Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (4): 708-714. doi: 10.19723/j.issn.1671-167X.2024.04.026

Previous Articles     Next Articles

Correlations between serum BDNF, IL-18 and hs-CRP levels in patients with acute cerebral infarction and vascular cognitive impairment

Jinna LI1,Li' na XU1,Min LI1,Yi SONG2,Jing ZHANG2,Longbin JIA1,*()   

  1. 1. Department of Neurology, Jincheng People' s Hospital, Jincheng 048000, Shanxi, China
    2. Graduate Institute of Changzhi Medical College, Changzhi 046000, Shanxi, China
  • Received:2021-09-26 Online:2024-08-18 Published:2024-07-23
  • Contact: Longbin JIA E-mail:1518205918@qq.com
  • Supported by:
    the Key Prevention and Control Projects of Major Chronic Non-communicable Disease of the National Key Research and Development Program(2017YFC1310001);the Jincheng People' s Hospital project(JSY-2021G006)

RICH HTML

  

Abstract:

Objective: To explore the correlations between serum levels of brain-derived neurotrophic factor (BDNF), interleukin-18 (IL-18) and hypersensitivity C-reactive protein (hs-CRP) in patients with acute cerebral infarction and vascular cognitive impairment (VCI), and to provide some clinical bases for early prevention of VCI. Methods: A total of 160 patients with acute cerebral infarction admitted in Department of Neurology of Jincheng People' s Hospital from May 2019 to April 2020 were enrolled in this study and were devided into three groups according to whether or not combined with cognitive impairment, including no cognitive impairment group (NCI, 57 cases), vascular cognitive impairment no dementia group (VCIND, 56 cases) and vascular dementia group (VaD, 47 cases). The cognitive function of all the patients were evaluated by Montreal cognitive assessment (MoCA). The National Institute of Health stroke scale (NIHSS) was used to assess the degree of neurological deficit (mild-, moderate-, severe-neurologic deficit group). The infarct size was calculated by Pullicino' s method (small-, middle-, large-infarct group). The levels of serum BDNF and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), and serum levels of hs-CRP were measured by immunoturbidimetry during the acute phase (0-7 d), recovery period (15-30 d) and 6 months after cerebral infarction. The effects of varying degrees of neurological deficits and different size of infarction on BDNF, IL-18 and hs-CRP were observed. The levels of serum BDNF, IL-18 and hs-CRP in the patients of the three groups with acute, convalescent and six-month cerebral infarction were compared, and their correlations with VCI were analyzed. Results: Serum BDNF level and MoCA scores in mild-neurologic deficit group and small-infarct group were significantly higher than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). Their levels of IL-18 and hs-CRP were significantly lower than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). The levels of serum BDNF in NCI group, VCIND group and VaD group during the acute phase, convalescence and 6 months after cerebral infarction were in a significant decline, and the differences during the acute phase and recovery period were statistically significant (P < 0.05). The levels of IL-18 and hs-CRP during the acute phase, recovery period and 6 months after cerebral infarction showed a significant increasing trend with significance (P < 0.05). Correlation analysis revealed that the levels of BDNF was positively correlated with MoCA scores but negatively correlated with the severity of cognitive impairment while the expression levels of IL-18 and hs-CRP were negatively correlated with MoCA scores but positively correlated with the severity of cognitive impairment. Conclusion: Serum BDNF, IL-18 and hs-CRP are involved in the pathological process of occurrence and development of VCI in the patients with acute cerebral infarction. BDNF has a protective effect on VCI while IL-18 and hs-CRP cause severe cognitive impairment. The levels of serum BDNF、IL-18 and hs-CRP in the patients with acute ischemic cerebral infarction are closely related to the severity of cognitive impairment and can be used as biomarkers of early diagnosis of VCI.

