Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage

Yisi LIAO; Jiashang HUANG; Yanfeng XIE; Quanhong SHI; Wei DAN; Li JIANG; Yi XIANG; Kuan WANG; Yan ZHAN

doi:10.16016/j.2097-0927.202202166

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Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage

Basic Medicine | 更新时间：2026-01-09

- Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage
- Journal of Army Medical University Vol. 44, Issue 12, Pages: 1243-1248(2022)
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院神经外科
- 作者简介：
- 基金信息：
  
  the General Program of Natural Science Foundation of Chongqing(cstc2015jcyjA10077)
- DOI：10.16016/j.2097-0927.202202166
  CLC： R363.21;R651.15;R743.35
- Received：28 February 2022，
  
  Revised：2022-03-08，
  
  Published：30 June 2022
- 稿件说明：
移动端阅览
Yisi LIAO, Jiashang HUANG, Yanfeng XIE, et al. Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage[J]. Journal of Army Medical University, 2022, 44(12): 1243-1248.
DOI：

Yisi LIAO, Jiashang HUANG, Yanfeng XIE, et al. Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage[J]. Journal of Army Medical University, 2022, 44(12): 1243-1248. DOI： 10.16016/j.2097-0927.202202166.

摘要

目的

观察蛛网膜下腔出血(subarachnoid hemorrhage，SAH)后抑制血小板源性生长因子受体(platelet-derived growth factor receptor，PDGFR)活化及活性氧(reactive oxygen species，ROS)对早期脑损伤(Early brain injury，EBI)的作用，探讨它们影响SAH后早期脑损伤的可能机制。

方法

将成年雄性SD大鼠随机分为假手术组、SAH组、PDGF受体抑制组和ROS抑制组，每组12只。通过血管内穿刺法建立大鼠SAH模型，1 h后，治疗组动物通过腹腔注射相应的药物。在术后24、48 h，统计动物死亡率、体质量变化、神经行为学评分评估大脑功能障碍，测定脑含水量评估血脑屏障通透性。采用Western blot检测PDGFR及其磷酸化产物变化情况以及SAH后磷酸化JNK、MMP-9的表达。分别检测脂质和蛋白的氧化产物MDA含量和ROS水平。

结果

抑制PDGFR的激活、清除ROS都能使SAH后脑含水量降低(

0.05)，减少MMP-9表达(

0.05)，改善神经功能评分(

0.05)，减少ROS及MDA产生(

0.05)，减少JNK和c-Jun的磷酸化JNK和c-Jun的磷酸化。抑制ROS的生成能在一定程度上减少PDGFR的激活，抑制PDGFR的激活也能在一定程度上减少ROS的产生(

0.05)。

结论

大鼠蛛网膜下腔出血后，ROS参与了PDGFR的激活，PDGFR激活能进一步加重自由基损伤。JNK-MMP-9途径是早期脑损伤中引起血脑屏障破坏的重要途径。

Abstract

Objective

To investigate the effects of inhibiting the activation of platelet-derived growth factor receptor (PDGFR) and reactive oxygen species (ROS) on early brain damage (EBI) after subarachnoid hemorrhage (SAH)

and explore their possible acting mechanism in the process.

Methods

Adult male SD rats were randomly divided into sham operation group

SAH group

PDGF receptor inhibition group and ROS inhibition group

with 12 rats in each group. The rat model of SAH was established by intravascular puncture. In 1 h later

the rats in the treatment groups were injected with corresponding drugs by intraperitoneal injection. At 24 and 48 h after operation

animal mortality and body weight changes were observed

brain dysfunction was evaluated with neurobehavioral assessment

and brain water content was measured to evaluate blood-brain barrier permeability. Western blot analysis was used to detect the changes of PDGFR and phosphorylated PDGFR and the expression of p-JNK and p-MMP-9 after SAH. The oxidation products of lipids and proteins

malondialdehyde (MDA) and ROS were also detected.

Results

Both inhibiting the activation of PDGFR and scavenging ROS reduced brain water content after SAH (

0.05)

decreased the expression of MMP-9 (

0.05)

improved the neurological function score (

0.05)

reduced the production of ROS and MDA (

0.05)

and decreased the phosphorylation of JNK and c-Jun. Inhibiting the generation of ROS suppressed the activation of PDGFR to a certain extent

and inhibiting the activation of PDGFR also reduced the generation of ROS to a certain extent (

0.05).

Conclusion

After SAH in rats

ROS is involved in the activation of PDGFR

and its activation can further aggravate free radical damage. The JNK-MMP-9 pathway is indeed an important pathway that causes blood-brain barrier disruption in EBI.

关键词

Keywords

references

PAPADOPOULOS N, LENNARTSSON J. The PDGF/PDGFR pathway as a drugtarget[J]. Mol Aspects Med, 2018, 62: 75-88. DOI: 10.1016/j.mam.2017.11.007.

LOVELOCK C E, RINKEL G J E, ROTHWELL P M. Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review[J]. Neurology, 2010, 74 (19): 1494-1501. DOI: 10.1212/WNL.0b013e3181dd42b3.

CONTRERAS O, CÓRDOVA-CASANOVA A, BRANDAN E. PDGF-PDGFR network differentially regulates the fate, migration, proliferation, and cell cycle progression of myogenic cells[J]. Cell Signal, 2021, 84: 110036. DOI: 10.1016/j.cellsig.2021.110036.

YANG P, MANAENKO A, XU F, et al . Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model[J ] . Exp Neurol, 2016, 283(Pt A): 157-164. DOI: 10.1016/j.expneurol.2016.06.010.

