Introduction
Post-stroke depression (PSD) is considered to be the
most common and severe mental illness after stroke. Approximately
one-third of stroke survivors suffer from severe depression, which
can adversely affect a patient's cognitive function, functional
recovery, and survival. It is generally believed that the damaged
neural circuits of emotion regulation caused by stroke are the main
cause of PSD. Gastrodin is one of the major active extracts of the
root of Gastrodia elata Bl (1). Gastrodin is often used for
anti-convulsions, analgesia, sedation, and is also used in the
treatment of vertigo, paralysis and other diseases. In addition,
studies have shown that gastrodin can promote learning and memory
abilities (2). Gastrodin has also
been proven to be able to protect cortical neurons and astrocytes
from injury and reduce ischemic-induced neuronal damage (3,4).
However, the clinical effects of gastrodin on PSD have not been
well studied.
As a neurotransmitter, 5-HT is involved in the
regulation of pain, sleep and body temperature and other
physiological functions. The abnormal content and function of 5-HT
in the central nervous system may be associated with mental
illness, migraine and other diseases (5). The neurotrophic factor (BDNF) is a
brain-derived protein that plays an important role in the survival,
differentiation, growth and development of neurons during the
development of the central nervous system. Studies have shown that
BDNF deficiency can lead to post-traumatic stress disorder, which
is commonly known as phobia (6). The
aim of this study was to investigate the effects of gastrodin on
levels of 5-HT and BDNF in PSD patients and to assess the efficacy
of gastrodin in the treatment of PSD.
Patients and methods
Clinical data
A total of 78 patients with PSD were selected from
September 2013 to December 2016 in Binzhou City Center Hospital
(Binzhou, China). The patients included 40 males and 38 females,
and the age ranged from 48 to 76 years with an average age of
62.7±6.45 years. This study was approved by the Ethics Committee of
Binzhou City Center Hospital. All the patients signed an informed
consent.
Diagnostic criteria for stroke
Stroke was diagnosed according to the 2014 edition
of ‘Guide to the diagnosis and treatment of acute cerebral ischemic
stroke in China’ (7): i) acute
onset; ii) combined with systemic or focal neurological deficits;
iii) neurological deficit signs and symptoms last longer than
hours; iv) transcranial CT and magnetic resonance imaging (MRI) of
ischemic lesions are consistent with clinical signs; and v)
exclusion of non-vascular cerebral hemorrhage and brain lesions by
brain CT and MRI.
Diagnostic criteria for anxiety and
depression
Anxiety and depression were diagnosed according to
the diagnostic criteria described in the ‘Chinese Mental Disorder
Classification and Diagnosis Standards 3rd Edition’ proposed by the
Chinese Medical Association Psychiatric Branch (8): i) loss of pleasure and interest; ii)
fatigue and limited energy; iii) long-term low self-evaluation; iv)
reduced self-thinking ability, manifested as mental retardation or
excitement; v) sleep disorder; vi) self-injury and motivation; and
vii) libido, appetite, and body weight different from what they
used to be prior to PSD.
Inclusion criteria
i) All patients included in this study were
clinically diagnosed with stroke diagnosis; ii) patients without
drug allergies; iii) patients who had no anxiety and depression
before stroke; and iv) patients who had clear consciousness and
certain communication skills.
Exclusion criteria
i) patients with anxiety and depressive symptoms;
ii) patients with suicidal tendencies; iii) patients with nervous
system dysfunction and past severe heart, liver, and kidney
dysfunction; iv) patients with history of drug allergies; v)
patients who were treated within 7 days before admission; and vi)
patients unable to complete treatment.
Treatment
The 78 patients were randomly divided into the
control group (21 were males and 18 were females) and experimental
group (18 were males and 21 were females), 39 cases in each group.
Patients in the control group were treated with conventional drug
fluoxetine hydrochloride capsules (Lilly Suzhou Pharmaceutical
Group Co., Ltd., Suzhou, China; SFDA approval no. J20130010) with a
dose of 12.5 mg each time and 3 times per day. Patients in the
control group were treated with gastrodin capsules (KPC
Pharmaceuticals Inc., Kunming, China; SFDA approval no. H20013043)
with a dose of 25 mg each time and 3 times per day. All patients
were treated for 2 months.
Measurement of indicators
Hamilton Depression (HAMD) scale, Activities of
Daily Living (ADL) scale, NIH Stroke Scale/Score (NIHSS) and Stroke
Impact Scale (SIS) scoring were performed by the same physician
before, and at 1 and 2 months after treatment. Blood samples were
collected from each patient before and at 1 and 2 months after
treatment. The levels of neurotrophic factor (BDNF) and
5-hydroxytryptamine (5-HT) were measured using the BDNF ELISA kit
(cat. no. 3765; R&D Systems, Inc., Minneapolis, MN, USA) and
5-HT ELISA kit (cat. no. 4493; R&D Systems, Inc.). Side effects
mainly include systemic or local allergies, gastrointestinal
disorders (such as nausea, vomiting, dyspepsia, diarrhea and
dysphagia), anorexia, dizziness, headache, abnormal sleep, fatigue,
mental state abnormalities, visual abnormalities, xeromycteria,
dizziness and stomach upset. Adverse effects were recorded. Total
effective rate (%) = (number of cured patients + number of patients
showed partial improvement)/total number of patients.
