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Neuroprotective role of nerve growth factor in hypoxic-ischemic brain injury.

Fantacci C, Capozzi D, Ferrara P, Chiaretti A - Brain Sci (2013)

Bottom Line: Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement.Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system.Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Neuroscience, Catholic University of Rome, Largo A. Gemelli 8, Rome 00168, Italy. claudiafantacci@yahoo.it.

ABSTRACT
Hypoxic-ischemic brain injuries (HIBI) in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG) and cerebral perfusion at single-photon emission computed tomography (SPECT). The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

No MeSH data available.


Related in: MedlinePlus

Serial electroencephalogram (EEG) examinations performed before and after the treatment with intraventricular Nerve Growth Factor (NGF) administration showed a constant and progressive reduction in slow-wave activity expressed as an increased alpha/theta ratio in both patients (A) patient 1; (B) patient 2.
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brainsci-03-01013-f002: Serial electroencephalogram (EEG) examinations performed before and after the treatment with intraventricular Nerve Growth Factor (NGF) administration showed a constant and progressive reduction in slow-wave activity expressed as an increased alpha/theta ratio in both patients (A) patient 1; (B) patient 2.

Mentions: Concerning eventual therapeutic use of neurotrophins in children who suffered from HIBI, our experience provides encouraging results of intraventricular NGF infusion in two infants with prolonged cardio-respiratory arrest, for whom no new therapeutic approaches were proposed other than the conventional treatment. Before NGF administration, severe comatose state, flaccid tetraparesis, and complete aphasia were apparently stabilized in both patients. After the NGF therapy, both infants showed a significant improvement in motor and cognitive functions, with good recovery of their level of awareness, finalistic movements, and amelioration of their communicative skills. The improvement in the state of consciousness and in the communicative functions is congruent with the hypothesis of NGF-induced enhancement of cholinergic brain functions [18]. In these patients, serial EEG recordings showed an important reduction of slow-wave activity after the NGF treatment, and a simultaneous increase in higher frequencies, approximating a more normal EEG pattern (Figure 2). Also SPECT imaging showed a significant improvement of cerebral perfusion related to the concomitant increase of NGF levels in the CSF (Figure 3) [19]. Intraventricular NGF infusion was followed by an improvement of regional cerebral perfusion and selective neurogenesis was demonstrated by the regional 99mTc-ECD uptake increase, reflecting a new cerebral tissue viability and cholinergic functions, as previously reported in literature [20,21].


Neuroprotective role of nerve growth factor in hypoxic-ischemic brain injury.

Fantacci C, Capozzi D, Ferrara P, Chiaretti A - Brain Sci (2013)

Serial electroencephalogram (EEG) examinations performed before and after the treatment with intraventricular Nerve Growth Factor (NGF) administration showed a constant and progressive reduction in slow-wave activity expressed as an increased alpha/theta ratio in both patients (A) patient 1; (B) patient 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061878&req=5

brainsci-03-01013-f002: Serial electroencephalogram (EEG) examinations performed before and after the treatment with intraventricular Nerve Growth Factor (NGF) administration showed a constant and progressive reduction in slow-wave activity expressed as an increased alpha/theta ratio in both patients (A) patient 1; (B) patient 2.
Mentions: Concerning eventual therapeutic use of neurotrophins in children who suffered from HIBI, our experience provides encouraging results of intraventricular NGF infusion in two infants with prolonged cardio-respiratory arrest, for whom no new therapeutic approaches were proposed other than the conventional treatment. Before NGF administration, severe comatose state, flaccid tetraparesis, and complete aphasia were apparently stabilized in both patients. After the NGF therapy, both infants showed a significant improvement in motor and cognitive functions, with good recovery of their level of awareness, finalistic movements, and amelioration of their communicative skills. The improvement in the state of consciousness and in the communicative functions is congruent with the hypothesis of NGF-induced enhancement of cholinergic brain functions [18]. In these patients, serial EEG recordings showed an important reduction of slow-wave activity after the NGF treatment, and a simultaneous increase in higher frequencies, approximating a more normal EEG pattern (Figure 2). Also SPECT imaging showed a significant improvement of cerebral perfusion related to the concomitant increase of NGF levels in the CSF (Figure 3) [19]. Intraventricular NGF infusion was followed by an improvement of regional cerebral perfusion and selective neurogenesis was demonstrated by the regional 99mTc-ECD uptake increase, reflecting a new cerebral tissue viability and cholinergic functions, as previously reported in literature [20,21].

Bottom Line: Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement.Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system.Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Neuroscience, Catholic University of Rome, Largo A. Gemelli 8, Rome 00168, Italy. claudiafantacci@yahoo.it.

ABSTRACT
Hypoxic-ischemic brain injuries (HIBI) in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG) and cerebral perfusion at single-photon emission computed tomography (SPECT). The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

No MeSH data available.


Related in: MedlinePlus