Key words: Brain infarction, Vascular cognitive impairment, Brain-derived neurotrophic factor, Interleukin-18, Hypersensitivity C-reactive protein

CLC Number: 

  • R749.13

Table 1

Comparison of general indexes among three groups"

Research indexes NCI group (n=57) VCIND group (n=56) VaD group (n=47) χ2/F P
Gender (male), n (%) 35 (61.4) 32 (57.1) 28 (59.6) 0.214 0.899
Age/ years, $\bar x \pm s$ 62.93±7.54 64.33±7.78 65.02±8.86 2.170 0.446
Years of education, $\bar x \pm s$ 8.62±3.04 8.41±3.17 7.97±2.88 1.684 0.831
Smoking, n (%) 11 (19.3) 18 (32.1) 19 (40.4) 5.164 0.059
Drinking, n (%) 14 (24.6) 12 (21.4) 14 (29.8) 0.961 0.618
Hypertension, n (%) 16 (28.1) 19 (33.9) 19 (40.4) 1.402 0.496
Diabetes, n (%) 10 (17.5) 11 (19.6) 13 (27.7) 1.708 0.426
Hyperlipemia, n (%) 11 (19.3) 13 (23.2) 15 (31.9) 2.287 0.319
History of stroke, n (%) 12 (21.1) 16 (28.6) 17 (36.2) 2.230 0.328
NIHSS, M (P25, P75) 1 (1, 4) 1 (1, 4) 2 (1, 4) 2.228 0.033
Classification of cerebral infarction, n (%)
  Partial anterior Circulation infarction 16 (28.07) 16 (28.57) 12 (25.53) 0.237 0.751
  Subcortical infarction 29 (50.88) 27 (48.21) 23 (48.94) 0.316 0.584
  Posterior circulation infarction 12 (21.05) 13 (23.21) 12 (25.53) 0.441 0.528
Infarct area, n (%)
  Large infarct 0 (0) 8 (14.29) 20 (42.55) 7.153 0.014
  Middle infarct 3 (8.77) 34 (60.71) 18 (38.30) 6.278 0.026
  Small infarct 54 (94.74) 14 (25.00) 9 (19.15) 7.144 0.034

Table 2

BDNF, IL-18 and hs-CRP levels and MoCA scores in the patients with different neurological deficits and infarct size during acute phase"

ItemsNeurologic deficit group Infarct area group
Mild (n=82) Moderate (n=52) Severe (n=26) F P Small (n=77) Middle (n=55) Large (n=28) F P
BDNF/(μg/L) 5.66±2.48ab 4.89±2.33a 3.71±2.62 14.152 0.031 5.78±1.61cd 5.02±2.07c 3.55±1.43 14.761 0.028
IL-18/(ng/L) 27.57±2.94ab 43.57±3.45a 64.57±4.83 15.184 0.024 23.57±1.94cd 38.87±4.65c 68.50±5.39 16.214 0.019
hs-CRP/(mg/L) 5.95±2.63ab 11.73±4.04a 24.32±6.76 18.393 0.013 5.67±1.48cd 13.16±3.54c 26.08±7.79 23.545 0.009
MoCA scores 24.57±1.94ab 15.44±2.11a 10.35±3.25 11.267 0.037 25.70±2.26cd 16.73±2.48c 9.89±3.16 13.376 0.033

Table 3

Comparison of BDNF, IL-18 and hs-CRP expression levels among the three groups"

Groups nAcute phase Convalescence period At 6 months
BDNF/(μg/L) IL-18/(ng/L) hs-CRP/(mg/L) BDNF/(μg/L) IL-18/(ng/L) hs-CRP/(mg/L) BDNF/(μg/L) IL-18/(ng/L) hs-CRP/(mg/L)
NCI group 57 5.74±2.52a 27.92±4.84ab 3.02±0.88ab 6.62±2.46a 13.25±2.13ab 2.84±0.55ab 4.36±1.37 8.67±2.25ab 2.53±0.62ab
VCIND group 56 5.03±2.11a 56.85±6.61a 9.23±2.14a 5.47±2.19a 38.16±4.24a 6.19±2.02a 4.03±1.45 14.19±1.97a 4.47±1.29a
VaD group 47 3.67±0.79 76.68±5.89 18.14±7.52 3.81±0.56 49.38±3.77 13.46±6.20 3.14±0.37 20.66±3.46 9.92±5.77
F 15.045 16.757 19.884 24.671 15.466 13.881 1.664 8.787 10.176
P 0.033 0.027 0.019 0.001 0.029 0.020 0.173 0.041 0.026

Table 4

Correlation analysis of serum factors levels and MoCA scores among the three groups"