Statistical analysis
Data were analyzed by GraphPad Prism software
(version 5.01). Measurement data were expressed as mean ± SD. ANOVA
was used for comparison between multiple groups and the post hoc
test was Dunnett's test. Percentage (%) was used to express the
enumeration data and Chi-square test was used for data analysis.
P<0.05 was conside-red to indicate a statistically significant
difference.
Results
Comparison of the general information
between the two groups of patients
As shown in Table I,
no significant differences in age, sex, types of stroke and course
of PSD were found between the two groups (P>0.05).
 | Table I.Comparison of the general information
between two groups. |
Table I.
Comparison of the general information
between two groups.
| Items | Control group
(n=39) | Experimental group
(n=39) | χ2
value | P-value |
|---|
| Age (years) | 65.10±9.5 | 66.72±7.9 | 1.45 | 0.934 |
| Sex (male) n (%) | 21 (53.85%) | 19 (48.72%) | 1.43 | 0.981 |
| Stroke type n
(%) |
|
| 3.87 | 0.726 |
|
Atherosclerosis | 14 (35.90%) | 13 (33.33%) |
|
|
| Cardiac
embolism | 11 (28.21%) | 12 (30.77%) |
|
|
| Lacunar
infarction | 13 (33.33%) | 10 (25.64%) |
|
|
|
Other | 1 (2.56%) | 4
(10.26%) |
|
|
| Course of PSD
(days) | 22.51±3.73 | 24.67±2.87 | 4.75 | 0.254 |
Comparison of 5-HT levels between the
two groups before and after treatment
Before treatment, no significant differences in the
levels of 5-HT were found between the two groups (P>0.05).
Compared with the preoperative levels, the 5-HT levels were
significantly increased in the two groups of patients at 1 and 2
months after treatment (P<0.05). In addition, the 5-HT levels
were significantly higher in the experimental group than those in
the control group at 1 and 2 months after treatment (P<0.05;
Table II).
| Table II.Comparison of 5-HT levels between the
two groups before and after treatment (mean ± SD, ng/ml). |
Table II.
Comparison of 5-HT levels between the
two groups before and after treatment (mean ± SD, ng/ml).
| Groups | n | Before treatment | 1 month after
treatment | 2 months after
treatment |
|---|
| Control group | 39 | 65.34±8.45 |
92.57±10.58a |
124.64±14.05b |
| Experimental
group | 39 | 67.51±7.02 |
107.82±10.23b,d |
148.51±12.83c,d |
| t value |
| 0.552 | 1.232 | 1.784 |
| P-value |
| 0.683 | 0.0371 | 0.0107 |
Comparison of BDNF levels between the
two groups before and after treatment
No significant differences in the levels of BDNF
were found between the two groups before treatment (P>0.05).
Compared with the preoperative levels, the BDNF levels were
significantly increased in the two groups of patients at 1 and 2
months after treatment (P<0.05). In addition, the levels of BDNF
were significantly higher in the experimental group than those in
the control group at 1 and 2 months after treatment
(P<0.05)(Table III).
| Table III.Comparison of BDNF levels between the
two groups before and after treatment (mean ± SD, ng/ml). |
Table III.
Comparison of BDNF levels between the
two groups before and after treatment (mean ± SD, ng/ml).
| Groups | n | Before treatment | 1 month after
treatment | 2 months after
treatment |
|---|
| Control group | 39 | 8.03±1.72 |
14.09±2.16a |
19.29±3.62b |
| Experimental
group | 39 | 7.67±1.53 |
18.38±2.07a,c |
25.78±4.41b,c |
| t value |
| 0.348 | 0.984 | 1.127 |
| P-value |
| 0.829 | 0.0403 | 0.0336 |
Comparison of HAMD scores between the
two groups of patients before and after treatment
There were no significant differences in HAMD scores
between the two groups before treatment (P>0.05). Compared with
the preoperative levels, HAMD scores were significantly decreased
in the two groups of patients at 1 and 2 months after treatment
(P<0.05). Compared with the control group, HAMD scores were
significantly reduced in the experimental group (P<0.05)
(Table IV).
| Table IV.Comparison of HAMD scores between the
two groups of patients before and after treatment (mean ± SD). |
Table IV.
