Adult Neurogenesis and Neurological Disorders Special Section

Study on Effects and Mechanism of Lead and High-Fat Diet on Cognitive Function and
Central Nervous System in Mice
Yiwei Huang1 and Keming Yun2

- OBJECTIVE: We sought to investigate the effects and triglyceride, low-density lipoprotein, IL-6, IL-17, interferon
mechanism of lead and a high-fat diet on cognitive function g, and AGEs of the remaining 3 groups increased signifi-
and the central nervous system in mice. cantly, but the recognition index, passing platform times,
high-density lipoprotein, and GSH-ST significantly
- METHODS: Eighty-four healthy male mice were
decreased (P < 0.05); the second and third escape latent
randomly divided into a control group (n [ 21) (fed with
periods, IL-6, IL-17, and AGEs of lead D high-fat group,
common diet and free drinking), a lead exposure group
were obviously higher than the remaining 3 groups, but the
(n [ 21) (fed with common diet and 300 mg/L lead acetate
passing platform times were obviously lower than the
solution), a high-fat group (n [ 21) (fed with high-fat diet
remaining 3 groups, of which the difference was statisti-
and free drinking), and a lead D high-fat group (n [ 21)
cally significant. The content of hydrogen peroxide in brain
(fed with high-fat diet and 300 mg/L lead acetate solution).
tissues had no difference among groups (P > 0.05).
In 10 weeks after lead exposure, the mice of all groups
were tested for the cognition, learning and memory abili- - CONCLUSIONS: The lead and high-fat diet resulted in
ties, body weight, serum triglyceride (TG), low-density li- lipid metabolism disorders and impaired the cognitive
poprotein, and high-density lipoprotein, as well as for the function and central nervous system by promoting the
contents of lead, interleukin 6 (IL-6), interleukin 17 (IL-17), secretion of inflammatory factors in glial cells, inducing
interferon g, advanced glycation end products (AGEs), the inflammatory reaction of brain tissue, inhibiting GSH-
glutathione S-transferase (GSH-ST), and hydrogen peroxide ST expression, and increasing AGEs content.
in the brain tissues.
- RESULTS: Compared with the control group and the
lead-exposed group, the body weights of mice in the high-
fat group and the lead D high-fat group increased signif-
INTRODUCTION
icantly from the sixth week of the experiment, of which the
difference was statistically significant (P < 0.05). Compared
with the control group and the high-fat group, the lead
content in brain tissue of the lead exposure group and the
lead D high-fat group increased significantly, of which the
L ead is a kind of neurotoxic heavy metal. It has been found
in studies that lead in the environment can be stored in the
central nervous system (CNS) and cause cognitive function
defects and other damage.1 Because lead is widely used in
production and life, lead exposure has become an increasingly
difference was statistically significant (P < 0.05). Compared serious environmental and medical problem.2 The CNS is the
with the control group, the escape latent period, main target organ of lead injury. Lead exposure can affect the

Key words TG: Triglyceride

- Central nervous system
- Cognitive function From the 1Department of Neurology, Zhuji Affiliated Hospital of Shaoxing University, Zhuji,
- High-fat diet Zhejiang; and 2College of Forensic Medicine, Shanxi Medical University, Taiyuan City, Shanxi
- Lead exposure Province, China
- Mechanism
To whom correspondence should be addressed: Keming Yun, Ph.D.
[E-mail: sxmukeming@126.com]
Abbreviations and Acronyms
Citation: World Neurosurg. (2020) 138:758-763.
AGE: Advanced glycation end product
https://doi.org/10.1016/j.wneu.2020.01.165
GSH-ST: Glutathione S-transferase
HDL: High-density lipoprotein Journal homepage: www.journals.elsevier.com/world-neurosurgery
IFN-g: Interferon g Available online: www.sciencedirect.com
IL-17: Interleukin 17 1878-8750/$ - see front matter ª 2020 Elsevier Inc. All rights reserved.
IL-6: Interleukin 6
LDL: Low-density lipoprotein

