (4): 442- 448.
doi: 10.1002/ana.23842
22 Sykova E , Nicholson C . Diffusion in brain extracellular space[J]. Physiol Rev, 2008, 88 (4): 1277- 1340.
doi: 10.1152/physrev.00027.2007
23 Tong Z , Han C , Luo W , et al. Accumulated hippocampal formaldehyde induces age-dependent memory decline[J]. Age (Dordr), 2013, 35 (3): 583- 596.
doi: 10.1007/s11357-012-9388-8
24 Zhu R , Zhang G , Jing M , et al. Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction[J]. Nat Commun, 2021, 12 (1): 581.
doi: 10.1038/s41467-020-20754-4
25 韩鸿宾. 细胞微环境成像新方法与脑分区稳态的发现[J]. 武警医学, 2016, 27 (4): 325- 328.
26 Lilja-Cyron A , Andresen M , Kelsen J , et al. Long-term effect of decompressive craniectomy on intracranial pressure and possible implications for intracranial fluid movements[J]. Neurosurgery, 2020, 86 (2): 231- 240.
doi: 10.1093/neuros/nyz049
[1] Yuxuan TIAN,Mingjian RUAN,Yi LIU,Derun LI,Jingyun WU,Qi SHEN,Yu FAN,Jie JIN. Predictive effect of the dual-parametric MRI modified maximum diameter of the lesions with PI-RADS 4 and 5 on the clinically significant prostate cancer [J]. Journal of Peking University (Health Sciences), 2024, 56(4): 567-574.
[2] Yi LIU,Chang-wei YUAN,Jing-yun WU,Qi SHEN,Jiang-xi XIAO,Zheng ZHAO,Xiao-ying WANG,Xue-song LI,Zhi-song HE,Li-qun ZHOU. Diagnostic efficacy of prostate cancer using targeted biopsy with 6-core systematic biopsy for patients with PI-RADS 5 [J]. Journal of Peking University (Health Sciences), 2023, 55(5): 812-817.
[3] Chang-wei YUAN,De-run LI,Zhi-hua LI,Yi LIU,Gang-zhi SHAN,Xue-song LI,Li-qun ZHOU. Application of dynamic contrast enhanced status in multiparametric magnetic resonance imaging for prostatic cancer with PI-RADS 4 lesion [J]. Journal of Peking University (Health Sciences), 2023, 55(5): 838-842.
[4] Ying LIU,Ran HUO,Hui-min XU,Zheng WANG,Tao WANG,Hui-shu YUAN. Correlations between plaque characteristics and cerebral blood flow in patients with moderate to severe carotid stenosis using magnetic resonance vessel wall imaging [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 646-651.
[5] Qiang FU,Guan-ying GAO,Yan XU,Zhuo-hua LIN,You-jing SUN,Li-gang CUI. Comparative study of ultrasound and magnetic resonance imaging in the diagnosis of asymptomatic anterosuperior acetabular labrum tears [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 665-669.
[6] Shan YE,Ping-ping JIN,Nan ZHANG,Hai-bo WU,Lin SHI,Qiang ZHAO,Kun YANG,Hui-shu YUAN,Dong-sheng FAN. Cortical thickness and cognitive impairment in patients with amyotrophic lateral sclerosis [J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1158-1162.
[7] WANG Shu-lei,GAO Yang-xu,ZHANG Hong-wu,YANG Hai-bo,LI Hui,LI Yu,SHEN Li-xue,YAO Hong-xin. Clinical analysis of 30 cases of basal ganglia germinoma in children [J]. Journal of Peking University (Health Sciences), 2022, 54(2): 222-226.
[8] ZHANG Fan,CHEN Qu,HAO Yi-chang,YAN Ye,LIU Cheng,HUANG Yi,MA Lu-lin. Relationship between recovery of urinary continence after laparoscopic radical prostatectomy and preoperative/postoperative membranous urethral length [J]. Journal of Peking University (Health Sciences), 2022, 54(2): 299-303.
[9] Yi-fan WU,Xiao-yuan ZHANG,Shuang REN,Ying-xiang YU,Cui-qing CHANG. Measurement and evaluation of the quadriceps muscle mass in young men based on magnetic resonance imaging [J]. Journal of Peking University (Health Sciences), 2021, 53(5): 843-849.
[10] Hui SHENG,Lei LIANG,Tong-liang ZHOU,Yan-xing JIA,Tong WANG,Lan YUAN,Hong-bin HAN. Improved synthesis process of optical-magnetic bimodal probe of Gd-[4,7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1,4,7,10-tetraaza-cyclododec-1-yl]-acetic acid complexes [J]. Journal of Peking University (Health Sciences), 2020, 52(5): 959-963.
[11] Shi-ming ZHAO,Tie-jun YANG,Chun-miao XU,Xiao-feng GUO,Yong-kang MA,Xue-jun CHEN,Xiang LI,Chao-hong HE. Bladder cancer local staging about muscle invasion: 3.0T MRI performance following transurethral resection [J]. Journal of Peking University (Health Sciences), 2020, 52(4): 701-704.
[12] Yu SONG,Hong-bin HAN,Jun YANG,Ai-bo WANG,Qing-yuan HE,Yuan-yuan LI,Guo-mei ZHAO,Ya-juan GAO,Rui WANG,Yi-xing HAN,Ai-lian LIU,Qing-wei SONG. Effect of convection enhanced delivery on the microstructure of brain extracellular space in aged rats [J]. Journal of Peking University (Health Sciences), 2020, 52(2): 362-367.
[13] Li XU,Ming-jie HU,Yu-yu LI,Hong-dang QU,Wei-dong QIAN,Xiao-lin LIU. Superficial siderosis of the central nervous system caused by myxopapillary ependymoma of conus medullaris and cauda equine: a case report and literature review [J]. Journal of Peking University(Health Sciences), 2019, 51(4): 769-774.
[14] Jing-yun WU,Yue MI,Shui LIU,Lin YAO,Qi TANG,Zhi-song HE,Xiao-ying WANG. Evaluating inferior vena cava wall invasion in renal cell carcinoma tumor thrombus with MRI [J]. Journal of Peking University(Health Sciences), 2019, 51(4): 673-677.
[15] Hong-bin HAN. Discovery of a new division system in brain and the regionalized drainage route of brain interstitial fluid [J]. Journal of Peking University(Health Sciences), 2019, 51(3): 397-401.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd