Content uploaded by Min-Ho Nam
Author content
All content in this area was uploaded by Min-Ho Nam on Mar 07, 2019
Content may be subject to copyright.
Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
This article appeared in a journal published by Elsevier. The attached
copy is furnished to the author for internal non-commercial research
and education use, including for instruction at the authors institution
and sharing with colleagues.
Other uses, including reproduction and distribution, or selling or
licensing copies, or posting to personal, institutional or third party
websites are prohibited.
In most cases authors are permitted to post their version of the
article (e.g. in Word or Tex form) to their personal website or
institutional repository. Authors requiring further information
regarding Elsevier’s archiving and manuscript policies are
encouraged to visit:
http://www.elsevier.com/copyright
Author's personal copy
-
REVIEW ARTICLE
-
Adult Neurogenesis and Acupuncture Stimulation at
ST36
Min-Ho Nam
1,3
, Chang Shik Yin
2
, Kwang-Sup Soh
3
, Seung-hoon Choi
1,
*
1
Department of Pathology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
2
Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University,
Seoul, Republic of Korea
3
Nano Primo Research Center, Advanced Institute of Convergence Technology, Seoul National University,
Suwon-si, Gyeonggi-do, Republic of Korea
Received: May 25, 2011
Accepted: Jun 21, 2011
KEYWORDS
acupuncture;
adult neurogenesis;
primo vascular system;
ST36
Abstract
Although it was believed that the brain was incapable of regeneration after embryonic
development, neurogenesis is now known to occur into adulthood. Adult neurogenesis
has been demonstrated in the subventricular zone of the lateral ventricles and the sub-
granular zone of the dentate gyrus of the hippocampus. Acupuncture has long been used
to treat neurologic conditions, and recent reports suggest that neurogenesis may account
for its beneficial effects. ST36 was the most often used acupoint in previous reports and
was shown to enhance cell proliferation and neuronal differentiation. This acupoint may
be linked to the brain through the primo vascular system, an anatomic structure thought
to correspond to acupuncture meridians. This primitive vascular-like system appears to
be involved in physiologic and pathologic processes by circulating substances throughout
the body. The role of the primo vascular system as the link between the skin and brain
underlying the beneficial effects of acupuncture requires further investigation.
1. Introduction
Neurogenesis was traditionally thought to occur primarily
during embryonic development, and neuron loss in adult-
hood due to injury, disease, and aging was considered
permanent. Although neurogenesis is now known to
continue into the postnatal period [1], a decline in neuro-
genesis and regenerative capacity of the nervous system
contributes to age-related impairment [2]. Since the first
study demonstrating neurogenesis in the adult mammalian
brain was published in 1965 [3], research has focused on the
involvement of neural stem cells [4] and neurogenesis-
regulating factors [5] in this process. There is evidence to
suggest that neurogenesis is altered in individuals experi-
encing cognitive decline and neurodegenerative disorders
[6]. Although acupuncture has been widely used for
neurologic disorders in the East, its effectiveness for
treating stroke [7] and Alzheimer’s disease [8,9] remains
unclear. A recent study demonstrated that acupuncture
induces cell differentiation and neuroblast differentiation
* Corresponding author: Seung-hoon Choi, Department of Pathology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong,
Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
E-mail: choish@khu.ac.kr (S.-h. Choi).
ª2011 Korean Pharmacopuncture Institute
doi:10.1016/j.jams.2011.09.001
J Acupunct Meridian Stud 2011;4(3):153e158
J Acupunct Meridian Stud 2011;4(3):153e158
Author's personal copy
in the rat hippocampus [10], providing evidence for its
utility as a neurogenesis-stimulating therapy. In this review,
we provide an overview of neurogenesis and acupuncture,
and discuss this topic in relation to the primo vascular
system (PVS), a proposed anatomic structure corresponding
to acupuncture meridians [11,12].
