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dOI 10.11603/IJMMR.2413-6077.2019.2.10459

SOME METABOLIC pROCESSES IN THE pATIENTS WITH LONG-TERM 
CONSEQUENCES OF MILD TRAUMATIC BRAIN INJURY 

Ye. Lekomtseva
INSTITUTE OF NEUROLOGY, PSYCHIATRY AND NARCOLOGY OF THE NATIONAL ACADEMY  

OF MEDICAL SCIENCES OF UKRAINE, KHARKIV, UKRAINE

Background. Mild traumatic brain injury (mTBI) leads to disturbance of various metabolic processes 
significant in pathogenesis of the maintaining of long-term consequences after it. 

The objective of the research was to analyse changes in the activity of some membrane-associated enzyme 
markers, which are involved in different redox reactions, reflecting main metabolic processes.

Methods. Forty-seven patients with long-term consequences of mTBI, thirty controls were enrolled. The levels 
of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase (LDH), 
gamma-glutamyl transpeptidase were evaluated in sera by gas-liquid chromatograph and calorimetric methods.

Results. The study revealed significant changes in metabolic processes observed for alkaline phosphatase 
and LDH, which were the indicators of membrane and redox processes disturbances, acidosis severity and impaired 
energy cell metabolism. The averages of LDH level was 662.7 versus 381.9 U/L, in the controls. The disease 
progression was followed by directly proportional LDH increase reaching very high values in the patients with 
disease duration more than 15 years (mean ±SD 144.6±16.3 versus 82.6±8.4 U/L, controls p<0.05). The long-term 
consequences of mTBI were characterized by statistically significant decrease of alkaline phosphatase and positive 
dependence (p<0.05) of it (r=+0.48) on the disease duration with the averages of alkaline phosphatase level of 
152.5±11.21 versus 212.6±9.63 U/L, controls (p<0.01). The significance of changes in membrane-associated 
enzymes serum levels correlated with development of oxidative stress and metabolic processes dysfunction.

Conclusion. In the patients with long-term consequences of mTBI, dysregulation of enzymes activity was 
detected that might be a marker of nervous system energy impairment and membranes destruction.

KEY WORDS: long-term consequences of mTBI; membrane-associated enzymes; metabolic 
processes.

Corresponding author: Yevgeniya Lekomtseva, MD, Ph.D., State 
Institute of Neurology, Psychiatry and Narcology of the Na-
tional Academy of Medical Sciences of Ukraine, Department of 
Neurology, Department of Functional Neurosurgery and 
Paroxysmal States, 46 Academic Pavlov Str, Kharkiv, 61068, 
Ukraine.
E-mail: yevgeniyalekomtseva@gmail.com

Introduction
Mild traumatic brain injury is a leading 

cause of disability in young people [2, 21]. 
Neurotrauma leads to disturbance of various 
types of metabolic processes that are significant 
in the pathogenesis of maintaining of long-term 
consequences after it [9, 12, 15]. It is established 
that metabolic disturbances are based on 
biochemical reactions proceeding with parti-
cipation of enzymes located in various parts of 
the cell [3, 7, 22]. Most of these enzymes are 
inside the cell or mitochondria and appear in 
blood or cerebral spinal fluid only when cells 
are damaged, and this is of great diagnostic 
and prognostic importance. Thus, the changes 
in any parameters of membrane-associated 

enzymes evidence for disturbances of metabolic 
processes of biochemical redox reactions, cell 
or mitochondria destruction or development 
of membrane pathology [1, 4, 18, 20].

Enzymes are proteins, each type has a 
unique function facilitating catalyzation of 
routine and vital chemical reactions in the 
organisms [5, 17, 19]. Among the most sensitive 
and widely used membrane-associated enzy-
mes are aspartate aminotransferase (AST) and 
alanine aminotransferase (ALT); in addition to 
them, alkaline phosphatase and lactate de-
hydrogenase (LDH) are the other interesting 
enzymes. LDH is not specific to the liver and can 
be elevated in many other diseases related to 
inflammation in tissues [16, 18]. Human studies 
have shown that serum levels of autoantibodies 
(anti-nuclear antibody, anti-smooth muscle 
antibody, and anti-liver and kidney microsomal 
antibody) are elevated in patients with auto-
immune hepatitis and some rare muscle neuro-
degenerative disorders [6, 8, 10]. Symptoms of 

International Journal of Medicine and Medical Research 
2019, Volume 5, Issue 2, p. 25-31
copyright © 2019, TNMU, All Rights Reserved

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long-term consequences after mild traumatic 
brain injury can or cannot be present in the 
patients with mild increase of metabolic enzy-
mes [4, 13, 21] and symptoms of posttraumatic 
period are not specific, thus the membrane­
associated enzyme abnormalities can some-
times provide us with the useful clarification of 
a cause of the condition.