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YIWEI HUANG AND KEMING YUN
ability of learning and memory and damage the sensory organs
and their innervation. At present, there is much research on the
mechanism of lead nerve injury. For instance, lead can induce
oxidative stress, leading to cell injury, apoptosis, and excitatory
toxicity. In addition, a high-fat diet can result in a significant
decrease in the expression level of the hippocampus-related
functional proteins and damage hippocampal neurons, thereby
affecting the function of the nervous system and causing inat-
tention, decline of learning ability, cognitive function disorder,
and other symptoms.3,4
At present, it is still unclear what the mechanism of the com-
bined effect of lead and high-fat diet on the function of the CNS is.
There are many studies on the damage of a lead and high-fat diet
to the cerebral cortex, hippocampus, neurons, and CNS disorders,
but there are few studies on the causes. In this study, the mouse
models of lead and high-fat diet exposure were established to
investigate the changes and mechanisms of cognitive function and
CNS function after the effect of the lead and high-fat diet.
Furthermore, it provides a new basis and target for the prevention
of neural injury in the lead-exposed occupational population,
especially in the obese population. The innovation of this paper is
to take obese people as the main research object, which has
obvious pertinence.
MATERIALS AND METHODS
Animals
Eighty-four healthy adult male mice of Grade SPF were selected
from Beijing Vital River Laboratory Animal Technology Co., Ltd.
(SCXK[Jing] 2009-0004). The weight of each mouse was 12
17 g.
All mice were fed in the independent ventilated animal feeding
cage of the laboratory. During the experiment, the temperature of
the laboratory was maintained at (23  2) C, the humidity at (55 
5)% and the light time for 12 hours. All mice were fed with the
same common feed and drinking water for 1 week and then
averagely divided into 4 groups by the method of random number
table, namely control group, lead exposure group, high-fat group,
and lead þ high-fat group. Each group had 21 mice. There was no
significant difference in general data (body weight and monthly
age) of the mice in each group. The animal experiments and an-
imal treatment processes involved in this study meet the re-
quirements of animal experiment standardization, and the
protocol was approved by the ethics committee of our hospital.
Grouping and Treatment
The control group was fed with ordinary feed and normal drinking
water; the lead exposure group with ordinary feed and lead acetate
solution (300 mg/L); the high-fat group with high-fat feed and
normal drinking water; and the lead þ high-fat group with high-
fat feed and lead acetate solution (300 mg/L). For all mice, the diet
was not restricted but supplemented in time. The general condi-
tion of the mice was observed every day. Their diets were recorded
respectively, and all mice were weighed every 2 weeks. After
continuous exposure for 10 weeks, neurologic function tests were
carried out in each group of mice to test their cognitive, learning,
and memory abilities.
WORLD NEUROSURGERY 138: 758-763, JUNE 2020
ADULT NEUROGENESIS AND NEUROLOGICAL DISORDERS SPECIAL SECTION
LEAD/HIGH-FAT DIET EFFECTS ON MOUSE CNS
Enzyme-Linked Immunosorbent Assay
The mice were then sacrificed to take the serum and brain tissue
samples. The contents of serum lipometabolic product and in-
flammatory factor in the brain tissue were tested by the enzyme-
linked immunosorbent assay; the corresponding kit was selected
to determine the contents of advanced glycation end products
(AGEs), glutathione S-transferase (GSH-ST), and hydrogen
peroxide in the brain tissue in strict accordance with the in-
structions, and the content of lead in brain tissue was tested by
inductively coupled plasma mass spectrometry.
Testing for Cognitive Ability
Twenty-four hours before training, we put the mice in a special
experimental device to let them freely adapt to the environment.
Next, we placed two objects of the same shape, size, and color at
the left and right ends on a side of the box; put the mice into the
box with their backs against the objects; and recorded the
cognitive time that the mice respectively smelled, watched, and
touched the 2 objects in 3 minutes. The test was carried out 24
hours after the training. We replaced 1 object in the box with a
new object of different shape and size. We kept other methods
similar to the training period and recorded the cognitive time of
the mice for 2 new and old objects. During the whole experiment,
it was necessary to keep quiet indoors. After each experiment, we
washed the device thoroughly with 75% alcohol for fear that odor
might affect the test results of the mice. Cognitive index (%) ¼
cognitive time of new object/(cognitive time of new
object þcognitive time of old object)  100%.
Morris Water Maze
The mice were tested by a Morris water maze for learning and
memory ability. Before the beginning of the formal experiment,
the adaptive training was carried out for the mice for 1 day and the
mice were put into the water maze at the 4-quadrant starting point
with their faces toward the pool wall. Then, they could freely find
the underwater platform and the activity track in 2 minutes was
recorded. The formal experiment lasted for 4 days. In the first 3
days, the fixed navigation experiment was carried out to measure
learning ability. The methods were the same as those of the
training period. The time of finding the platform was recorded,
namely escape latent period. If the mice did not find the platform
in 2 minutes, they were guided to the platform to stay 5 seconds
and the escape latent period was recorded as 120 seconds. On the
final day, the space exploration experiment was carried out to
measure the spatial memory ability of mice. The underwater
platform was removed, and the experimental mice were put in
from the opposite quadrant of the platform with their faces toward
the pool wall. The number of times that the mice passed through
the platform in 1 minute were observed and recorded.
Observation Indices
We included general conditions and body weights; lead content in
brain tissue; serum lipid metabolism index including triglyceride
(TG), low-density lipoprotein (LDL), and high-density lipoprotein
(HDL); neural function including cognitive ability and learning/
memory ability; content of inflammatory factor in brain tissue
including interleukin 6 (IL-6), interleukin 17 (IL-17), and interferon
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 ADULT NEUROGENESIS AND NEUROLOGICAL DISORDERS SPECIAL SECTION
YIWEI HUANG AND KEMING YUN LEAD/HIGH-FAT DIET EFFECTS ON MOUSE CNS