2. Adult Neurogenesis in Mammals
Adult neural stem cells can self-renew and differentiate
into all the major types of neural cells of the adult nervous
system, including neurons, astrocytes, and oligodendro-
cytes (Fig. 1)[13]. Because the stem cell properties of adult
neural stem cells were shown in vitro, but were not
demonstrated convincingly in vivo until recently, the term
“neural progenitors” is used to describe all dividing cells
with some capacity for differentiation [14].
The first study on adult neurogenesis, published in 1965,
used 3H-thymidine autoradiography to detect neuronal
proliferation in young adult rats [3]. These new cells
exhibited morphologic characteristics of granule neurons
and were detected in the olfactory bulb and dentate gyrus
(DG). Newer methods include the use of bromodeoxyuridine
(BrdU), which is incorporated along with 3H-thymidine into
cells during the S phase of the cell cycle to label prolifer-
ating cells and their progeny [15]. BrdU can be combined
with other immunohistochemical stains to identify specific
types of proliferating cells, such as neuronal nuclei,
neuron-specific enolase, and N-methyl-D-aspartate
receptor subunit NR1 [15].
Adult neurogenesis occurs in the subventricular zone
(SVZ) of the lateral ventricles and the subgranular zone
(SGZ) of the DG in the hippocampus (Fig. 2)[14]. The SVZ is
a paired brain structure that lies adjacent to the lateral
walls of the lateral ventricles [16]. Neural stem cells of the
SVZ migrate to the olfactory bulb via the rostral migratory
stream, where they differentiate into interneurons [13].
Because neurogenesis in the adult central nervous system
appears to be restricted to the DG and SVZ, studies have
focused on these two areas as targets for neurogenesis-
stimulating treatment [9,17].
The hippocampus, which plays a central role in learning
and memory, demonstrates a high degree of structural
plasticity [18,19]. Among the hippocampal formations, only
the DG continues to develop through adulthood. Progenitor
cells in the germinal zone of the DG continuously generate
granule cells, which integrate into the existing neuronal
circuits [15]. Thus, DG cell proliferation, differentiation,
and survival influence adult hippocampal neurogenesis [20].
Impaired hippocampal neuron replacement in adulthood
is associated with a number of neurologic conditions,
including epilepsy [21], stroke [22], Alzheimer’s disease
[23], Parkinson’s disease [24], and inflammation of the
brain [25]. The reduced proliferative activity of brain cells
associated with aging appears to be specific to granule cells
in the DG [26]. Neurogenesis increases in the hippocampus
and SVZ in the wake of epileptic seizures and ischemic
stroke, but it is not clear whether the new cells survive and
integrate to compensate for the brain injury [14]. Changes
in the local environment, such as a reduction in peptide
growth factors, may also play a role in age-related
impairments. Thus stimulating neurogenesis may be a key
factor in recovering from these conditions.
3. Acupuncture and Neurogenesis
Acupuncture stimulation has been used for more than 2000
years in East Asian countries as an integral part of the
medical armamentarium [27]. Traditional indications cover
a wide range of conditions, and a recent report from
a Consensus Panel on Acupuncture indicated that
acupuncture may be an effective adjunctive therapy for
addiction, stroke rehabilitation, headaches, menstrual
cramps, epicondylitis, fibromyalgia, lower back pain, carpal
tunnel syndrome, and asthma [28].
Regarding neurologic conditions, acupuncture has been
reported to be an effective therapy for brain disorders such
as sequelae of stroke [7], Parkinson’s disease [29], dementia
[30], and epilepsy [31]; however, its effectiveness for these
conditions remains controversial [32,33]. Studies conducted
Figure 1 Adult neural stem cells can self-renew and differ-
entiate into all major types of neural cells, including neurons,
astrocytes, and oligodendrocytes.
Figure 2 Adult neurogenesis occurs in two locations of the
brain: the subventricular zone of the lateral ventricles and the
subgranular zone of the dentate gyrus in the hippocampus.
Neural stem cells of the subventricular zone migrate to the
olfactory bulb via the rostral migratory stream, where they
differentiate into interneurons. Therefore, the dentate gyrus
and olfactory bulb are considered two neurogenic areas of the
adult central nervous system.
154 M.-H. Nam et al.
Author's personal copy
in Korea and China suggest that acupuncture may have the
potential to be developed as an adjunct for managing brain
disorders [34,35]. Acupuncture has been investigated using
functional magnetic resonance imaging of the brain [36,37],
electroencephalography [38], and physiological measure-
ments [39,40], but the precise mechanism underlying its
beneficial effects have not yet been elucidated.
Recent studies using rodent models have suggested that
acupuncture stimulates neurogenesis. In particular, stimu-
lating the following acupoints by acupuncture or electro-
acupuncture appears to induce neuronal proliferation: ST36
[41e43], GV20 [44], PC6 [45], HT7 [46], CV17, CV12, CV6,
SP10 [9], GV16, GV8 [47], LI11, SJ5, and GB30 [48]. Neuro-
genesis is regulated by a number of signaling pathways. In
rats, the cAMP response element-binding protein, a down-
stream target of cAMP signaling, is activated by electro-
acupuncture at ST36 and GV20. This transcription factor is
important in the proliferation,differentiation, and survival of
neuronal precursor cells, and directly regulates the expres-
sion of brain-derived neurotrophic factor, which supports the
growth, differentiation, and survival of neurons [49].
4. Neurogenesis effect of acupuncture
stimulation on ST36
ST36, an acupoint located on the anterior tibia muscle (Fig. 3),
is one of the most important acupoints in clinical acupuncture.
Simulation of ST36 is carried out for a wide range of conditions
affecting digestive system, cardiovascular system, and
immune system, and nervous system. Furthermore, ST36 is
one of the seven acupoints usedfor stroke treatment [50],and
has been widely used for brain disorders [30,51e53].
Recent studies have reported that acupuncture stimu-
lation may enhance adult neurogenesis at the SVZ and DG in
the brain (Table 1). In 2001, Kim et al provided the first
evidence for the increased generation of DG progenitor
cells after acupuncture treatment in ischemic gerbils (aged
11e13 weeks). Manual acupuncture at ST36 significantly
increased the number of BrdU-positive cells after ischemic
injury [42]. Subsequently, acupuncture stimulation at ST36
was reported to enhance cell proliferation in the DG a rat
model of diabetes [41]. In SAMP8 mice, which serve as
a model for Alzheimer’s disease, simulation of ST36, as well
as CV17, CV12, CV6, and SP10, induced cell proliferation in
different brain regions [9]. In healthy rats, acupuncture and
electroacupuncture stimulation at ST36 and GV20 signifi-
cantly increased cell proliferation in the SGZ of the DG [49],
and electroacupuncture stimulation at ST36, LI11, SJ5, and
GB30 produced a sustained effect on progenitor cell
proliferation and promoted cell differentiation in young
rats [48]. However, one study reported a beneficial effect
on neurogenesis with acupuncture stimulation at HT7, but
no effect at ST36 [46].
Several proteins found in the brain appear to be
increased by acupuncture therapy. Furthermore, stimula-
tion at ST36 upregulated the expression of neuropeptide Y,
which promotes the proliferation of neuronal precursor
cells [42,54]. In addition, modulation of brain-derived
neurotrophic factor expression appeared to mediate the
effects of electroacupuncture stimulation at ST36, which
attenuated the neuropathologic effects of stress in rats
[43]. Upregulation of brain-derived neurotrophic factor and
activation of the cAMP response element-binding protein in
the DG were also demonstrated in rats that exhibited
increased neuroblast plasticity after electroacupuncture at
ST36 and GV20 [49]. In this study, neurogenesis was
detected by immunostaining against Ki67, a marker of cell
proliferation, and doublecortin, which is specifically
expressed in neuronal precursors in the developing and
adult central nervous system [10,49].
5. Discussion: Neurogenesis Effect of ST36 and
the Primo Vascular System
Three reports have been published showing that acupunc-
ture stimulation at ST36 enhances cell proliferation in the
DG of the hippocampus [41e43]. Four additional studies
claimed that simultaneous stimulation at several acupoints
(including ST36) increased cell proliferation in the SGZ of
the DG [9,10,48,49]. Although one study [46] did not find
a beneficial effect with ST36, further investigation into the
mechanism behind the effects of acupuncture at ST36 on
adult neurogenesis is warranted.
