Establishment of a hypoxia ischemia reperfusion brain damage model in neonatal rats

Objective: Rice-Vannucci model has been widely used as HIE（Hypoxic ischemic encephalopathy ） animal model in the past forty years, but it does not mimic reperfusion injury that occurs during HIE. The aim of the present study was to establish a new neonatal rat model by simulating hypoxia ischemia reperfusion brain damage (HIRBD) through "common carotid artery (CCA) muscle bridge". Methods: Sixty 7-day-old male Sprague-Dawley rats were randomly assigned to group A (HIRBD groups, n=36), group B (Rice-Vannucci group, n=12), and group C (sham-operated group, n=12). Rats in group A were assigned to 3 subgroups (A1-A3, 12 animals/subgroup). Dynamic changes in cerebral blood flow (CBF) were evaluated by the laser speckle imaging system. The status of the CCA was observed under a stereomicroscope. Changes in body weight, gross morphology as well as pathological sections of brain tissue were examined to evaluate the feasibility of the model. Results: The results indicated that CCA muscle bridge successfully blocked the CBF. CBF was restored after removal of the CCA muscle bridge in HIRBD groups. The CCA was in good condition after removing the muscle bridge, and blood supply was not affected. Changes in body weight, gross morphology and pathological sections of brain tissue indicated that ischemia reperfusion induced by the CCA muscle bridge method caused varying degrees of brain damage. Conclusion: CCA muscle bridge method is effective for establishing a reliable, stable, and reproducible neonatal rat model for study of HIRBD.

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Carnosine pretreatment protects against hypoxia–ischemia brain damage in the neonatal rat model

European Journal of Pharmacology ◽

10.1016/j.ejphar.2011.06.003 ◽

2011 ◽

Vol 667 (1-3) ◽

pp. 202-207 ◽

Cited By ~ 37

Author(s):

Xiangmin Zhang ◽

Lili Song ◽

Xiuyong Cheng ◽

Yi Yang ◽

Bin Luan ◽

...

Keyword(s):

Brain Damage ◽

Rat Model ◽

Neonatal Rat ◽

Hypoxia Ischemia ◽

Neonatal Rat Model

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Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model

European Journal of Pharmacology ◽

10.1016/j.ejphar.2014.01.023 ◽

2014 ◽

Vol 727 ◽

pp. 174-180 ◽

Cited By ~ 8

Author(s):

Huizhen Zhang ◽

Shang Guo ◽

Linlin Zhang ◽

Liting Jia ◽

Zhan Zhang ◽

...

Keyword(s):

Brain Damage ◽

Rat Model ◽

Neonatal Rat ◽

Hypoxia Ischemia ◽

Neonatal Rat Model

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ISDN2014_0189: Sulforaphane is not additive in combination with hypothermia in a neonatal rat model of hypoxia–ischemia

International Journal of Developmental Neuroscience ◽

10.1016/j.ijdevneu.2015.04.155 ◽

2015 ◽

Vol 47 (Part_A) ◽

pp. 55-55 ◽

Cited By ~ 1

Author(s):

Ann‐Marie Przyslupski ◽

Edward Armstrong ◽

Keqin Shen ◽

Jerome Y. Yager

Keyword(s):

Rat Model ◽

Neonatal Rat ◽

Hypoxia Ischemia ◽

Neonatal Rat Model

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Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins

BMC Pediatrics ◽

10.1186/s12887-017-0824-x ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 11

Author(s):

Li-Xiao Xu ◽

Yuan Lv ◽

Yan-Hong Li ◽

Xin Ding ◽

Ying Wang ◽

...

Keyword(s):

Brain Damage ◽

Rat Model ◽

Peripheral Tissue ◽

Neonatal Rat ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Tissue Edema ◽

Related Proteins ◽

Neonatal Rat Model

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Thrombopoietin Has Neural Protective Effect in a Neonatal Rat Model of Hypoxic-Ischemic Brain Damage

Blood ◽

10.1182/blood.v128.22.5059.5059 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5059-5059 ◽

Cited By ~ 1

Author(s):

Mo Yang ◽

Lei Liu ◽

Enyu Liang ◽

Beng H Chong ◽

Chunfu Li

Keyword(s):

Brain Damage ◽

Rat Model ◽

Akt Signaling ◽

Cerebral Hemispheres ◽

Neonatal Rat ◽

Neural Cells ◽

Rt Pcr ◽

Hematopoietic Growth Factors ◽

Neonatal Rat Model

Abstract Objective: The infusion of bone marrow cells into the damaged brain has been proposed as a new clinical practice for this disorder. Alternatively, hematopoietic growth factors may have a direct role on neural protection or have a mobilizing effect on bone marrow stem/progenitor cells to circulation for brain repair. Based on our previous findings, there are many similarities between megakaryocytes and neurons on functions and antigen expression such as neural marker MAP2, GFAP and Tau, 5-HT2A, 2B and 2C receptors (Stem Cells, 2014). Thrombopoietin (TPO) is a growth factor for megakaryocytic lineage. We postulate that TPO may play a role on neural protection or regeneration. The effect of TPO on nervous system has not been well investigated. Methods: To validate this hypothesis, we investigated the expression and role of TPO/TPO receptors in neural cells and a neonatal rat model of hypoxic-ischemic (HIE) brain damage. Results: To investigate the effect of TPO on in-vivo neural protection, a neonatal rat model of HIE brain damage was established. Brain injury was measured by the percentage weight reduction of the ipsilateral cerebral hemisphere as compared to the contralateral hemisphere. There was significantly less brain atrophy in TPO treated animals (12.0±1.2% and 11.5±1.0%) when compared with the saline control (21.0±1.6% and 24.4±2.2%) at 7 and 28 days post-operation (P<0.05, n=12). The percentage of NSE (Neuron-specific enolase) positive cells in the forelimb area of the cortex in the right hemisphere was significantly higher in the TPO group than that of the saline group (P<0.05, n=12). An improvement in sensory motor functions was also demonstrated after TPO treatment. TPO mRNA was also identified in human cerebral hemispheres, cerebellum, and mouse neural stem cell line C17.2 by RT-PCR methods. TPO protein was detected in human cerebrospinal fluids (n=10) by ELISA. Moreover, TPO receptor (c-mpl) mRNA was identified in human cerebral hemispheres and cerebellum, and C17.2 cells using RT-PCR. The expression of c-mpl protein was also confirmed on neurons in the human cerebral hemispheres, hippocampus, cerebellum, brainstem and spinal cord using immune-cytochemical staining. TPO also showed a stimulating effect on the in-vitro growth of C17.2 cells by the MTT assay. TPO activated the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway which was demonstrated by Western blot. The Akt activation by TPO was inhibited by the PI3-kinase inhibitor LY294002. Conclusions: Our study provided the evidences showing the expression of TPO and TPO receptor (c-mpl) in neural cells and this effect may be mediated by c-mpl and Akt signaling. More importantly, our observation further demonstrated the functional role of TPO on neural protection in a rat model. These findings point to the possibility of a new strategy for treating brain damage by hematopoietic growth factors. Disclosures Yang: National Natural Science Foundation of China: Other: National Natural Science Foundation of China(81270580).

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