g (IFN-g) in brain tissue; and the AGEs, GSH-ST, and hydrogen

peroxide contents in the brain tissue of mice.
400
The content of lead in the blood of mice was detected by
inductively coupled plasma-mass spectrometry. The mice were 350
anesthetized with isoflurane, and 200
500 uL blood were taken
300

Lead content (pg/g)

from the eyeballs and put into a 1.5-mL EP tube containing 20 uL
heparin sodium, which was stored at
4 C. We took 200 uL 250
anticoagulant blood and put it into a Teflon digestive tube, added
200
2 mL concentrated nitric acid, and digested it with microwave
digestion instrument. After complete digestion, we transferred the 150
liquid into a 10-mL EP tube and diluted it to 5 mL with 1% nitric
100
acid for use.
The TG content in the serum of mice was detected by Kit. The 50
color of quinones produced by the GPO-PAP method was directly
0
proportional to the content of triglycerides, the OD value was Control Lead exposure High-fat Lead + high-fat
determined by enzyme scale instrument, and the TG content in 照 暴露
group 高脂
group +高脂
group group
samples was calculated.
Figure 2. Comparison of lead content in brain tissue.

Statistical Treatment
All data were analyzed by SPSS22.0 data analysis software. The
SNK test was used to compare the groups with homogeneity of
group and the lead þ high-fat group were significantly higher than
variance, while the Games-Howell test was adopted to compare
those of the control group and lead exposure group, of which the
the groups with irregular variances. When P < 0.05, it was
difference was statistically significant (P < 0.05).
considered that the difference was statistically significant.