An important first step in understanding the role of ST36
in neurogenesis is investigating the anatomy and physiology
of acupoints, in particular, identifying and characterizing
the anatomic structure connecting the acupoint ST36 and
the brain. Recently, the PVS was proposed as the anatomic
Figure 3 ST36, one of the most important and most
frequently stimulated acupoints, is located on the tibialis
anterior muscle. This figure originated from World Health
Organization Standard Acupuncture Point Locations.
Role of ST36 and the PVS in adult neurogenesis 155
Author's personal copy
Table 1 Summary of Papers on Adult Neurogenesis by Acupuncture at ST36
Study Year Animal model Acupoints Stimulation Results
Kim et al [42] 2001 Mongolian gerbils (11e13 weeks)
with transient global ischemia
ST36 Acupuncture; 20 min, 2 times/day for 9 days Acupuncture increased cell proliferation in
the dentate gyrus of ischemic gerbils.
Kim et al [41] 2002 Sprague Dawley rats (6 weeks) with
streptozotocin-induced diabetes
ST36 Acupuncture; 20 min, 2 times/day for 7 days Acupuncture at ST36 enhanced proliferation
of neuronal precursor cells in the dentate
gyrus.
Yun et al [43] 2002 Male Sprague Dawley rats (6 weeks) ST36 Electroacupuncture; 2 Hz, 1e2 mA, 0.3 ms
pulse width
Electroacupuncture restored brain-derived
neurotrophic factor expression attenuated
by immobilization stress.
Park et al [46] 2002 Sprague Dawley rats (14 days) ST36, HT7 Acupuncture; once per day for 1 week,
3emm
depth, both sides, twisting the needle
2 times/s
for 30 s, and removing immediately
Acupuncture at HT7 stimulated cell
proliferation in the dentate gyrus.
Acupuncture at ST36 did not produce
a significant effect.
*
Gao et al [48] 2011 Sprague Dawley rats (14 days) ST36, LI11, SJ5,
GB30
Electroacupuncture (2 Hz, 0.7 mV);
30 min,
once per day for 1 week
Electroacupuncture produced a sustained
effect on progenitor cell proliferation
and promoted differentiation into
neurons.
Hwang et al [10] 2010 Male Wistar rats (13 weeks) ST36, GV20 Acupuncture; 20 min, once per day
for 3 weeks at 5-mm depth
Electroacupuncture (dense-dispersed
waves of 5/20 Hz, 2e4 mA); 20 min, once
per day for 3 weeks at 5-mm depth
Both acupuncture and electroacupuncture
enhanced cell proliferation, but the effect
of electroacupuncture on neuroblast
differentiation in the dentate gyrus was
greater than that of acupuncture.
Hwang et al [49] 2010 Male Wistar rats (13 weeks) ST36, GV20 Electroacupuncture (dense-dispersed
waves of 5/20 Hz, 2e4 mA) 20 min, once
per day for 3 weeks at 5-mm depth
Electroacupuncture enhanced cell
proliferation and neuroblast
differentiation in the dentate gyrus.
Cheng et al [9] 2008 Male SAMP8 mice (4 months) ST36, CV17, CV12,
CV6, SP10
Acupuncture; once per day for 15 days
with a rest on day 8
Acupuncture treatment stimulated cell
proliferation in the dentate gyrus of
this autogenic senile strain.
* Maternal separation is known to increase the risk of emotional problems later in life; HT7 is used to treat neuropsychiatric disorders in
Oriental medicine.
156 M.-H. Nam et al.
Author's personal copy
structure of acupuncture meridians [55]. This idea was
originally put forth by Bong-Han Kim in the early 1960s [56],
but was ignored until recently because the Japanese
anatomist Fujiwara was the only researcher able to confirm
this discovery [57].