According to these issues, the objective of 
research was to analyze the dynamics of 
changes in the activity of some indicators of 
membrane-associated enzymes, which are 
involved into certain redox reactions, reflecting 
the main metabolic processes in the patients 
with long-term consequences of mild traumatic 
brain injury.

Methods
Forty-seven patients with long-term conse-

quences of mild traumatic brain injury (mTBI) 
of the average age of 47.41±9.37 years old (16 
women, 34.05% and 31 men, 65.95%) and the 
average disease duration (mean±SD, 12.67±8.92 
years old) were enrolled into the study. The 
definition of mTBI was consistent with the 
World Health Organization’s International Sta-
tistical Classification of Diseases and Related 
Health Problems (ICD­10; 1992) [2]. Thirty healthy 
volunteers (Control; mean±SD, 35.6±9.21 years) 
without neurological and psychiatry diseases 
were involved as well.

In the anamnesis, the investigated patients 
suffered from concussion (n=18; 38.29% among 
them there were eleven women, 61.11% and 
twenty men, 38.9%) and mild brain contusion 
(n=29; 61.71%, 17.24% women and 82.76% men). 
The patients were treated with symptomatic 
therapy. Inclusion criteria involved the patients 
of above 18 years of age with nonpenetrating 
head injury and initial Glasgow coma scale 
score more than 7 (mean±SD, 10.37±2.14). 
Exclusion criteria were craniectomy and sepsis 
in the anamnesis, pregnancy, preexisting 
neurologic diseases, acute cardiovascular di-
seases, respiratory failure, any acute or chronic 
liver diseases.

Clinical data of each case were retrieved 
from the patients’ history. Physical and neuro-
logical examinations were performed for all 
patients, CT and/or MRI, EEG recording were 
retrieved as well. Neurological examination 
revealed focal neurological signs, indicating 
mesencephalic and brainstem structures le-
sions; the most frequent were tendon reflexes 
increase in 23 patients (41.07 %), coordination 
disturbances – 21 patients (37.5 %), ataxia – 

15 patients (26.78 %), horizontal nystagmus – 
11 patients (19.64 %), pathological foot reflexes – 
8 patients (14.28 %) and rotator nystagmus – 
5 patients (8.93 %).

Aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), alkaline phosphatase, 
lactate dehydrogenase (LDH), creatine kinase 
and gamma-glutamyl transpeptidase (GGT) 
were detected in sera by the gas-liquid chro-
matography and the calorimetric methods 
according to the standard protocols provided 
by the manufacture using commercially 
available human ELISA kits (Clinical Biochemistry 
Department, Kharkiv National Medical Uni-
versity). Controls and individual sampling were 
performed in duplicate manner with a coefficient 
of variation of <10 % (P values ≤0.05); all pro­
tocols were approved by the local Ethics 
Committee; written informed consents were 
obtained from all patients.

Age and disease duration were compared 
between the groups by the χ2 test; parametric 
tests were used for normally distributed data; 
nonparametric tests were used for abnormal 
distributed data; Kruskal­Wallis and Mann­
Whitney U tests were applied in Prism regarding 
the differences between groups, the multivariate 
analysis considering covariates was performed.

Results
The results of all patients examinations 

have revealed the significant changes in mem­
brane-associated enzymes serum levels mani-
fested as the increase of creatine kinase (CK) 
serum levels by 41.4%, LDH by 73.5% and 
decrease of alkaline phosphatase serum levels 
to 28.3% and a tendency of GGT serum level 
decrease to 18.7% in the general clinical group 
(Table 1). 

Analysis of the dynamics of the membrane-
associated enzymes markers in the patients 
with long-term consequences of mTBI proved 
that the most severe and statistically significant 
changes were observed for two enzymes: 
alkaline phosphatase and LDH, which are the 
indicators of cell or mitochondria membrane 
damage, acidosis severity, isolation of redox 
processes and phosphorylation, impaired 
energy metabolism in cells.