RESULTS Lead Contents in Brain Tissue of All Groups

Changes of General Conditions and Body Weights of Rice
The weight changes of the 4 groups of mice during the experiment
are shown in Figure 1. No poisoning or death occurred in all
groups during the whole experiment period. There was no
significant difference in food intake and drinking water volume.
The mice acted normally with smooth hair. The mass of the
mice in each group presented an upward trend during the
experiment. There was no significant difference for body
weights between the control group and the lead exposure group
and between the high-fat group and lead þ high-fat group
(P > 0.05); from the sixth week, the body weights of the high-fat
50
The comparison results of lead content in brain tissue of 4 groups
of mice are shown in Figure 2. There was no significant difference
in lead content in the brain tissue between the control group and
the high-fat group (P > 0.05), and the lead contents in the brain
tissues of the 2 groups were significantly lower than those of the
lead exposure group and the lead þ high-fat group, of which the
difference was statistically significant (P < 0.05).
Lipometabolic Product Content in Serum
Table 1 shows the content comparison of serum lipid metabolites
of the 4 groups of mice. The contents of serum TG, HDL, and LDL
of the high-fat group and the lead þ high-fat group were signif-
icantly higher than those of the control group and the lead
exposure group, of which there was significant difference

40 Table 1. Comparison of Lipometabolic Product Content in

Serum (mmol/L)
Lead mass (g)

30 Group TG HDL LDL

20 Control group (n ¼ 21) 0.50  0.13 0.71  0.13 0.49  0.15

Lead exposure group 0.62  0.21 0.63  0.15 0.58  0.12
10 (n ¼ 21)
High-fat group (n ¼ 21) 0.91  0.16① 0.43  0.07① 1.02  0.18①
0 Lead þ high-fat group 0.98  0.25①② 0.37  0.08①② 1.07  0.20①②
Before test 第2周
Week 2 Week
第4周4 Week 6
第6周 Week 8 Week
第8周 第10周 10 (n ¼ 21)
Control
照 Lead
暴露 exposure High-fat
高脂 Lead
+高脂+ high-fat
group group group group Compared with the control group, ① P < 0.05; compared with the lead exposure group,
② P < 0.05.
Figure 1. Comparison of body weights during experiment. TG, triglyceride; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

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 ADULT NEUROGENESIS AND NEUROLOGICAL DISORDERS SPECIAL SECTION
YIWEI HUANG AND KEMING YUN LEAD/HIGH-FAT DIET EFFECTS ON MOUSE CNS

IL-6, IL-17, and IFN-g in the brain tissues of the lead exposure
group, high-fat group, and lead þ high-fat group were signifi-
0.8
cantly higher than that of the control group, of which the differ-
ences were statistically significant (P < 0.05). In addition, the
0.6 contents of serum IL-6 and IL-17 in the lead þ high-fat group were
Cognitive index (%)

significantly higher than those of the lead exposure group and the
high-fat group, of which the differences were statistically signifi-
0.4 cant (P < 0.05).

