- 作者: Pei Chun Lai; Yen Ta Huang; Chia Chen Wu; Ching Jung Lai; Pen Jung Wang; Ted H Chiu
- 作者服務機構: Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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.
- 中文關鍵字: --
- 英文關鍵字: β-lactam antibiotics, ceftriaxone, hypoxic-ischemic injury, neonatal rat, GLT1, EAAT2