The PVS forms a network throughout the body in which
so-called primo fluid flows. This circulatory system has
several subsystems, one of which is the superficial PVS in
the skin, thought to correspond to acupuncture meridians
and acupoints [56]. The growth of the PVS around tumor
tissues has been characterized [58,59], as well as its
possible role as an additional pathway of cancer metastasis
[60]. The PVS has also been observed in the brain ventri-
cles, the central canal of the spinal cord [61], the
subarachnoid space of the brain [62], and along the
epineurium of the sciatic nerve [12]. These observations
are consistent with Bong-Han Kim’s claim that a primo
vessel from the primo node at ST36 has a course along the
sciatic nerve [56]. Primo vessels in the spinal nerves are
thought link the complex PVS network to the spinal cord
and brain, [63]. If ST36 is connected to the brain via the
PVS, the neurogenesis effect may be mediated by the
circulating fluid, which contains primo microcells [64,65]
that function like the very small embryonic-like stem cells
discovered by Ratajczak [66]. Bong-Han Kim claimed that
primo microcells may be involved in tissue regeneration,
similar to the role of pluripotent stem cells [63]. Thus,
appropriate stimulation at ST36 may promote adult neu-
rogenesis by improving the flow of primo microcells to the
brain. This hypothesis can be tested by investigating the
putative PVS path from the ST36 to the brain, followed by
characterizing the substances flowing along this path and
their therapeutic effects.
6. Conclusion
Adult neurogenesis, which may be a key process in recov-
ering from brain disorders, occurs in two distinct regions of
the brain: the SVZ of the lateral ventricles and the SGZ of
the DG. Numerous studies have reported that acupuncture
stimulation at ST36 appears to enhance adult neurogenesis.
Circulation through the PVS may be the underlying mech-
anism of this beneficial effect of acupuncture stimulation.
Acknowledgment
This work was supported by the Association of Korean
Oriental Medicine and Pilot Project 2011 of Advanced
Institute of Convergence Technology, Seoul National
University.
References
1. Stiles J, Jernigan TL. The basics of brain development. Neu-
ropsychol Rev. 2010;20:327e348.
2. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van
Praag H. When neurogenesis encounters aging and disease.
Trends Neurosci. 2010;33:569e579.
3. Altman J, Das GD. Autoradiographic and histological evidence
of postnatal hippocampal neurogenesis in rats. J Comp Neurol.
1965;124:319e335.
4. Landgren H, Curtis MA. Locating and labeling neural stem cells
in the brain. J Cell Physiol. 2011;226:1e7.
5. Hodge RD, Hevner RF. Expression and actions of transcription
factors in adult hippocampal neurogenesis. Dev Neurobiol.
2011;8:680e689.
6. Winner B, Kohl Z, Gage FH. Neurodegenerative disease and
adult neurogenesis. Eur J Neurosci. 2011;33:1139e1151.
7. Wu P, Mills E, Moher D, Seely D. Acupuncture in poststroke
rehabilitation: a systematic review and meta-analysis of
randomized trials. Stroke. 2010;41:e171ee179.
8. Lee MS, Shin BC, Ernst E. Acupuncture for Alzheimer’s disease:
a systematic review. Int J Clin Pract. 2009;63:874e879.
9. Cheng H, Yu J, Jiang Z, Zhang X, Liu C, Peng Y,et al. Acupuncture
improves cognitive deficits and regulates the brain cell prolif-
eration of SAMP8 mice. Neurosci Lett. 2008;432:111e116.
10. Hwang IK, Chung JY, Yoo DY, Yi SS, Youn HY, Seong JK, et al.
Comparing the effects of acupuncture and electroacupuncture
at Zusanli and Baihui on cell proliferation and neuroblast
differentiation in the rat hippocampus. J Vet Med Sci. 2010;72:
279e284.
11. Han TH, Lim CJ, Choi JH, Lee SY, Ryu PD. Viability assessment
of primo-node slices from organ surface primo-vascular tissues
in rats. J Acupunct Meridian Stud. 2010;3:241e248.