AGEs, GSH-ST, and Hydrogen Peroxide Contents in Brain Tissue

0.2
0
Control Lead exposure High-fat
照 暴露 高脂
group group group
Figure 3. Comparison of cognitive index.
(P < 0.05). Compared with the control group, the contents of
serum TG, HDL, and LDL of lead exposure group did not change
significantly, of which the difference was not statistically signifi-
cant (P > 0.05).
Nerve Functions of All Groups
Figure 3 and Table 2 show the comparison of cognitive indexes
and learning and memory abilities of the 4 groups of mice. The
cognitive indices of the lead exposure group, the high-fat group,
and the lead þ high-fat group were significantly lower than those
of the control group, but the day 3 escape latent period was
significantly longer than the control group and the passing plat-
form times significantly decreased, of which the differences were
statistically significant (P < 0.05); in addition, the day 2 and day 3
escape latent periods of the lead þ high-fat group were signifi-
cantly longer than those of the lead exposure group and the high-
fat group, but the passing platform times decreased significantly,
of which the differences were statistically significant (P < 0.05).
Inflammatory Factor Content in Brain Tissue
Table 3 and Figure 4 show the comparison results of inflammatory
factor content in brain tissue of 4 groups of mice. The contents of
Table 4 shows the comparison results of AGE, GSH-ST, and
hydrogen peroxide contents in brain tissues of 4 groups of mice.
The contents of AGEs in the brain tissues of the lead exposure
Lead + high-fat
group, the high-fat group, and the lead þ high-fat group were
+高脂 significantly higher than that of the control group, but the GSH-ST
group
content decreased, of which the differences were statistically sig-
nificant (P < 0.05). In addition, the contents of AGEs in the lead þ
high-fat group were significantly higher than those of the lead
exposure group and the high-fat group, of which the differences
were statistically significant (P < 0.05). There was no significant
difference (P > 0.05) for hydrogen peroxide contents in the brain
tissues of all groups.
DISCUSSION
By comparing the lead exposure and high-fat diet mice models,
this study has found that the lead content in the brain tissues of
the lead exposure group and the lead þ high-fat group increased
significantly and the body weights of the high-fat group and the
lead þ high-fat group increased as well. In addition, compared
with the control group, the escape latent periods were obviously
prolonged and the passing platform times decreased obviously in
the other 3 groups, of which the change was the most significant
in the lead þ high-fat group. It indicated that a lead and high-fat
diet might lead to decrease of the cognitive ability and learning/
memory ability of the mice and obvious damage to the function of
the nervous system.
Body weight is always adopted to reflect the health condition of
laboratory animals during the animal experiment.5 As 1 of the fat
ingredients, TG mainly comes from decomposition of the fat in
the in-taken food. TG can be widely accumulated in blood ves-
sels, subcutaneous tissues, and visceral organs. Appropriate TG
has the effects of keeping body temperature and buffering the

Table 2. Comparison of Learning and Memory Abilities

Escape Latent Period (seconds)

Group Day 1 Day 2 Day 3 Passing Platform Times (Times)

Control group (n ¼ 21) 65.97  11.24 53.68  11.95 33.01  7.88 4.52  1.37
① ① ①
Lead exposure group (n ¼ 21) 100.13  8.92 83.33  17.41 70.14  12.96 2.63  0.76①
① ① ①
High-fat group (n ¼ 21) 104.51  14.03 86.73  20.89 69.18  11.21 2.25  0.77①
Lead þ high-fat group (n ¼ 21) 105.26  19.58① 103.06  22.79①②③ 91.49  15.84①②③ 1.21  0.63①②③

Note: Compared with the control group, ① P < 0.05; compared with the lead exposure group, ② P < 0.05; compared with the high-fat group, ③ P < 0.05.

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 ADULT NEUROGENESIS AND NEUROLOGICAL DISORDERS SPECIAL SECTION
YIWEI HUANG AND KEMING YUN LEAD/HIGH-FAT DIET EFFECTS ON MOUSE CNS

Table 3. Comparison of Inflammatory Factor Contents in Brain Table 4. Comparison of AGEs, GSH-ST, and Hydrogen Peroxide
Tissue Contents in Brain Tissue
Group IL-6 IL-17 IFN-g Hydrogen
Peroxide
Control group 0.35  0.05 0.27  0.03 0.06  0.01 Group AGEs (ng/mg) GSH-ST (U/mg) (mmol/g)
(n ¼ 21)
Control group (n ¼ 21) 10.17  1.12 41.03  7.01 3.09  0.23
Lead exposure group 0.40  0.07① 0.31  0.04① 0.08  0.01①
(n ¼ 21) Lead exposure group 11.97  1.20① 26.81  6.73① 3.21  0.26
(n ¼ 21)
High-fat group 0.39  0.05① 0.30  0.05① 0.08  0.02①
(n ¼ 21) High-fat group (n ¼ 21) 14.68  1.37① 25.96  8.07① 3.10  0.31
①②③ ①②③ ① ①②③
Lead þ high-fat group 0.45  0.08 0.35  0.05 0.09  0.02 Lead þ high-fat group 17.01  1.31 25.99  5.49① 3.12  0.27
(n ¼ 21) (n ¼ 21)