Metabolic changes in the examined patients 
evidenced that the content of serum LDH, a key 
glycolysis enzyme, was increased in almost all 
patients, and this increase was in a direct 
proportion with the disease progression or 
longer posttraumatic period (p<0.05; r=+0.36). 
We found the elevated LDH level in serum 

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samples of the investigated patients compare 
to HC (p=0.01, t=5.08); in the general patient 
group the medians of total LDH level was 
662.7 U/L and 381.9 U/L, in controls, respectively.

To evaluate the clinical prognostic value of 
LDH changes we further segregated among the 
different disease duration groups. When com-
paring the LDH serum level in the patients with 
different duration of the post-traumatic period 
after mTBI, it was proved that the patients with 
the disease duration no longer than 5 years 
(n=14; 29.78%) were characterized by increase 
of LDH serum levels by 27.8% (p>0.05). In the 
patient group with the disease duration from 
5 to 15 years (n=11; 23.4%), the LDH was 
increased to 78.6% (p=0.05) with average level 
of 682.4±24.8 U/L, and in the patients with the 
disease duration more than 15 years (n=22; 
46.8%), the LDH was increased to 105.2% 
(p=0.01) with average level of 783.6±31.4 U/L. 

The revealed increase of LDH serum level, in 
our opinion, was a marker of increased memb-
rane destruction as a result of metabolic dis-
turbances. It should be noted that in the patients 
with long-term consequences for more than 15 
years, LDH serum level was higher compare to 
HC and average group indicators, which, in our 
opinion, was a poor prognostic sign.

When comparing the alkaline phosphatase 
serum level in the patients with different dura-

tion of post-traumatic period after mTBI, it was 
found that the patients with the disease dura-
tion no longer than 5 years was characterized 
by 8.5% decreasing (p>0.05) of alkaline phos-
phatase serum level. In the patients with the 
disease duration between 5 and 15 years, the 
mean serum level of alkaline phosphatase was 
decreased by 24.1% (p>0.05); in the patients 
with the disease duration more than 15 years, 
alkaline phosphatase level was decreased by 
27.6% (p<0.01) in sera.

At the same time, further disease progress 
or longer posttraumatic period was accom-
panied by directly proportional increase of CK 
serum levels: the values remained higher than 
the controls with an average of (mean ±SD) 
116.8±19.4 U/L (p<0.05) in the general group 
and reached statistically significant values in 
the patients with the disease duration more 
than 15 years (mean ±SD 144.6±16.3 U/L versus 
82.6±8.4 U/L controls; p<0.05). However, long­
term consequences of mTBI revealed quite 
significant increase in CK level by 50.3% com­
pare to the patients of the subgroup with the 
duration of the posttraumatic period less than 
5 years. This correlated positively with a higher 
frequency of various neurological syndromes 
(p<0.05; r= +0.63) for long­term consequences 
of mTBI and might be a biochemical marker of 
the latter neurological deficit.

Table 1. The dynamics of the markers of membrane-associated enzymes serum levels in the 
patients with long-term consequences after mild traumatic brain injury

Data All patients(general group)

Dependence from the post-traumatic period duration
up to 5 years

(stage 1)
from 5 to15 years 

(stage 2)
more than 15 years

(stage 3)
AST, (U/L) 29.6±3.3

p>0.05
26.6±2.9
p>0.05 

27.3±4.8
p>0.05

30.3±7.1
p>0.05

Controls 25,2±1,9
ALT, (U/L) 22.8±3.9

p>0.05
21.8±4.2
p>0.05

21.4±2.1
p>0.05

23.5±3.7
p>0.05

Controls 20,5±1,4
Alkaline phospha-
tase, (U/L)

152.5±11.21
p<0.01

194.6±6.7
p>0.05

161.3±15.3
p>0.05

153.9±9.8
p<0.01

Controls 212,6±9,63
LDH, (U/L) 662.7±21.9

p=0.01
488.3±36.3

p>0.05
682.4±23.1

p=0.05
783.6±18.4

p=0.01
Controls 381.9 ±28,1 
CK, (U/L) 116.8±19.4

p<0.05 
109.5±27.1

p>0.05 
126.4±22.6

p>0.05 
144.6±16.3

p<0.05 
Controls 82,6±8,4
GGT, (U/L) 14.8±6.2

p>0.05
19.6±3.5
p>0.05

15.9±9.3
p>0.05

14.1±4.2
p>0.05

Controls 18,2±1,4

Note. p – significance compared to the control group.