12. Jia ZF, Lee BC, Eom KH, Cha JM, Lee JK, Su ZD, et al. Fluores-
cent nanoparticles for observing primo vascular system along
sciatic nerve. J Acupunct Meridian Stud. 2010;3:150e155.
13. Taupin P, Gage FH. Adult neurogenesis and neural stem cells of
the central nervous system in mammals. J Neurosci Res. 2002;
69:745e749.
14. Zhao C, Deng W, Gage FH. Mechanisms and functional impli-
cations of adult neurogenesis. Cell. 2008;132:645e660.
15. Fuchs E, Gould E. Mini-review: in vivo neurogenesis in the adult
brain: regulation and functional implications. Eur J Neurosci.
2000;12:2211e2214.
16. Quinones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-
Perez O, Mirzadeh Z, Gil-Perotin S, et al. Cellular composition
and cytoarchitecture of the adult human subventricular zone:
a niche of neural stem cells. J Comp Neurol. 2006;494:
415e434.
17. Khaindrava V, Salin P, Melon C, Ugrumov M, Kerkerian-Le-
Goff L, Daszuta A. High frequency stimulation of the sub-
thalamic nucleus impacts adult neurogenesis in a rat model of
Parkinson’s disease. Neurobiol Dis. 2011;42:284e291.
18. Squire LR. The hippocampus and spatial memory. Trends
Neurosci. 1993;16:56e57.
19. Olson AK, Eadie BD, Ernst C, Christie BR. Environmental
enrichment and voluntary exercise massively increase neuro-
genesis in the adult hippocampus via dissociable pathways.
Hippocampus. 2006;16:250e260.
20. Kempermann G, Gage FH. Genetic determinants of adult
hippocampal neurogenesis correlate with acquisition, but not
probe trial performance, in the water maze task. Eur J Neu-
rosci. 2002;16:129e136.
21. Jessberger S, Zhao C, Toni N, Clemenson GD Jr, Li Y, Gage FH.
Seizure-associated, aberrant neurogenesis in adult rats char-
acterized with retrovirus-mediated cell labeling. J Neurosci.
2007;27:9400e9407.
22. Lindvall P, Kokaia Z. Neurogenesis following stroke affecting
the adult brain. In: Adult Neurogenesis (Cold Spring Harbor
Monograph Archive). New York: Cold Spring Harbor Laboratory
Press; 2008. p. 549e570.
23. Verret L, Jankowsky JL, Xu GM, Borchelt DR, Rampon C. Alz-
heimer’s-type amyloidosis in transgenic mice impairs survival
of newborn neurons derived from adult hippocampal neuro-
genesis. J Neurosci. 2007;27:6771e6780.
24. Winner B, Rockenstein E, Lie DC, Aigner R, Mante M, Bogdahn U,
et al. Mutant alpha-synuclein exacerbates age-related decrease
of neurogenesis. Neurobiol Aging. 2008;29:913e925.
Role of ST36 and the PVS in adult neurogenesis 157
Author's personal copy
25. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Inflam-
mation is detrimental for neurogenesis in adult brain. Proc Natl
Acad Sci U S A. 2003;100:13632e13637.
26. Kuhn HG, Dickinson Anson H, Gage FH. Neurogenesis in the
dentate gyrus of the adult rat: age-related decrease of neuronal
progenitor proliferation. J Neurosci. 1996;16:2027e2033.
27. Vanderploeg K, Yi X. Acupuncture in modern society. J Acu-
punct Meridian Stud. 2009;2:26e33.
28. National Institute of Health. National Institutes of Health
Consensus Development Conference Statement. Acupuncture.
1997.
29. Joh TH, Park HJ, Kim SN, Lee H. Recent development of
acupuncture on Parkinson’s disease. Neurol Res. 2010;32(Suppl
1):5e9.
30. Zhou Y, Jin J. Effect of acupuncture given at the HT 7, ST 36,
ST 40 and KI 3 acupoints on various parts of the brains of Alz-
heimer’s disease patients. Acupunct Electrother Res. 2008;33:
9e17.
