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Intraventricular nerve growth factor infusion improves cerebral blood flow and stimulates doublecortin expression in
Antonio Chiaretti1, Alessia Antonelli, Orazio Genovese
1Pediatric Intensive Care Unit, Catholic University Medical School, Rome, Italy. achiaretti@yahoo.it
Insights
Nerve growth factor (NGF) treatment improved cerebral perfusion and stimulated neurogenesis in infants with severe hypoxic-ischemic brain damage. This suggests NGF is a potential therapeutic agent for pediatric brain injury.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pediatric Neurology
Background:
- Hypoxic-ischemic brain injuries in children often lead to poor neurological outcomes.
- Nerve growth factor (NGF) has shown potential in experimental and clinical studies to reduce neurological deficits and promote angiogenesis after brain injury.
- Doublecortin (DCX) is a protein marker for neurogenesis and migrating neuroblasts following brain stroke.
Observation:
- Two infants (8 and 13 months) with severe hypoxic-ischemic brain damage received intraventricular NGF.
- Before treatment, infants were comatose, aphasic, and exhibited flaccid tetraparesis.
- NGF administration occurred 4 months post-injury, with 0.1 mg daily for 10 days via intraventricular catheter.
Findings:
- Following 1 month of NGF treatment, neurological conditions improved, with increased alpha/theta ratio on EEG.
- Single photon emission computed tomography (SPECT) revealed enhanced cerebral perfusion.
- Cerebrospinal fluid (CSF) analysis showed increased DCX expression, correlating with NGF levels.
Implications:
- Intraventricular NGF administration appears to improve cerebral perfusion in infants with severe brain damage.
- NGF treatment stimulates neurogenesis pathways, evidenced by increased DCX biosynthesis.
- This study highlights NGF's potential as a therapeutic agent for pediatric hypoxic-ischemic brain injury.
Objective And Importance:
Hypoxic-ischemic brain injuries in childhood are associated with poor neurological outcome. Recently, experimental and clinical works show that nerve growth factor (NGF) reduces neurological deficits and promotes endothelial cells proliferation and angiogenesis following hypoxic-ischemic brain injuries. After brain stroke, new neurons express a protein, called doublecortin (DCX), which indicates a new marker for neurogenesis and migrating neuroblasts. This study investigates the effects of intraventricular NGF administration in two infants with severe hypoxic-ischemic brain damage and its role in both the cerebral perfusion and neurogenesis.
Clinical Presentation:
Two infants, aged 8 and 13 months, with hypoxic-ischemic brain damage, secondary to prolonged cardiorespiratory arrest, were treated with intraventricular NGF administration. Before the therapy, both infants were comatose, aphasic and showed flaccid tetraparesis. After 1 month NGF treatment, their neurological conditions improved, electro-encephalography (EEG) examinations showed increased alpha/theta ratio, and single photon emission computed tomography (SPECT) works demonstrated a better cerebral perfusion. The DCX expression in the cerebrospinal fluid (CSF) increased concomitantly with increasing levels of NGF.
Intervention:
The drug utilized was 2.5S NGF purified and lyophilized from male mouse submaxillary glands. The NGF administration was started 4 months after ischemic brain injury. NGF (0.1 mg) was administered via the external drainage catheter into the right cerebral ventricle once a day for 10 consecutive days.
Conclusion:
Our study shows that the intraventricular NGF administration improves the cerebral perfusion and stimulates the pathway of neurogenesis differentiation with the activation of DCX biosynthesis.