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The same dynamics was evidenced with the 
respect to GGT serum level but without sta-
tistically significant changes: the GGT serum 
level at stage 1 and stage 2 practically did not 
differ from the control. In the remaining group 
of the patients, there was a decrease of GGT 
serum levels compare to HC (mean ±SD 
14.1±4.2 versus 18.2±1.4 U/L) but also without 
any statistically significant changes (p>0.05).

Discussion
The attained data complied with the lite-

rature, in our opinion reflecting the effect of the 
increasing deficiency of oxidative reactions in 
the body on aminoacid metabolism in this 
category of patients [11, 12, 14]. The decrease in 
some markers of membrane-associate enzymes 
activity could be a marker of impaired metabolic 
processes following long-term con sequences 
after mTBI. The revealed increase of membrane-
associate markers enzymes in the patients with 
long-term consequences after mTBI was directly 
proportional to the severity of neurological 
deficit (p<0.05; r= +0.63) as a result of the de­
velop ment of membrane cell or mitochondrial 
membrane pathology and that might be a mar-
ker of the degree of nervous system damage. In 
turn, the destruction of cell membranes was 
pathoge netically associated with the develop-
ment of oxidative stress [6, 15, 16, 18].

The long-term consequences after mTBI 
was characterized by the statistically significant 
decrease of alkaline phosphatase serum level 
and positive dependence of alkaline phos-
phatase (p<0.05; r=+0.48) on the disease dura­
tion reflecting the specificity of the revealed 

changes in its activity in cases of cell energy 
deficiency in this category of the patients, which 
was an important diagnostic criterion. The 
decrease in alkaline phosphatase activity accor-
ding to the previous literature [7, 10] might be 
a marker of impaired intracellular metabolism 
in long-term consequences of mTBI.

In the general patient group, there was a 
significant increase in CK serum level compare 
to controls with the maximal biochemical values 
in the third clinical group with long-term 
consequences of mTBI more than 15 years and 
combined in 18.2% of the patients (n=4) with 
partial epileptic seizures. In our opinion, the 
direct proportional increase in CK activity with 
the progression and increase of posttraumatic 
period was associated (p<0.05; r= +0.63) with 
development of destructive processes in cells 
as a result of oxidative stress and disturbance 
of intracellular bioenergetic processes. It was 
noteworthy that the CK increase in cases of 
posttraumatic encephalopathy in the patients 
with long-term consequences more than 15 
years did not reach the same value (according 
to the literature) as in hereditary neuromuscular 
diseases and this might be a differential diag-
nostic criterion for posttraumatic ence pha-
lopathy. Slightly different dynamic was observed 
analysing the information about another 
enzyme involved into exchange of amino acids 
and peptides – GGT. At the first and second 
stages, a tendency of GGT serum level decrease 
was evidenced, which could not be significant 
in the patients with disease duration more than 
15 years compare to the control. This data 
complied with the literature on GGT serum level 

Figure 1. Analysis of the dynamics of lactate dehydrogenase and creatine kinase levels in the patients after 
traumatic brain injury with different duration of posttraumatic period.

Note. p – significance compared to the control group. 

When comparing the alkaline phosphatase serum level in the patients with different
duration of post-traumatic period after mTBI, it was found that the patients with the disease 
duration no longer than 5 years was characterized by 8.5% decreasing (p>0.05) of alkaline 
phosphatase serum level. In the patients with the disease duration between 5 and 15 years, the 
mean serum level of alkaline phosphatase was decreased by 24.1% (p>0.05); in the patients with 
the disease duration more than 15 years, alkaline phosphatase level was decreased by 27.6% 
(p<0.01) in sera. 