31. Guo J, Liu J, Fu W, Ma W, Xu Z, Yuan M, et al. The effect of
electroacupuncture on spontaneous recurrent seizure and
expression of GAD (67) mRNA in dentate gyrus in a rat model of
epilepsy. Brain Res. 2008;1188:165e172.
32. Cheuk DK, Wong V. Acupuncture for epilepsy. Cochrane Data-
base Syst Rev. 2008:CD005062.
33. Zhang SH, Liu M, Asplund K, Li L. Acupuncture for acute stroke.
Cochrane Database Syst Rev. 2005:CD003317.
34. Han CH, Park SY, Ahn SY, Kwon OM, Ahn SW. A literature study
on the Korean acupuncture for the treatment of stroke. Kor J
Meridian Acupoint. 2009;26:145e163.
35.KimJS,LeeJD,ChoiDY,ParkYB,KohHK,AhnBC,etal.An
investigation into acupuncture treatment of verbal disturbance
after stroke. J Korean Acupunct Moxibustion Soc. 1998;15:
537e550.
36. Li G, Yang ES. An fMRI study of acupuncture-induced brain
activation of aphasia stroke patients. Complement Ther Med.
2011;19(Suppl 1):S49eS59.
37. Hui KK, Napadow V, Liu J, Li M, Marina O, Nixon EE, et al.
Monitoring acupuncture effects on human brain by fMRI. JVis
Exp. 2010;38.
38. Dhond RP, Kettner N, Napadow V. Neuroimaging acupuncture
effects in the human brain. J Altern Complement Med. 2007;
13:603e616.
39. Hsiu H, Huang SM, Chen CT, Hsu CL, Hsu WC. Acupuncture
stimulation causes bilaterally different microcirculatory
effects in stroke patients. Microvasc Res. 2011;81:289e294.
40. Pan S, Zhan X, Su X, Guo L, Lv L, Su B. Proteomic analysis of
serum proteins in acute ischemic stroke patients treated with
acupuncture. Exp Biol Med (Maywood). 2011;236:325e333.
41. Kim EH, Jang MH, Shin MC, Lim BV, Kim HB, Kim YJ, et al.
Acupuncture increases cell proliferation and neuropeptide Y
expression in dentate gyrus of streptozotocin-induced diabetic
rats. Neurosci Lett. 2002;327:33e36.
42. Kim EH, Kim YJ, Lee HJ, Huh Y, Chung JH, Seo JC, et al.
Acupuncture increases cell proliferation in dentate gyrus after
transient global ischemia in gerbils. Neurosci Lett. 2001;297:
21e24.
43. Yun SJ, Park HJ, Yeom MJ, Hahm DH, Lee HJ, Lee EH. Effect of
electroacupuncture on the stress-induced changes in brain-
derived neurotrophic factor expression in rat hippocampus.
Neurosci Lett. 2002;318:85e88.
44. Liu Q, Yu J, Mi WL, Mao-Ying QL, Yang R, Wang YQ, et al.
Electroacupuncture attenuates the decrease of hippocampal
progenitor cell proliferation in the adult rats exposed to
chronic unpredictable stress. Life Sci. 2007;81:1489e1495.
45. Lee B, Shim I, Lee HJ, Yang Y, Hahm DH. Effects of acupuncture
on chronic corticosterone-induced depression-like behavior
and expression of neuropeptide Y in the rats. Neurosci Lett.
2009;453:151e156.
46. Park HJ, Lim S, Lee HS, Lee HJ, Yoo YM, Kim SA, et al.
Acupuncture enhances cell proliferation in dentate gyrus of
maternally-separated rats. Neurosci Lett. 2002;319:153e156.
47. Yang ZJ, Shen DH, Guo X, Sun FY. Electroacupuncture enhances
striatal neurogenesis in adult rat brains after a transient
cerebral middle artery occlusion. Acupunct Electrother Res.
2005;30:185e199.
48. Gao J, Wang S, Wang X, Zhu C. Electroacupuncture enhances
cell proliferation and neuronal differentiation in young rat
brains. Neurol Sci. 2011;32:369e374.