ZHAN Y, CHEN C H, SUZUKI H, et al . Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats[J ] . Crit Care Med, 2012, 40(4): 1291-1296. DOI: 10.1097/CCM.0b013e31823da96d.

ZHAN Y, KRAFFT P R, LEKIC T, et al . Imatinib preserves blood-brain barrier integrity following experimental subarachnoid hemorrhage in rats[J ] . J Neurosci Res, 2015, 93(1): 94-103. DOI: 10.1002/jnr.23475.

秦媛媛. NADPH和NOX抑制剂Apocynin(夹竹桃麻素)联用在小鼠脑卒中模型中抗炎和神经保护的作用[D]. 苏州: 苏州大学, 2017.

QIN Y Y. Anti-inflammatory and neuroprotective effects of combined NADPH and the NOX inhibitor apocynin in a mouse model of stroke[D]. Suzhou: Soochow University, 2017.

KOBAYASHI K, ARAYA J, MINAGAWA S, et al . Involvement of PARK2-mediated mitophagy in idiopathic pulmonary fibrosis pathogenesis[J ] . J Immunol, 2016, 197(2): 504-516. DOI: 10.4049/jimmunol.1600265.

CHEN C H, MANAENKO A, ZHAN Y, et al . Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model[J ] . Neuroscience, 2010, 169(1): 402-414. DOI: 10.1016/j.neuroscience.2010.04.043.

NEIFERT S N, CHAPMAN E K, MARTINI M L, et al . Aneurysmal subarachnoid hemorrhage: the last decade[J ] . Transl Stroke Res, 2021, 12(3): 428-446. DOI: 10.1007/s12975-020-00867-0.

GERAGHTY J R, DAVIS J L, TESTAI F D. Neuroinflammation and microvascular dysfunction after experimental subarachnoid hemorrhage: emerging components of early brain injury related to outcome[J]. Neurocrit Care, 2019, 31(2): 373-389. DOI: 10.1007/s12028-019-00710-x.

RASS V, HELBOK R. Early brain injury after poor-grade subarachnoidhemorrhage[J]. Curr Neurol Neurosci Rep, 2019, 19(10): 78. DOI: 10.1007/s11910-019-0990-3.

HAYMAN E G, WESSELL A, GERZANICH V, et al . Mechanisms of global cerebral edema formation in aneurysmal subarachnoid hemorrhage[J ] . Neurocrit Care, 2017, 26(2): 301-310. DOI: 10.1007/s12028-016-0354-7.

ZHANG Z Y, FANG Y J, LENAHAN C, et al . The role of immune inflammation in aneurysmal subarachnoid hemorrhage[J ] . Exp Neurol, 2021, 336: 113535. DOI: 10.1016/j.expneurol.2020.113535.

MUNDT S, GRETER M, FLVGEL A, et al . The CN S immune landscape from the viewpoint of a T cell[J ] . Trends Neurosci, 2019, 42(10): 667-679. DOI: 10.1016/j.tins.2019.07.008.

BENNETT M, CHIN A, LEE H J, et al . Proteoglycan 4 reduces neuroinflammation and protects the blood-brain barrier after traumatic brain injury[J ] . J Neurotrauma, 2021, 38(4): 385-398. DOI: 10.1089/neu.2020.7229.

WU C, HU Q, CHEN J Y, et al . Inhibiting HIF-1α by 2ME2 ameliorates early brain injury after experimental subarachnoid hemorrhage in rats[J ] . Biochem Biophys Res Commun, 2013, 437(3): 469-474. DOI: 10.1016/j.bbrc.2013.06.107.

BALL S G, SHUTTLEWORTH C A, KIELTY C M. Vascular endothelial growth factor can signal through platelet-derived growth factorreceptors[J]. J Cell Biol, 2007, 177(3): 489-500. DOI: 10.1083/jcb.200608093.

WAN W F, DING Y, XIE Z Y, et al . PDGFR-β modulates vascular smooth muscle cell phenotype via IRF-9/SIRT-1/NF-κB pathway in subarachnoid hemorrhage rats[J ] . J Cereb Blood Flow Metab, 2019, 39(7): 1369-1380. DOI: 10.1177/0271678x18760954..

KURITA Y, ARAYA J, MINAGAWA S, et al . Pirfenid one inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy[J ] . Respir Res, 2017, 18(1): 114. DOI: 10.1186/s12931-017-0600-3.

AOMATSU E, CHOSA N, NISHIHIRA S, et al . Cell-cell adhesion through N-cadherin enhances VCAM-1 expression via PDGFRβ in a ligand-independent manner in mesenchymal stem cells[J ] . Int J Mol Med, 2014, 33(3): 565-572. DOI: 10.3892/ijmm.2013.1607.

FRIJHOFF J, DAGNELL M, AUGSTEN M, et al . The mitochondrial reactive oxygen species regulator p66Shc controls PDGF-induced signaling and migration through protein tyrosine phosphatase oxidation[J ] . Free Radic Biol Med, 2014, 68: 268-277. DOI: 10.1016/j.freeradbiomed.2013.12.022.

TAO T, LIU G J, SHI X, et al . DHEA attenuates microglial activation via induction of JMJD3 in experimental subarachnoid haemorrhage[J ] . J Neuroinflammation, 2019, 16(1): 243. DOI: 10.1186/s12974-019-1641-y..

PENG Y C, ZHUANG J F, YING G Y, et al . Stimulator of IFN genes mediates neuroinflammatory injury by suppressing AMPK signal in experimental subarachnoid hemorrhage[J ] . J Neuroinflammation, 2020, 17(1): 165. DOI:10.1186/s12974-020-01830-4.

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