ItemsNCI group VCIND group VaD group
r P r P r P
BDNF 0.822 <0.01 0.796 <0.01 0.842 <0.01
IL-18 -0.741 <0.01 -0.761 <0.01 -0.713 <0.01
hs-CRP -0.778 <0.01 -0.729 <0.01 -0.686 <0.01

Table 5

Multivariate Logistic regression analysis of risk of VCI in the patients with acute cerebral infarction"

Items Standard error Wald P Odds ratio 95%CI
Infarct area 0.075 4.52 0.033 2.830 0.982-3.428
NIHSS 0.042 7.66 0.010 3.437 1.226-4.271
BDNF 0.029 5.71 0.067 1.826 1.698-2.567
IL-18 0.061 6.13 0.016 1.171 0.977-3.685
hs-CRP 0.016 4.42 0.004 1.357 2.446-6.997
1 Dichgans M , Leys D . Vascular cognitive impairment[J]. Circ Res, 2017, 120 (3): 573- 591.
doi: 10.1161/CIRCRESAHA.116.308426
2 Kim JH , Chon D . Association between cognitive impairment, vascular disease and all-cause mortality[J]. J Nutr Health Aging, 2018, 22 (7): 790- 795.
doi: 10.1007/s12603-018-1011-y
3 Teng Z , Dong Y , Zhang D , et al. Cerebral small vessel disease and post-stroke cognitive impairment[J]. Int J Neurosci, 2017, 127 (9): 824- 830.
doi: 10.1080/00207454.2016.1261291
4 Binsimon K , Herrmann N , Swardfager W , et al. Kynurenine and depressive symptoms in a post stroke population[J]. Neuropsychiatr Dis Treat, 2014, 10 (2): 1827- 1835.
5 Hovens IB , Schoemaker RG , van der Zee EA , et al. Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning[J]. Brain Behav Immun, 2014, 38 (3): 202- 210.
6 An XL , Li CL . Analysis of risk factors for vascular cognitive impairment in patients with cerebral infarction[J]. Cell Biochem Biophys, 2015, 71 (2): 673- 677.
doi: 10.1007/s12013-014-0246-4
7 国家卫生计生委脑卒中防治工程委员会, 脑卒中防治系列指导规范编审委员会. 2016中国血管性认知障碍诊疗指导规范[J]. 心脑血管病防治, 2017, 217 (1): 13- 16.
8 First MB . Diagnostic and statistical manual of mental disorders, 5th edition, and clinical utility[J]. J Nervous Mental Disease, 2013, 201 (9): 727- 729.
doi: 10.1097/NMD.0b013e3182a2168a
9 Zhao XJ , LI QX , Liu TJ , et al. Predictive values of CSS and NIHSS in the prognosis of patients with acute cerebral infarction: A comparative analysis[J]. Medicine, 2018, 97 (39): e12419.
doi: 10.1097/MD.0000000000012419
10 Pullicino P . Small deep infarcts diagnosed on computed tomograohy[J]. Neurology, 1980, 30 (10): 1090- 1096.
doi: 10.1212/WNL.30.10.1090
11 周琪, 张玉敏, 顾全, 等. 脂蛋白a、N-末端脑钠肽前体和白细胞计数联合检测在脑卒中诊断中的应用价值[J]. 标记免疫分析与临床, 2017, 24 (3): 267- 270.
12 郭丽, 宋国强, 赵宗茂, 等. 胰岛素样生长因子-1体外诱导人脐带间充质干细胞向神经样细胞分化[J]. 中华实验外科杂志, 2016, 33 (6): 1589- 1592.
13 于永华, 韩骐, 唐茂庆. 急性缺血性脑卒中患者认知障碍情况及影响因素分析[J]. 四川解剖学杂志, 2019, 9 (3): 128- 129.
14 杜杰. 黄芪总苷和人参皂苷降低缺血性脑卒中患者脑脊液中谷氨酸、磷酸化Tau[J]. 东南大学学报(医学版), 2017, 36 (5): 828- 832.
15 Zhang G , Zhang T , Li N , et al. Tetramethylpyrazine nitrone activates the BDNF/Akt/CREB pathway to promote post-ischaemic neuroregeneration and recovery of neurological functions in rats[J]. Br J Pharmacol, 2018, 175 (3): 517- 531.
doi: 10.1111/bph.14102
16 李海龙, 毕晓莹. 小胶质细胞激活介导非特异性炎症在血管性认知障碍白质脱髓鞘损伤机制中的研究进展[J]. 中国卒中杂志, 2015, 10 (9): 771- 777.
17 Lénárt N , Brough D , Dénes A , et al. Inflammasomes link vascular disease with neuroinflammation and brain disorders[J]. J Cereb Blood Flow Metab, 2016, 36 (10): 1668- 1685.