Comparison of HAMD scores between the
two groups of patients before and after treatment (mean ± SD).
| Groups | n | Before treatment | 1 month after
treatment | 2 months after
treatment |
|---|
| Control group | 39 | 27.37±1.65 |
17.58±1.43a |
12.96±0.79b |
| Experimental
group | 39 | 26.83±1.84 |
12.26±1.51a,c |
7.92±0.98b,c |
| t value |
| 0.380 | 0.946 | 1.165 |
| P-value |
| 0.675 | 0.0366 | 0.0341 |
Comparison of ADL and NIHSS scores
between the two groups before and after treatment
As shown in Table V,
compared with the preoperative levels, ADL scores were
significantly increased and NIHSS scores were significantly
decreased in both groups at 1 and 2 months after treatment
(P<0.05). Compared with the control group, significantly higher
ADL scores and lower NIHSS scores were found in the experimental
group at 1 and 2 months after treatment (P<0.05).
| Table V.Comparison of ADL and NIHSS scores
between the two groups before and after treatment (mean ± SD). |
Table V.
Comparison of ADL and NIHSS scores
between the two groups before and after treatment (mean ± SD).
| Items | Groups | n | Before
treatment | 1 month after
treatment | 2 months after
treatment |
|---|
| ALD | Control group | 39 | 54.57±6.87 |
67.19±7.30a |
74.14±8.22b |
|
| Experimental
group | 39 | 55.79±7.82 |
72.04±8.93a,c |
91.36±9.69b,c |
|
| t value |
| 0.576 | 1.664 | 2.486 |
|
| P-value |
| 0.728 | 0.0207 | 0.00839 |
| NIHSS | Control group | 39 | 20.45±1.88 |
16.76±1.74a |
12.73±1.96a |
|
| Experimental
group | 39 | 21.31±2.04 |
13.06±1.78a,c |
7.78±1.53b,c |
|
| t value |
| 0.453 | 1.352 | 1.743 |
|
| P-value |
| 0.816 |
0.0458 | 0.0397 |
Comparison of SIS scores between the
two groups before and after treatment
This study evaluated 6 items including strength,
hand function, mood, communication, activity and action. As shown
in Table VI, no significant
differences in SIS scores were found between the two groups before
treatment. SIS scores were significantly increased in both groups
at 1 month and 2 months after treatment (P<0.05). In addition,
SIS scores were higher in the experimental group than those in the
control group (P<0.05).
| Table VI.Comparison of SIS scores between the
two groups before and after treatment (mean ± SD). |
Table VI.
Comparison of SIS scores between the
two groups before and after treatment (mean ± SD).
| Items | Groups | n | Before
treatment | 1 month after
treatment | 2 months after
treatment |
|---|
| Strength | Control group | 39 | 65.45±5.23 |
70.56±6.44a |
76.31±7.72a |
|
| Experimental
group | 39 | 64.50±5.85 |
75.33±7.72a,c |
82.76±9.82b,c |
|
| t value |
| 0.434 | 0.893 | 0.932 |
|
| P-value |
| 0.681 | 0.0403 | 0.0394 |
| Hand function | Control group | 39 | 48.08±4.76 |
52.61±5.73a |
58.42±6.31a |
|
| Experimental
group | 39 | 48.53±4.37 |
55.17±6.34a,c |
61.94±4.66b,c |
|
| t value |
| 0.595 | 0.752 | 1.135 |
|
| P-value |
| 0.890 | 0.0417 | 0.0381 |
| Mood | Control group | 39 | 60.74±3.24 |
63.45±3.86a |
67.27±4.15a |
|
| Experimental
group | 39 | 59.37±3.38 |
66.83±4.29a,c |
73.74±4.86b,c |
|
| t value |
| 0.674 | 0.914 | 1.382 |
|
| P-value |
| 0.715 | 0.0487 | 0.0176 |
| Communication | Control group | 39 | 78.22±7.84 |
81.36±8.36a |
85.58±9.57a |
|
| Experimental
group | 39 | 77.39±7.30 |
84.66±8.59a,c |
92.68±10.06b,c |
|
| t value |
| 0.526 | 0.876 | 1.226 |
| Activity | P-value |
| 0.662 | 0.0429 | 0.0203 |
|
| Control group | 39 | 65.92±10.66 |
68.94±10.37a |
71.64±11.09a |
|
| Experimental
group | 39 | 66.53±9.84 |
71.44±11.27a,c |
76.63±11.85a,c |
|
| t value |
| 0.487 | 0.994 | 0.987 |
| Action | P-value |
| 0.770 | 0.0311 | 0.0462 |
|
| Control group | 39 | 72.25±11.67 |
75.88±11.24a |
79.15±11.08a |
|
| Experimental
group | 39 | 72.94±11.40 |
77.98±10.45a,c |
83.56±12.36a,c |
|
| t value |
| 0.502 | 1.153 | 1.432 |
|
| P-value |
| 0.693 | 0.0265 | 0.0201 |
Comparison of treatment efficacy
between the two groups
Two months after treatment, 11 patients in the
control group showed side effects, 14 cases were cured, 12 cases
were effective, and 13 cases were invalid, and the total effective
rate was 66.67% (26/39). While, only 7 cases in the experimental
group showed side effects, 19 cases were cured, 15 cases were
effective, and 5 cases were invalid, and the total effective rate
was 87.18% (34/39). Therefore, treatment efficacy was significantly
higher in the experimental group than that in the control group
(P<0.05) (Table VII).
| Table VII.Comparison of treatment efficacy
between the two groups. |
Table VII.