At the same time, further disease progress or longer posttraumatic period was 
accompanied by directly proportional increase of CK serum levels: the values remained higher than 
the controls with an average of (mean ±SD) 116.8±19.4 U/L (p<0.05) in the general group and 
reached statistically significant values in the patients with the disease duration more than 15 years 
(mean ±SD 144.6±16.3 U/L versus 82.6±8.4 U/L controls; p<0.05). However, long-term consequences 
of mTBI revealed quite significant increase in CK level by 50.3% compare to the patients of the 
subgroup with the duration of the posttraumatic period less than 5 years. This correlated positively 
with a higher frequency of various neurological syndromes (p<0.05; 
r= +0.63) for long-term consequences of mTBI and might be a biochemical marker of the latter 
neurological deficit. 

488,3

682,4
783,6

381,9

109,5 126,4
144,6

82,6

0

100

200

300

400

500

600

700

800

900

posttraumatic period 
<5 years

posttraumatic period 
5-15 years

posttraumatic period 
>15 years

control

U
/L

lactate dehydrogenase creatine kinase

Figure 1. Analysis of the dynamics of lactate dehydrogenase and creatine kinase levels in the 
patients after traumatic brain injury with different duration of posttraumatic period.

The same dynamics was evidenced with the respect to GGT serum level but without 
statistically significant changes: the GGT serum level at stage 1 and stage 2 practically did not differ 
from the control. In the remaining group of the patients, there was a decrease of GGT serum levels 
compare to HC (mean ±SD 14.1±4.2 versus 18.2±1.4 U/L) but also without any statistically significant 
changes (p>0.05). 

Discussion

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decrease in the patients, who suffered from 
severe TBI [2, 19] reflecting, in our opinion, the 
developing deficiency of oxidative reactions on 
amino acid metabolism in these patient groups 
and/or associated with long treatment with 
different painkillers and/or antiepileptic drugs.

At present, there is still no effective 
pharmacological treatment that stops the 
progression of secondary brain injury; the 
pathogenetic mechanisms of secondary 
traumatic brain injuries development are still 
unclear and urgent. Thereby, the further 
research on any other related markers and 
membrane-associated enzymes involved in 
internal redox reactions in the patients with 
long-term consequences of traumatic brain 
injury is topical.

Conclusion
Thus, in the patients with long-term 

consequences of mTBI, dysregulation of 

enzymes activity was detected that might be a 
marker of nervous system energy processes 
impairment and membranes destruction. The 
severity of the changes in the serum levels of 
membrane-associated enzymes markers 
correlated with the development of oxidative 
stress and metabolic processes dysfunction. 
The revealed dysregulation of enzymes activity 
might be caused by dystrophic cell changes, 
their disfunction and metabolic changes 
reflecting the severity of neurological symptoms.

Acknowledgement
Author would like to thank enormously 

Gorbach T.V., Ph.D. (Kharkiv National Medical 
University, Clinical Biochemistry Department) 
for support in this research.

Funding
This research received no external funding.
Conflict of Interests
The author declares no conflict of interest.

стан метаБолічних процесіВ у хВорих з Віддаленими наслідками 
легкоЇ закритоЇ черепно-мозкоВоЇ траВми

Є.В. Лекомцева 
ДУ "ІНСТИТУТ НЕВРОЛОГІЇ, ПСИХІАТРІЇ ТА НАРКОЛОГІЇ

 НАЦІОНАЛЬНОЇ АКАДЕМІЇ МЕДИЧНИХ НАУК УКРАЇНИ", ХАРКІВ, УКРАЇНА

Вступ. Легка закрита черепно-мозкова травма (ЗЧМТ) призводить до розвитку різноманітних 
порушень метаболічних процесів, що відіграють певну роль у розвитку її віддалених наслідків. 

Метою роботи було вивчення аналізу активності деяких маркерних мембрано-зв’язаних ферментів, 
що приймають участь у різних окислювально-відновлювальних реакціях, метаболічних та енергетичних 
процесах.

Методи. У сорока семи хворих із віддаленими наслідками легкої ЗЧМТ та тридцяти здорових осіб 
були проведені обстеження та визначення активності аланінамінотрансферази, аспартатамі-
нотрансферази, лужної фосфатази та лактатдегідрогенази (ЛД) у сироватці крові хроматографічним 
та колорометричним методами.

