Related Experiment Video
Updated: May 29, 2026
The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats
Pei Chun Lai1, Yen Ta Huang, Chia Chen Wu
1Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
Insights
Ceftriaxone pre-treatment reduces brain injury in neonatal rats with hypoxic-ischemic encephalopathy (HIE). This neuroprotective effect is linked to enhanced glutamate transporter GLT1 expression, potentially preventing neuronal damage.
Area of Science:
- Neuroscience
- Neonatal Research
- Pharmacology
Background:
- Perinatal brain injury is a primary cause of neurological disability in newborns.
- Glutamate excitotoxicity significantly contributes to hypoxic-ischemic encephalopathy (HIE).
- Immature astrocytes in HIE may fail to clear excessive glutamate, leading to neuronal damage.
Purpose of the Study:
- To investigate the neuroprotective potential of ceftriaxone in a neonatal rat model of HIE.
- To assess the effect of ceftriaxone on glutamate transporter GLT1 expression and neuronal damage.
Main Methods:
- A neonatal rat model of HIE was established using carotid artery ligation and hypoxia.
- Rats received ceftriaxone at varying doses prior to HIE induction.
- Neurobehavioral tests, histological analyses (Nissl, TUNEL), and Western blot for GLT1 were performed.
Main Results:
- Ceftriaxone pre-treatment significantly decreased brain injury scores and apoptosis in the hippocampus.
- Myelination was restored in the external capsule, and learning/memory deficits were improved.
- Ceftriaxone administration increased GLT1 expression in cortical neurons.
Conclusions:
- Ceftriaxone demonstrates significant neuroprotective effects against HIE-induced brain injury in neonatal rats.
- Enhanced GLT1 expression is a potential mechanism underlying ceftriaxone's neuroprotection.
- Pre-treatment with ceftriaxone may be a viable strategy to mitigate brain injury in at-risk infants.
Background:
Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE.
Methods:
We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7) rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry.
Results:
Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats.
Conclusion:
These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.