49. Hwang IK, Chung JY, Yoo DY, Yi SS, Youn HY, Seong JK, et al.
Effects of electroacupuncture at Zusanli and Baihui on brain-
derived neurotrophic factor and cyclic AMP response
element-binding protein in the hippocampal dentate gyrus. J
Vet Med Sci. 2010;72:1431e1436.
50. Lee SH, Shin KH, Kim JU. Effect of Seven Points of CVA
Acupuncture on cerebral blood flow. J Korean Acupunct Mox-
ibustion Soc. 2004;21:83e98.
51. Kim ID, Oh HH, Song HC, Bom HS, Byun JY, Ahn SG. The nuclear
medical study on the effect of ST36 electroacupuncture on
cerebral blood flow. J Korean Acupunct Moxibustion Soc. 2001;
18:18e26.
52. Hsieh CL, Chang QY, Lin IH, Lin JG, Liu CH, Tang NY, et al. The
study of electroacupuncture on cerebral blood flow in rats with
and without cerebral ischemia. Am J Chin Med. 2006;34:
351e361.
53. Guo J, Liu J, Fu W, Ma W, Xu Z, Yuan M, et al. Effect of elec-
troacupuncture stimulation of hindlimb on seizure incidence
and supragranular mossy fiber sprouting in a rat model of
epilepsy. J Physiol Sci. 2008;58:309e315.
54. Hansel DE, Eipper BA, Ronnett GV. Neuropeptide Y functions as
a neuroproliferative factor. Nature. 2001;410:940e944.
55. Soh KS. Bonghan circulatory system as an extension of acupunc-
ture meridians. J Acupunct Meridian Stud. 2009;2:93e106.
56. Kim BH. On the Kyungrak system. J Acad Med Sci. 1963;10:
1e41.
57. Fujiwara S, Yu SB. ‘Bonghan theory’ morphological studies.
Igaku no Ayumi. 1967;60:567e577.
58. Yoo JS, Kim HB, Ogay V, Lee BC, Ahn SY, Soh KS. Bonghan Ducts
as possible pathways for cancer metastasis. J Acupunct
Meridian Stud. 2009;2:118e123.
59. Yoo JS, Ayati MH, Kim HB, Zhang WB, Soh KS. Characterization
of the primo-vascular system in the abdominal cavity of lung
cancer mouse model and its differences from the lymphatic
system. PLoS ONE. 2010;5:e9940.
60. Yoo JS, Kim HB, Won N, Bang J, Kim S, Ahn S, et al. Evidence for
an additional metastatic route: in vivo imaging of cancer cells
in the primo-vascular system around tumors and organs. Mol
Imaging Biol. 2010;13:471e480.
61. Lee BC, Kim S, Soh KS. Novel anatomic structures in the brain
and spinal cord of rabbit that may belong to the Bonghan
system of potential acupuncture meridians. J Acupunct
Meridian Stud. 2008;1:29e35.
62. Lee BC, Eom KH, Soh KS. Primo-vessels and primo-nodes in rat
brain, spine and sciatic nerve. J Acupunct Meridian Stud. 2010;
3:111e115.
63. Kim BH. The Kyungrak system. J Jo Sun Med. 1965;108:1e38.
64. Baik KY, Ogay V, Jeoung SC, Soh KS. Visualization of Bonghan
microcells by electron and atomic force microscopy. J Acu-
punct Meridian Stud. 2009;2:124e129.
65. Johng HM, Yoo JS, Yoon TJ, Shin HS, Lee BC, Lee C, et al. Use of
magnetic nanoparticles to visualize threadlike structures
inside lymphatic vessels of rats. Evid Based Complement
Alternat Med. 2007;4:77e82.
66. Ratajczak MZ, Zuba-Surma EK, Shin DM, Ratajczak J, Kucia M.
Very small embryonic-like (VSEL) stem cells in adult organs and
their potential role in rejuvenation of tissues and longevity.
Exp Gerontol. 2008;43:1009e1017.
158 M.-H. Nam et al.
