Intraventricular nerve growth factor infusion improves cerebral blood flow and stimulates doublecortin expression in two infants with hypoxic-ischemic brain injury.
OBJECTIVE
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Chiaretti
Antonio
A
Pediatric Intensive Care Unit, Catholic University Medical School, Rome, Italy. achiaretti@yahoo.it
Antonelli
Alessia
A
Genovese
Orazio
O
Fernandez
Eduardo
E
Giuda
DanielaDi
D
Mariotti
Paolo
P
Riccardi
Riccardo
R
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004569:Electroencephalography; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007223:Infant; D007276:Injections, Intraventricular / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000134:cerebrospinal fluid*; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000378:metabolism; D009460:Neurologic Examination; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D013363:Submandibular Gland / Q000737:chemistry; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D020932:Nerve Growth Factor