Papers by Alessia Antonelli
Neurotoxicology and Teratology, 2002
We previously reported that prenatal methylazoxymethanol (MAM) administered on days 11 and 12 of ... more We previously reported that prenatal methylazoxymethanol (MAM) administered on days 11 and 12 of rat pregnancy induces structural changes in the cytoarchitecture of the hippocampal-entorhinal axis. We also showed that young and middle-aged prenatally treated MAM animals displayed changes in brain neurotrophin levels [Neurosci. Lett. 309 (2001) 113; Physiol. Behav. 71 (2000) 57.]. To continue this line of investigation, the working hypothesis adopted was that prenatal MAM administration, by interfering with limbic neurogenesis, could impair learning and memory ability of aged animals in the water maze. It was found that injection of MAM during early rat brain development induced deficits in both the acquisition and retention phases of the Morris maze. These behavioral changes were associated with significant changes in brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), reduced choline acetyltransferase (ChAT) immunoreactivity in forebrain cholinergic neurons and loss of neuropeptide Y (NPY) immunodistribution in cells of the entorhinal cortex. This finding, as well as confirming previous studies showing that injection of prenatal MAM administration induces significant changes in hippocampal-entorhinal axis neurogenesis and marked behavioral deficits in adult life, provides additional experimental evidence supporting the hypothesis that loss of NGF and/or BDNF-receptive or producing cells can co-occur at the onset of neurodevelopmental disorders.
Neuroscience Letters, 2001
Rats prenatally exposed to the neurotoxins methylazoxymethanol (MAM) or 5-Bromo-2 H-deoxyuridine ... more Rats prenatally exposed to the neurotoxins methylazoxymethanol (MAM) or 5-Bromo-2 H-deoxyuridine (BrdU) are used as animal models of brain maldevelopment. We administered in rats MAM (20 mg/kg), or BrdU (100 mg/kg) or both at gestational day 11. Locomotion was not affected by any prenatal treatment whereas learning was delayed in the Morris maze in MAM animals. BrdU induced decreased NGF and BDNF levels in the hippocampus. In the parietal cortex prenatal BrdU administration induced NGF potentation associated with decreased BDNF. Animals treated with both MAM and BrdU showed also an increased immunopositivity for choline acetyltransferase (ChAT) and low af®nity neurotrophins' receptor (p75) in the septum and Meynert's nuclei. These ®ndings suggest that embryonic exposure to MAM and/or BrdU may be useful for studying mechanisms associated with neurodegenerative diseases affecting brain morphology and behavior.
Neuroscience Letters, 2001
We investigated the effect of hypergravitation on Nerve growth factor (NGF) and Brain-derived-neu... more We investigated the effect of hypergravitation on Nerve growth factor (NGF) and Brain-derived-neurotrophic factor (BDNF) expression in the visual cortex, geniculate nucleus (GN), and retina of adult male mice. The results showed that altered gravity causes an increase in NGF and BDNF in the visual cortex and GN which resulted to be associated with an up-regulation of cells immunoreactive to neuropeptide Y (NPY) in the visual cortex and GN. We also found a decrease in NGF, BDNF, and NPY in the mouse retina exposed to hypergravity. These ®ndings suggest that alteration in gravitational environment differentially affects local neurotrophic factors and NPY expression. The possible functional signi®cance of these observations is discussed.
Neuroscience Letters, 2002
Recent studies suggest that nerve growth factor (NGF), a neurotrophic factor known to play a cruc... more Recent studies suggest that nerve growth factor (NGF), a neurotrophic factor known to play a crucial role in neurite growth and differentiation, may also modulate vascular cell functions. In the present study, it was investigated whether NGF exhibits an angiogenic effect in a mouse model of hindlimb ischemia induced by femoral artery occlusion. Enzymelinked immunosorbent assay determination revealed an enhanced endogenous NGF production (378^100 and 54^26 pg/g tissue in 7 day ischemic and normoperfused adductor muscles, respectively; P , 0:05). Furthermore, exogenous NGF, administered subcutaneously for 7 days in ischemic hindlimb, induced a marked increase of arteriole length density (NGF ¼ 41^5 vs. Saline ¼ 22^4 mm/mm 3 ; P , 0:05). However, capillaries were not significantly increased (NGF ¼ 1035^182 vs. Saline ¼ 829^60 mm/mm 3 ; P. 0:05). In conclusion, the present study provides first evidence that NGF exerts angiogenic properties in vivo.
Neurological Research, 2005
Hypoxic-ischemic brain injuries in childhood are associated with poor neurological outcome. Recen... more 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, electroencephalography (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.
Leukemia Research, 2011
Brain damage related to intrathecal methotrexate in children with acute lymphoblastic leukemia (A... more Brain damage related to intrathecal methotrexate in children with acute lymphoblastic leukemia (ALL) is still unclear. Neuroinflammatory mechanisms and intracerebral production of specific biomarkers, play a key role in determining neuroprotective mechanisms after brain injury. To determine whether the CSF concentrations of neuron-specific enolase (NSE), neurotrophic factors and doublecortin (DCX) are influenced by repeated intrathecal methotrexate administrations, we prospectively collected CSF samples from 10 children with ALL and 10 controls. Our results showed an increased expression of the liquoral markers. This up-regulation could be interpreted as a neuroprotective response of the brain against the neuronal damages induced by MTX.
