Dissertation > Excellent graduate degree dissertation topics show

Poloxamer188Suppresses Apoptosis and Activating Autophagy on Mice Traumatic Brain Injury Model

Author: BaoHaiJun
Tutor: TaoLuYang
School: Suzhou University
Course: Forensic
Keywords: traumatic brain injury Poloxamer188 apoptosis autophagy
CLC: D919.1
Type: PhD thesis
Year: 2012
Downloads: 13
Quote: 0
Read: Download Dissertation

Abstract


Objective:It has been reported that the loss in cell membrane integrity is a major contributor to the development of neuronal damage subsequent to traumatic brain injury (TBI). Our previous study has showed that TBI causes increasing of neural cell apoptosis and autophagy, and resealing of disrupted plasma membranes is a criticality therapeutic strategy for TBI. But the mechanism of rescue the subsequent damaged neuron in TBI after cell membrane integrity recovery remains elusive. Here, we utilized a copolymer membrane sealant, Poloxamer188(P188), to investigate whether the apoptosis and autophagy involve in the mechanism of rescuing cell death in our mice TBI model.Methods:Mice TBI model was established by weight drop device in adult mice based on procedures previously reported. P188was administered with tail intravenous injection after TBI. Mice were pretreated with intraperitoneal injection of propidium iodide (PI)1h before sacrificed. PI-labeling was used to identify injured cells, and the amount of PI positive cells was counted. Furthermore, the cumulative loss of brain tissue was determined to explore whether PI-positive cells could represent TBI-induced cell lost. Finally, motor test and Morris water maze were performed for detecting whether TBI-induced cell loss would result in behavior deficits. We examined the levels of apoptosis associate proteins, and the protein levels of LC-3, beclin-1,P-Akt, hVps34were also detected.Results:(1) PI-positive cells were found in all groups that surffered TBI. The number of PI-positive cells peaked in the24h time-point group, and P188treatment significantly decreased the number of PI-positive cells.(2) Compared with saline vehicle groups, P188treatment markedly reduced lesion volume and behavioral deficits which induced by TBI.(3) An elevated activated caspase-3, bax and P53protein levels were detected after TBI, but the elevation were suppressed by P188treatment. However, Bcl-2protein levels were up-regulated by P188. To further explore the mechanism of P188reduces apoptosis, cyt-c, caspase-8, caspase-9protein levels were also assessed by Western-bloting after TBI. The TBI induced up-regulation of cyt-c, caspase-8, and caspase-9protein levels were also reversed by P188.(4) Microtubule-associated protein light chain3(LC3Ⅱ) was up-regulated after TBI in P188treatment groups when compared with saline vehicle groups. To further investigate the mechanism of P188increases autophagy, P62, hVps34and Beclin-1protein levels were assessed. Compared with saline vehicle groups, P62level was significantly decreased vs. Vps34and Beclin-1remarkably increased in P188treatment groups.Conclusion:(1) P188remarkably attenuated TBI-induced neural cell death, lesion volume, and motor and cognitive dysfunction.(2) P188reduced TBI induced apoptosis through both extrinsic and intrinsic pathway.(3) Autophagy is activated by P188treatment after TBI. P188promoted autophagy activation may rescue the subsequent damaged cells from death following TBI.

Related Dissertations

  1. The Study on Cryopreservation and Mechanism of Freezing Injury on the Spermatozoa of Coelomactra Antiquate,S968.3
  2. The Study of Lead Exposure on Cyprinus Carpio Ovary Epithelial Cells,X174
  3. Effects of Diclazuril on G3PDH in Second-generation Merozoites of Eimeria Tenella,S858.31
  4. The Effects and Preliminary Study of PCV2 on Ca2+ Signal in Lymphocytes of Piglets,S858.28
  5. Effects of Angiogenic Factor on Follicular Angiogenesis and Development in Sexual Maturity Mice,S852.2
  6. Expression of β-Catenin in Pig’s Ovary and the Effect of β-Catenin on Porcine Granulosa Cells Apotosis and Steroidogenesis Related Enzyme,S828
  7. Induced Combination Apoptosis by FB1 and AFB1 in Vero Cell,S856.9
  8. The Apoptosis Mechanism Induced by Aflatoxin B1 and Deoxynivalenol in Primary Hepatocyte of Cyprinus Carpio,S856.9
  9. Effects of BMPR-IB Gene Silencing by Small Interfering RNA on Apoptosis of Porcine Pollicular Granulosa Cells and Ecpression of BMP Pathy-Way-Ralted Genes,S828
  10. The Effects of Don on Proliferation, Differentiation, and Apoptosis of Chondrocytes in Chicken,S858.31
  11. The Effect of Foxol on Apoptosis of Mouse Granule Cells,S865.13
  12. The Signal Mechanism Underlying DON Induced Apoptosis in BHK-21 Cells,S856.9
  13. The Expression and Mechanism of NF-κ B and IL-6 after 90% Portal Vein Ligation in Rats,R657.3
  14. The Impact of Histone Deacetylase Inhibitor Trichostatin a on Proliferation and Apoptosis of Porcine Granulosa Cells,S828
  15. Therapeutic Effect and Mechanisms of Derived Mesenchymal Stem Cells in Intracerebral Hemorrhage Rat,R743.34
  16. Effects of Different Immunization on the Development of Immune Organs,cell Proliferation and Expression of Apoptosis-relatived Gene in Chicken,S858.31
  17. The Neuroprotective Effect of Z-ligustilide Against Oxidative Stress Induced by D-galactose and Hydrogen Peroxide,R285.5
  18. The Effect of Mild Hypothermia Combined with TP-5 to T Lymphocyte Subsets and Prognosis of Patients with Severe Traumatic Brain Injur,R651.15
  19. Expression of Caspase-4 and Caspase-3 Gene Related Apoptosis in Pathological Changes of Sternocleidomastoid of Congenital Muscular Torticollis and Four Years Clinical Followed-up for Opereated Patients,R726.8
  20. The Expression Mechanism of Calmodulin in Rat with Brain Contusion,R651.1
  21. The Relevance Research of Neuroglobin and Caspase-3 in the Hippocampus CA1 Regin in Global Cerebral Ischemia-reperfused Rats,R741

CLC: > Political, legal > Legal > UNIVERSITY > Forensic > Forensic basic science
© 2012 www.DissertationTopic.Net  Mobile