doi: 10.1177/0271678X16662043
18 陈粤瑛, 宋晓楠, 杨树龙. 炎症相关因子在血管性痴呆发病机制中的作用[J]. 中国生物化学与分子生物学报, 2019, 35 (7): 693- 699.
19 Sokolic J , Sotosek Tokmadzic V , Knezevic D , et al. Corrigendum to "Endothelial dysfunction mediated by interleukin-18 in patients with ischemic heart disease undergoing coronary artery bypass grafting surgery"[Med. Hypotheses 104 (2017) 20-24][J]. Med Hypotheses, 2018, 111- 40.
20 Siracusa R , Impellizzeri D , Cordaro M , et al. Anti-inflammatory and neuro-protective efforts of co-ultra PEAlut in a mouse model of vascular dementia[J]. Front Neurol, 2017, 8 (6): 12- 18.
21 Shen D , Tian X , Sang W , et al. Effort of melatonin and resveratrol against memory impairment and hippocampal damage in a rat model of vascular dementia[J]. Neuroimmunomodulation, 2016, 23 (5/6): 318- 331.
22 Civil Arslan F , Tiryaki A , Özkorumak Karagüzel E , et al. The relationship of interleukin-18 and interleukin-6 levels with cognitive functions in bipolar disorder[J]. Turk Psikiyatri Derg, 2017, 28 (2): 81- 88.
23 Wang Z , Meng S , Cao L , et al. Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment[J]. J Neuroinflammation, 2018, 15 (1): 109.
doi: 10.1186/s12974-018-1137-1
24 Janesch P , Rouha H , Badarau A , et al. Assessing the function of pneumococcal neuraminidases NanA, NanB and NanC in invitro and in vivo lung infection models using monoclonal antibo dies[J]. Virulence, 2018, 9 (1): 1521- 1538.
25 Gong P , Liu Y , Huang T , et al. The association between high-sensitivity C-reactive protein at admission and progressive motor deficits in patients with penetrating artery infarctions[J]. BMC Neurol, 2019, 19 (1): 345- 346.
26 Varghese V , Chandra SR , Christopher R , et al. Factors determining cognitive dysfunction in cerebral small vessel disease[J]. Indian J Psychol Med, 2016, 38 (1): 56- 61.
27 柳丰慧, 张可帅. 血清白介素6、基质金属蛋白酶9、基质金属蛋白酶抑制剂1、超敏C反应蛋白及神经生长因子水平与急性脑梗死患者神经功能缺损程度的关系研究[J]. 实用心脑肺血管病杂志, 2017, 25 (1): 35- 38.
[1] YANG Dan, QIAO Lin, ZHAO Li-dan. Cerebral infarction in a patient with primary Sj-gren’s syndrome: a case report and literature review [J]. Journal of Peking University(Health Sciences), 2016, 48(6): 1077-1080.
[2] WANG Yun-yun, SUN Wei, HUANG Yi-ning. Cervical spondylosis misdiagnosed as cerebral infarction: a case report [J]. Journal of Peking University(Health Sciences), 2015, 47(5): 883-884.
[3] HAN Jin-Tao, LI Xuan, ZHENG Mei, FU Jun, WANG Chang-Ming, DONG Guo-Xiang, HE Qing-Yuan. Clinical observation of middle cerebral artery angioplasty in treatment of subcortex cerebral watershed infarction with moderate or severe disabilities [J]. Journal of Peking University(Health Sciences), 2014, 46(4): 606-611.
[4] HU Hao, XU Ke-Xin, ZHANG Xiao-Peng, FANG Zhi-Wei, CHEN Jing-Wen, HUO Fei, WANG Dong, WANG Xiao-Feng. Expression of brainderived neurotrophic factor in urine of patients with benign prostatic hyperplasia  complicated overactive bladder symptoms [J]. Journal of Peking University(Health Sciences), 2014, 46(4): 519-523.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!