Результати. Дане дослідження виявило значущі зміни вмісту лужної фосфатази та ЛД, які є 
маркерами ушкодження клітинних мембран, важкості ацидозу, роз’єднання окислювально-
відновлювальних процесів та порушення енергетичного обміну у клітинах. Середній рівень ЛД був 
662,7 МО/л vs 381,9 МО/л у контролі. Виявлене збільшення рівню ЛД прямо пропорційно корелювало з 
прогресуванням захворювання, досягаючи найбільш значущих змін у групі хворих з тривалістю 
захворювання більш 15 років (mean±SD 144,6±16,3 МО/л vs 82,6±8,4 МО/л; p<0,05). Віддалені наслідки після 
перенесеної легкої ЗЧМТ також характеризувалися статистично значущим зниженням активності 
лужної фосфатази (p<0.05) та позитивною кореляційною залежністю (r=+0.48) від тривалості 
посттравматичного періоду, при цьому загальний рівень лужної фосфатази був 152,5±11,21 МО/л vs 
212,6±9,63 МО/л у здорових (p<0,01). Ступінь вираженості змін активності мембрано-зв’язаних 
ферментів був пов’язаний з розвитком оксидативного стресу та дисметаболічних процесів.

Висновки. У хворих з віддаленими наслідками легкої ЗЧМТ було виявлено дисрегуляцію фермен-
тативних процесів, що є маркером порушення різних видів енергетичного обміну у нервової системі 
та деструкції клітинних мембран.

КЛЮЧОВІ СЛОВА: віддалені наслідки; легка закрита черепно-мозкова травма; мембрано-
зв’язані ферменти; метаболічні процеси.

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Інформація про автора
Євгенія Лєкомцева – канд. мед. наук, провідний науковий співробітник відділення функціональної 

нейрохірургії з групою патоморфології, лікар­невропатолог, лікар­психіатр, Державна установа 
“Інститут неврології, психіатрії та наркології Національної академії медичних наук України”, вул. 
Академіка Павлова, 46, 61068, м. Харків

Information about the author 
Yevgeniya Lekomtseva, MD, Ph.D., State Institute of Neurology, Psychiatry and Narcology of the 

National Academy of Medical Sciences of Ukraine, Department of Neurology, Department of Functional 
Neurosurgery and Paroxysmal States, 46 Academic Pavlov Str, Kharkiv, 61068, Ukraine.

ORCID 0000­0003­0961­1636, e­mail: yevgeniyalekomtseva@gmail.com

References
1. Bazan NG. Second messengers derived from 

excitable membranes are involved in ischemic and 
seizure-related brain damage. Patologicheskaia 
fiziologiia i eksperimental'naia terapiia. 1992(4):11­6.

2. Brigode W, Cohan C, Beattie G, Victorino G. 
Alcohol in traumatic brain injury: toxic or therapeutic?. 
Journal of surgical research. 2019 Dec 1;244:196­204.

doi.org/10.1016/j.jss.2019.06.043
3. Brownlee M. Biochemistry and molecular cell 

biology of diabetic complications. Nature. 2001 
Dec;414(6865):813­20.

doi: 10.1038/414813a
4. Halliwell B, Gutteridge JC. Lipid peroxidation, 

oxygen radicals, cell damage, and antioxidant 
therapy. The Lancet. 1984 Jun 23;323(8391):1396­7.

5. Huang XJ, Choi YK, Im HS, Yarimaga O, Yoon E, 
Kim HS. Aspartate aminotransferase (AST/GOT) and 
alanine aminotransferase (ALT/GPT) detection 
techniques. Sensors. 2006 Jul;6(7):756­82.

doi: 10.3390/s6070756
6. Jenner P. Oxidative damage in neurodege ne-

rative disease. The Lancet. 1994 Sep 17;344(8925): 
796-8.

doi: 10.1016/S0140­6736(94)92347­7
7. Lanni A, Moreno M, Lombardi A, de Lange P, 

Goglia F. Control of energy metabolism by iodo-
thyronines. Journal of Endocrinological Investigation. 
2001 Dec 1;24(11):897­913.

doi: 10.1007/BF03343949
8. Linden DE. The P300: where in the brain is it 

produced and what does it tell us?. The Neuroscientist. 
2005 Dec;11(6):563­76.

doi: 10.1177/1073858405280524
9. Lekomtseva Y, Voloshyn-Gaponov I, Tatayna G. 

