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

摘要

Objective and importance: Hypoxic–ischemic brain injuries in childhood are associated withnpoor neurological outcome. Recently, experimental and clinical works show that nerve growthnfactor (NGF) reduces neurological deficits and promotes endothelial cells proliferation andnangiogenesis following hypoxic–ischemic brain injuries. After brain stroke, new neurons expressna protein, called doublecortin (DCX), which indicates a new marker for neurogenesis andnmigrating neuroblasts. This study investigates the effects of intraventricular NGF administrationnin two infants with severe hypoxic–ischemic brain damage and its role in both the cerebralnperfusion and neurogenesis.nClinical presentation: Two infants, aged 8 and 13 months, with hypoxic–ischemic brainndamage, secondary to prolonged cardiorespiratory arrest, were treated with intraventricular NGFnadministration. Before the therapy, both infants were comatose, aphasic and showed flaccidntetraparesis. After 1 month NGF treatment, their neurological conditions improved, electroencephalographyn(EEG) examinations showed increased alpha/theta ratio, and single photonnemission computed tomography (SPECT) works demonstrated a better cerebral perfusion. ThenDCX expression in the cerebrospinal fluid (CSF) increased concomitantly with increasing levelsnof NGF.nIntervention: The drug utilized was 2.5S NGF purified and lyophilized from male mousensubmaxillary glands. The NGF administration was started 4 months after ischemic brain injury.nNGF (0.1 mg) was administered via the external drainage catheter into the right cerebralnventricle once a day for 10 consecutive days.nConclusion: Our study shows that the intraventricular NGF administration improves the cerebralnperfusion and stimulates the pathway of neurogenesis differentiation with the activation of DCXnbiosynthesis. [Neurol Res 2008; 30: 223–228]