Comparison of treatment efficacy
between the two groups.
| Groups | n | Side effects | Percentage | Cure | Effective | Ineffective | Total effective
rate |
|---|
| Control group | 39 | 11 | 28.21% | 14 | 12 | 13 | 66.67% |
| Experimental
group | 39 | 7 | 17.95%a | 19 | 15 | 5 | 87.18%a |
| χ2
value |
|
| 1.65 |
|
|
| 1.79 |
| P-value |
|
| 0.0285 |
|
|
| 0.0327 |
Discussion
With an aging population that continues to grow, the
incidence of hypertension, diabetes, hyperlipidemia and other
stroke related diseases are increasing, which in turn leads to the
increased incidence of stroke (8,9). PSD is
the most common complication of stroke. The incidence of PSD in
China is estimated to be approximately 30–35%, and many patients
develop depression several hours to several days after stroke
(10). There are two opposing views
on the mechanism for the occurrence of PSD. It is believed that the
damaged neural circuits of emotion regulation and central nervous
system induced by ischemic injury after stroke are the main cause
of PSD (11,12). While other studies have shown that
stroke-related social and psychological stress is the main cause of
PSD (13,14).
Conventional treatment of PSD includes controlling
hypertension, reducing high cholesterol, prohibiting smoking,
blocking excitatory neurotransmitters, preventing cerebral
ischemia, or scavenging free radicals (15,16), but
those treatments usually fail to provide satisfactory treatment
outcomes. As an adjunctive therapy, Chinese medicine becomes more
and more important in the treatment of PSD. For example,
Hypericumperfortum extracts have been proven to be effective in the
treatment of depression (17). In
this study, gastrodin was used to treat PSD and showed excellent
clinical therapeutic effects. Studies have shown that gastrodin is
an important component extracted from traditional Chinese medicine
gastrodia, which is a commonly used drug for clinical treatment.
Gastrodin can remove free radicals in the body, delay the process
of apoptosis, protect cell membranes, and simultaneously expand
blood vessels and regulate blood viscosity and compliance. In
addition, gastrodin can inhibit the production of monoamine
oxidase, increase brain dopamine and 5-HT contents, thereby
exerting anxiolytic and depressive effects (18,19).
This study selected gastrodin as a research object for the
treatment of PSD and excellent clinical effects were observed.
BDNF and 5-HT play pivotal roles in the regulation
of synaptic plasticity in adult (20). As a member of the family of
neurotrophic factors, BDNF plays a pivotal role in brain
development and plasticity by promoting nerve regeneration,
synaptic plasticity and cell survival (21,18).
5-HT is produced by neurons located in the brain stem, and it can
also promote the survival of neurons in the adult brain (19). The axons that produce 5-HT neurons
dominate normative behavior in multiple cerebral cortical and
subcortical regions including cognition and mood (22,23).
Disrupted 5-HT and BDNF signaling pathways are the main causes of
depression, and studying the levels of 5-HT and BDNF in PSD
patients is an important way to expose the molecular mechanism.
In this study, we found that gastrodin could
significantly increase the levels of 5-HT and BDNF in patients with
PSD. In addition, HAMD and NIHSS scores were significantly
decreased and ADL and SIS scores were significantly increased at 1
and 2 months after treatment with gastrodin. Compared with
fluoxetine hydrochloride, gastrodin has less side effects and good
efficiency. Gastrodin can effectively alleviate depression and
improve the quality of life of patients. In conclusion, gastrodin
can be used to effectively treat PSD and should be popularized in
clinical practices.
Acknowledgements
Not applicable.
Funding
No funding was received.
Availability of data and materials
The datasets used and/or analyzed during the present
study are available from the corresponding author on reasonable
request.
Authors' contributions
GL drafted the manuscript. GL and YM were mainly
devoted to collecting and interpreting the data. JJ and XS revised
it critically for important intellectual content and were also
involved in the conception and design of the study. QF was
responsible for the conception and design of the study. All authors
have read and approved the final manuscript.
Ethics approval and consent to
participate
The study was approved by the Ethics Committee of
Binzhou City Center Hospital (Binzhou, China). Signed informed
consents were obtained from the patients.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing
interests.
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