Targeting Higher Levels of Tau Protein in Ukrainian 
Patients with Wilson’s Disease. Neurology and 
therapy. 2019 Jun 1;8(1):59­68.

doi: 10.1007/s40120­019­0134­3
10. Mayer EA, Fanselow MS. Dissecting the 

components of the central response to stress. Nature 
Neuroscience. 2003 Oct;6(10):1011­107.

doi: 10.1038/nn1003­1011
11. McGinn MJ, Povlishock JT. Pathophysiology 

of traumatic brain injury. Neurosurgery Clinics. 2016 
Oct 1;27(4):397­407.

doi: 10.1016/j.nec.2016.06.002

12. Neuberger EJ, Abdul Wahab R, Jayakumar A, 
Pfister BJ, Santhakumar V. Distinct effect of impact 
rise times on immediate and early neuropathology 
after brain injury in juvenile rats. Journal of neuro-
science research. 2014 Oct;92(10):1350­61.

doi: 10.1002/jnr.23401
13. Phillips LL, Lyeth BG, Hamm RJ, Povlishock JT. 

Combined fluid percussion brain injury and entor­
hinal cortical lesion: a model for assessing the inter­
action between neuroexcitation and deafferentation. 
Journal of neurotrauma. 1994 Dec;11(6):641­56.

doi: 10.1089/neu.1994.11.641
14. Phillips LL, Lyeth BG, Hamm RJ, Reeves TM, 

Povlishock JT. Glutamate antagonism during se con-
dary deafferentation enhances cognition and axo‐
dendritic integrity after traumatic brain injury. 
Hippo campus. 1998;8(4):390­401.

doi: 10.1002/(SICI)1098­1063(1998)8:4<390::AID­
HIPO7>3.0.CO;2­L

15. Phillips LL, Reeves TM. Interactive pathology 
following traumatic brain injury modifies hippo­
campal plasticity. Restorative neurology and neuro-
science. 2001 Jan 1;19(3, 4):213­35.

16. Pryor WA. Free radicals and lipid peroxidation: 
what they are and how they got that way. Natural 
antioxidants in human health and disease. 1994 Jan 
1:1­24.

doi: 10.1016/B978­0­08­057168­3.50007­2
17. Rattan SI. Theories of biological aging: genes, 

proteins, and free radicals. Free radical research. 
2006 Jan 1;40(12):1230­8.

doi: 10.1080/10715760600911303
18. Sohal RS. Role of oxidative stress and protein 

oxidation in the aging process. Free Radical Biology 
and Medicine. 2002 Jul 1;33(1):37­44.

doi: 10.1016/S0891­5849(02)00856­0
19. Zhang P, Wang CY, Li YX, Pan Y, Niu JQ, He SM. 

Determination of the upper cut-off values of serum 
alanine aminotransferase and aspartate amino-
transferase in Chinese. World Journal of Gastro-
enterology: WJG. 2015 Feb 28;21(8):2419­24.

doi: 10.3748/wjg.v21.i8.2419
20. Zhang J, Shi C, Wang H, Gao C, Chang P, 

Chen X, Shan H, Zhang M, Tao L. Protective Effects 
of Hydrogen Sulfide on a Cell Culture Model of Trau­
matic Scratch Injury involving Suppression of Oxi-

ye. Lekomtseva



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E

ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2

dative Stress and Upregulation of Nrf-2. The interna-
tional journal of biochemistry & cell biology. 2019 
Oct:105636.

doi: 10.1016/j.biocel.2019.105636
21. Zhang QH, Hao JW, Xiao-Jing J, Guang-Lei L, 

Zhou M, Yao YM. Long-lasting neurobehavioral 
alterations in burn-injured mice resembling post-

traumatic stress disorder in humans. Experimental 
neurology. 2019 Nov:113084­.

doi: 10.1016/j.expneurol.2019.113084
22. Zhou YF, Li WT, Han HC, Gao DK, He XS, Li L, 

Song JN, Fei Z. Allicin protects rat cortical neurons 
against mechanical trauma injury by regulating nitric 
oxide synthase pathways. Brain research bulletin. 
2014 Jan 1;100:14­21.

doi: 10.1016/j.brainresbull.2013.10.013

Received 03 October 2019; revised 1 November 2019; 
accepted 13 November 2019.

This is open access article distributed under the Creative Com-
mons Attribution License, which permits unrestricted use, 
distribution, and reproduction in any medium, provided the 
original work is properly cited.

ye. Lekomtseva