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Updated: Jul 4, 2026
The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Neuroprotective effects of vascular endothelial growth factor following hypoxic ischemic brain injury in neonatal
Yangzheng Feng1, Philip G Rhodes, Abhay J Bhatt
1Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Insights
Vascular Endothelial Growth Factor (VEGF) shows neuroprotective effects in newborn rats, reducing brain damage from hypoxic-ischemic (HI) injury. Optimal protection was observed with specific VEGF doses, potentially via the Akt/ERK signaling pathway.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Vascular Endothelial Growth Factor (VEGF) is known to protect adult brains from ischemic injury.
- Hypoxic-ischemic (HI) brain injury is a significant concern in newborns, leading to potential long-term neurological deficits.
- The neuroprotective role of VEGF in the developing brain, particularly following HI, remains to be fully elucidated.
Purpose of the Study:
- To investigate the potential neuroprotective effects of Vascular Endothelial Growth Factor (VEGF) in a neonatal rat model of hypoxic-ischemic (HI) brain injury.
- To determine the dose-dependent efficacy of VEGF administration in mitigating HI-induced brain damage.
- To explore the underlying molecular mechanisms, specifically the involvement of the Akt/ERK signaling pathway.
Main Methods:
- A hypoxic-ischemic (HI) brain injury model was established in 7-day-old rat pups by ligating the carotid artery and exposing them to hypoxia.
- Vascular Endothelial Growth Factor (VEGF) or vehicle was administered intracerebroventricularly after the HI insult.
- Brain damage was assessed by measuring hemispheric weight loss, gross morphology, and histological scoring at 22 days post-HI.
- VEGF levels, Akt, and ERK1/2 phosphorylation in the cortex were measured post-treatment.
Main Results:
- VEGF administration increased endogenous brain VEGF levels.
- VEGF treatment at 10 and 20 ng doses significantly reduced brain weight loss and gross brain injury compared to vehicle control (p < 0.05).
- Histological assessment confirmed reduced brain damage with 10 ng VEGF.
- VEGF administration led to increased phosphorylation of Akt and ERK1/2 in the cerebral cortex (p < 0.05).
Conclusions:
- Vascular Endothelial Growth Factor (VEGF) demonstrates significant neuroprotective effects against hypoxic-ischemic brain injury in neonatal rats.
- The neuroprotective efficacy of VEGF is dose-dependent, with optimal effects observed at 10 and 20 ng.
- Activation of the Akt/ERK signaling pathway is a likely mechanism mediating the neuroprotective actions of VEGF in the neonatal brain.
Abstract:
Vascular Endothelial Growth Factor (VEGF) protects the brain against ischemic injury in adult animals. We evaluated whether VEGF has neuroprotective effects against hypoxic-ischemic (HI) brain injury in newborn rats. Seven-day-old rat pups had the right carotid artery permanently ligated followed by 140 min of hypoxia (8% oxygen). VEGF (5, 10, 20, or 40 ng) or vehicle was administered intracerebroventricularly 5 min after reoxygenation following HI. Brain damage was evaluated by weight loss of the right hemisphere at 22 d after HI and by gross and microscopic morphology. Body weight, rectal temperature, and mortality were not significantly different in the VEGF and vehicle treated groups. VEGF treatment increased brain VEGF levels at 15 min after injection. VEGF (10 and 20 ng) significantly reduced brain weight loss (p < 0.05) and gross brain injury (p < 0.05); however, treatment with 5 or 40 ng did not. VEGF (10 ng) also decreased brain damage assessed by histologic scoring. VEGF increased phosphorylation of protein kinase B (Akt) and extracellular-signal regulated kinase 1/2 (ERK1/2) in the cortex (p < 0.05). These results suggest that VEGF has neuroprotective effects in the neonatal rat HI model that may be related to activation of the Akt/ERK signaling pathway.
