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Hypoxic-ischemic encephalopathy (HIE) animal model

Hypoxic-ischemic encephalopathy (HIE) animal model

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Hypoxic-ischemic brain injury
Psychiatric & neurological disease models

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Model Introduction

Model Introduction

Platform Service Advantages

Platform Service Advantages

Experimental results

Experimental results

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Hypoxic-ischemic brain injury

Introduction to the HIE Animal Model

Hypoxic‑Ischemic Encephalopathy (HIE) in neonatal rats is an animal model used to study perinatal brain injury. This model is typically established by inducing hypoxia and ischemia in neonatal rats, thereby mimicking the brain damage that occurs in fetuses or newborns during the perinatal period due to reduced or interrupted cerebral blood flow caused by various etiologies.

Advantages of Aniphe BioLab’s HIE Animal Model Platform Services

Comprehensive model coverage

Classic and mature

The classic HIE modeling method was employed, yielding a stable and highly reproducible model.

Standardization of the modeling process

Standard Procedure

Strictly control key steps in the modeling process to ensure experimental consistency and data reliability.

Multidimensional Evaluation System

Clearly defined phenotype

The extent of brain injury can be directly assessed through histopathological examination and tissue staining.

Modeling cycle

1–4 weeks

1  Laboratory animals

SD rat

1  Positive drug

Classic positive treatments include therapeutic hypothermia, NMDA receptor antagonists, antioxidants, and neurometabolic enhancers.

1  Application areas

Neuroprotective drug development, research on the mechanisms of hypoxic-ischemic encephalopathy (HIE), studies on brain injury repair, evaluation of stem cell and exosome therapies, and preclinical efficacy assessment.

Experimental results

Methods for Establishing HIE Animal Models

Seven-day-old Sprague-Dawley neonatal rats were anesthetized with isoflurane, and the left common carotid artery was ligated and transected. Two hours postoperatively, they were subjected to 90 minutes of 8% hypoxia, after which they were returned to their cages for recovery.

H&E staining

HE staining revealed that, compared with the normal control group, the rat brain tissue in the hypoxic‑ischemic brain injury model exhibited extensive areas of pale staining, disorganized neuronal arrangement, shrunken cell bodies, and pyknotic nuclei, indicating significant ischemic injury and neuronal death, thereby confirming the successful establishment of the model.

 

Therapeutic outcomes of recombinant human erythropoietin (rhEPO)

01 Weight Measurement Results

At the early postnatal period (P1–P10), there were no significant differences in body weight among the groups. Following model induction, as postnatal age increased, the HI‑model group exhibited a significantly slower rate of weight gain compared with the Sham group (P<0.05), suggesting that hypoxic‑ischemic brain injury impairs growth and development in young rats. In contrast, rhEPO treatment markedly restored the rate of weight gain in HI‑treated rats, effectively alleviating the growth retardation induced by hypoxic‑ischemic injury.

02 Behavioral Assessment Results

Morris water maze results showed that, compared with the Sham group, HI‑model rats exhibited prolonged escape latency in the spatial navigation task, reduced number of platform crossings during the probe trial, and shortened time spent in the target quadrant, indicating persistent impairments in learning and spatial memory following hypoxic‑ischemic brain injury. Following rhEPO treatment, the rats demonstrated improved learning acquisition, with a significant increase in the number of platform crossings and an extended duration of time spent in the target quadrant, thereby confirming that rhEPO can effectively ameliorate long‑term cognitive deficits induced by HI.

03 Histological Analysis of Brain Tissue

Hematoxylin–eosin staining of brain tissue revealed that, in the Sham group, hippocampal and cortical neurons exhibited intact morphology and orderly arrangement; in the HI model group, numerous neurons were markedly pyknotic and lost, with evident tissue damage. RhEPO intervention significantly ameliorated neuronal necrosis and histopathological injury induced by hypoxia–ischemia, thereby exerting a neuroprotective effect.

04 Immunofluorescence Staining Results

TUNEL staining results demonstrated that hypoxic–ischemic injury significantly increases the level of neuronal apoptosis in the cortex and hippocampus of neonatal rats; rhEPO treatment markedly reduces the number of TUNEL‑positive apoptotic cells, thereby exerting neuroprotective effects against brain injury by inhibiting neuronal apoptosis.

05 Immunohistochemistry and Western blot assay results

Immunohistochemical analysis revealed that, compared with the Sham group, the HI‑model rats exhibited significantly elevated expression of the inflammatory protein COX‑2 and the apoptotic protein Cleaved‑Caspase‑3 in brain tissue; rhEPO treatment markedly attenuated the positive staining for both markers. Western blot quantification indicated that HI injury suppressed Akt protein phosphorylation, whereas rhEPO upregulated p‑Akt levels. In summary, rhEPO mitigates neonatal brain injury by activating the PI3K/Akt survival pathway, thereby inhibiting hypoxia‑ischemia‑induced neuroinflammation and neuronal apoptosis.

References: Recombinant human erythropoietin protects against immature brain damage induced by hypoxic/ischemia insult