Note: Compared with the control group, ① P < 0.05; compared with the lead exposure
group, ② P < 0.05; compared with the high-fat group, ③ P < 0.05.
pressure, but too much TG in the serum may result in dyslipi-
demia and atherosclerosis.6,7 The main physiologic function of
HDL is to transport the lipoprotein molecules in the blood to
cells of all body tissues, effectively remove the cholesterol in the
blood vessels, and prevent arteriosclerosis.8 LDL is a lipoprotein
responsible for transporting fatty acid molecules in the blood,
and its cholesterol level is positively correlated with the
incidence of various cardiovascular diseases.9 The results of this
study showed that the body weights of the mice fed with a
high-fat diet increased significantly from the sixth week of the
experiment. The contents of serum TG and LDL increased
significantly, but the content of HDL decreased significantly.
Compared with the high-fat group, the above changes were more
obvious in the lead þ high-fat group, which means that lead and
high-fat diet exposure could aggravate the disorder of lipid
metabolism in mice.
Many studies have shown that a lead and high-fat diet mainly
endangers the cortex and hippocampus areas in brain tissue,
damages neurons, and causes disorder of the central nervous
IL-6
IL-17
IFN-y
0.4
0.3
Content
Note: Compared with the control group, ① P < 0.05; compared with the lead exposure
group, ② P < 0.05; compared with the high-fat group, ③ P < 0.05.
AGE, advanced glycation end product; GSH-ST, Glutathione S-transferase.
system.10,11 Glial cells in the CNS can secrete inflammatory
factors, such as IL-6, IL-17, and IFN-g.12,13 AGEs can damage
normal physiologic structure of the protein and destroy protein
performance by cross-linking with protein. Meanwhile, AGEs
can specifically combine with receptors on the cell surface,
changing physiologic function of cells.14 GSH-ST can catalyze the
binding of glutathione with intermediate products transformed by
exogenous chemical poisons in living bodies and thus play a role
in detoxification and protecting DNA from being damaged.15 This
study has found that, compared with the control group, the IL-6,
IL-17, and IFN-g contents in the serum of the other 3 groups
increased significantly, and the lead þ high-fat group was the
most obvious. In addition, compared with the control group, the
content of AGEs in the other 3 groups increased significantly, but
GSH-ST content decreased obviously, of which the high-fat group
showed the most obvious change, suggesting that a lead and high-
fat diet would aggravate oxidative stress and inflammatory reac-
tion and damage the CNS in mice. The results of this study are
basically consistent with those of Guillemot-Legris et al.3 The
ability of autonomous inquiry of obese mice was decreased, and
the retention time of lead exposure obese mice in the central
area was more obvious than that of alone obese and lead
exposure mice.
In conclusion, the combined exposure of a lead and high-fat
diet can cause lipid metabolism disorder and obvious damage to
cognitive ability and the CNS. The mechanism is that a lead and

high-fat diet promotes glial cells to secrete inflammatory factors

and induce inflammatory reaction in brain tissue to cause the
0.2
damage, inhibit GSH-ST expression, and increase AGEs, which
further aggravates the injury of brain tissue. This study provides a
0.1 basis for the prevention of neurologic damage in a lead-exposed
population. In addition, this study is aimed at obese people,
which has a strong pertinence, and can provide suggestions for
0.0
the daily life habits of obese people. However, the related
group ad exposure igh-fat group d + high-fat
Control Le H Lea signaling pathways of Th17, Treg, and other inflammatory cells
involved in the occurrence and development of neurodegenerative
Figure 4. Comparison of IL-6, IL-17, and IFN-g contents in brain tissues of
4 groups of mice.
diseases need to be further explored, which will be the specific
direction of follow-up studies.

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YIWEI HUANG AND KEMING YUN
REFERENCES
1. Xing LI, Ning LI, Sun HL, et al. Maternal lead
exposure induces down-regulation of hippocam-
pal insulin-degrading enzyme and nerve growth
factor expression in mouse pups. Biomed Environ
Sci. 2017;30:215-219.
2. Weifeng M, Dajin Y, Haixia S, et al. Assessment of
lead exposure risk in diets of Chinese adult resi-
dents. Chin J Food Hyg. 2016;28:107-110.
3. Guillemot-Legris O, Masquelier J, Everard A, et al.
High-fat diet feeding differentially affects the
development of inflammation in the central ner-
vous system. J Neuroinflammation. 2016;13:206.
4. Raider K, Ma D, Harris JL, et al. A high fat
diet alters metabolic and bioenergetic function in
the brain: a magnetic resonance spectroscopy
study. Neurochem Int. 2016;97:172.
5. Xiang W, Yaohua H, Hongyu X, et al. Effect of
resveratrol on expression of inflammatory factors
related to pulmonary hypertension of experi-
mental rabbits. China J Mod Med. 2016;26:10-15.
6. Khetarpal SA, Rader DJ. Triglyceride-rich lipo-
proteins and coronary artery disease risk. Arte-
rioscler Thromb Vasc Biol. 2015;35:3-9.
7. Nordestgaard BG. Triglyceride-rich lipoproteins
and atherosclerotic cardiovascular disease: new
WORLD NEUROSURGERY 138: 758-763, JUNE 2020
ADULT NEUROGENESIS
LEAD/HIGH-FAT DIET EFFECTS ON MOUSE CNS
insights from epidemiology, genetics, and
biology. Circ Res. 2016;118:547-563.
8. Quispe R, Martin SS, Jones SR. Triglycerides to
high-density lipoprotein-cholesterol ratio, glyce-
mic control and cardiovascular risk in obese pa-
tients with type 2 diabetes. Curr Opin Endocrinol
Diabetes Obes. 2016;23:1.
9. Leibowitz M, Karpati T, Cohenstavi CJ, et al. As-
sociation between achieved low-density lipopro-
tein levels and major adverse cardiac events in
patients with stable ischemic heart disease taking
statin treatment. JAMA Intern Med. 2016;176:
1105-1113.
10. Kang Beipei, Zhao Fang, Su Peng, et al. Role of
XIAP expression change in lead-induced mouse
hippocampal neuron cell injury. Pract Prevent Med.
2015;22:513-516.
11. Petrov D, Pedrós I, Artiach G, et al. High-fat diet-
induced deregulation of hippocampal insulin
signaling and mitochondrial homeostasis de-
ficiencies contribute to Alzheimer disease pathol-
ogy in rodents. Biochim Biophys Acta. 2015;1852:
1687-1699.
12. Tingting T, Wenfeng Y, Zhizhong G. Enhanced
expression of inflammatory cytokines and nuclear
factor-kb in microglia by overdose fluoride. Chin J
Endemiol. 2015;34:785-789.
www.journals.elsevier.com/world-neurosurgery
AND NEUROLOGICAL DISORDERS SPECIAL SECTION
13. Wang JB, Li H, Wang LL, et al. Role of IL-1b, IL-6,
IL-8 and IFN-g in pathogenesis of central nervous
system neuropsychiatric systemic lupus erythem-
atous. Int J Clin Exp Med. 2015;8:16658.
14. Song J, Lee WT, Park KA, et al. Receptor for
advanced glycation end products (RAGE) and its
ligands: focus on spinal cord injury. Int J Mol Sci.
2014;15:13172.
15. Roncalli V, Cieslak MC, Passamaneck Y, et al.
Glutathione s-transferase (GST) gene diversity in
the crustacean Calanus finmarchicus—contributors to
cellular detoxification. PLos One. 2015;10:e0123322.
Conflict of interest statement: The authors declare that the
article content was composed in the absence of any
commercial or financial relationships that could be construed
as a potential conflict of interest.
Received 26 December 2019; accepted 20 January 2020
Citation: World Neurosurg. (2020) 138:758-763.
https://doi.org/10.1016/j.wneu.2020.01.165
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2020 Elsevier Inc. All
rights reserved.
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