Journal of Trauma: Injury, Infection & Critical Care, 2008
Background: In the adult brain, migrating neuroblasts can replace damaged neurons after severe tr... more Background: In the adult brain, migrating neuroblasts can replace damaged neurons after severe traumatic brain injury (TBI). Little is known about which factors determine the magnitude and amplification of neurogenesis after TBI, but there are some evidences that the nerve growth factor (NGF) and the doublecortin (DCX) can influence neurogenesis and neuronal repair. Methods: This study investigates the NGF and DCX levels in the cerebrospinal fluid of 12 children with severe TBI and 12 matched controls, to determine the correlation between the expression of both these factors and the patients outcome. We collected cerebrospinal fluid samples 2 hours (Time T1) and 48 hours (Time T2) after brain injury. NGF levels were measured using a two-site immunoenzymatic assay, whereas the DCX expression by a Western blot analysis. Results: At time T1 and T2, children with the best outcomes had higher levels of NGF than children with poor outcomes. Evaluating the change of NGF levels from time T1 to time T2, we found that the NGF up-regulation in the early time after injury was significantly associated with good outcomes of patients. Concomitantly, the expression of DCX increased only in patients with NGF up-regulation from time T1 to time T2. In others patients and in controls the expression of DCX remained unchanged. Conclusion: Based on these results, we hypothesize that NGF and DCX contribute to the mechanisms of neuroprotection and neuronal connection reorganization after TBI, playing a key role in the outcome of these patients.
Journal of Neurotrauma, 2008
Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms ... more Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines. Interleukin-6 (IL-6) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor (NGF) biosynthesis. However, the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial. We have conducted a prospective observational clinical study to determine whether the concentration of IL-6 and NGF in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and neurologic outcome of patients. CSF samples were collected from 29 children at 2 h (time T1) and 48 h (time T2) after severe TBI, and from 31 matched controls. TBI severity was evaluated by Glasgow Coma Scale (GCS) and neurologic outcome by Glasgow Outcome Score (GOS). CSF concentrations of IL-6 and NGF were measured by immunoenzymatic assays. Early NGF concentrations (T1) correlated significantly with head injury severity, whereas no correlation was found between GCS and IL-6. Furthermore, IL-6 and NGF upregulation after injury was associated with better neurologic outcomes. Based on these findings, we posit that NGF expression is a useful marker of brain damage following severe TBI. Moreover, the early upregulation of both IL-6 and NGF, which correlates with a favorable neurologic outcome, may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult.
Journal of Neurotrauma, 2008
Glial-derived neurotrophic factor (GDNF) is one of several powerful survival factors for spinal m... more Glial-derived neurotrophic factor (GDNF) is one of several powerful survival factors for spinal motoneurons that play a key role in sprouting, synaptic plasticity, and reorganization after spinal cord damage. The aim of this study was to investigate the expression of GDNF in plasma of children with spina bifida (SB) and to determine its correlation with both the severity of spinal cord damage and the motor function of these patients. To measure the GDNF expression, we collected plasma samples from 152 children with SB and in 149 matched controls. Endogenous GDNF levels were quantified using a two-site immuno-enzymatic assay. The statistical analysis was performed using the Mann-Whitney two-tailed two-sample test. In children with SB the mean levels of GDNF (131.2 +/- 69.6 pg/mL) were significantly higher (p < 0.001) with respect to the mean levels of the control group (102.7 +/- 6.8 pg/mL). Moreover, in open SB, the GDNF levels (139.2 +/- 81.1 pg/mL) were significantly higher (p < 0.05) with respect to closed SB (117.2 +/- 41.3 pg/mL). In terms of the motor function of patients, we found that in children with poorer motor function, the GDNF levels (134.5 +/- 67.4 pg/mL) were higher, but not statistically significant (p < 0.1), than in patients with better motor outcome (122.3 +/- 72.2 pg/mL). Our study demonstrates GDNF over-expression in children with SB. This upregulation is significantly associated with the severity of spinal cord damage in SB patients and appears to correlate with poor motor function of children, representing an important biochemical marker of the severity of spine injury.
Journal of Neuroimmunology, 2003
In this study, we investigated whether hematopoietic stem cells (HSC) and progenitors present in ... more In this study, we investigated whether hematopoietic stem cells (HSC) and progenitors present in human cord blood can express nerve growth factor (NGF)-specific receptors, TrkA and p75. Our results showed a marked expression of TrkA and NGF in cord blood CD34(+) cells. A gradient of TrkA and NGF expression exists and is highest in cord blood CD34(+) cells, reduced in cord blood mononuclear cells (MNC) and minimal in mononuclear cells isolated from adult peripheral blood. Our findings suggest that NGF may play a role in the differentiation of hematopoietic progenitors and indicate a different requirement for NGF by immune cells, depending on their state of maturity.
Annali dell'Istituto …, 2003
Résumé/Abstract Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are member... more Résumé/Abstract Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are members of a family of structurally related secreted proteins, termed neurotrophins, which promote and regulate the survival of many kinds of neurons in the peripheral ...
Intensive Care Medicine, 2003
Objectives: We evaluated the neurotrophic factors [nerve growth factor (NGF), brain-derived neuro... more Objectives: We evaluated the neurotrophic factors [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), gliaderived neurotrophic factor (GDNF)] expression and their association with the severity and outcome of children with traumatic brain injury. Design: Prospective observational clinical study. Setting: Pediatric intensive care unit. Patients: Fourteen children with severe head injury; 12 controls with obstructive hydrocephalus. Measurement: Cerebrospinal fluid (CSF) and plasma samples were collected 2 h (T1) and 24 h (T2) after head injury. Neurotrophic factor levels were measured using an immunoenzymatic assay. Main results: In patients, neurotrophic factor mean levels were significantly different in both CSF and plasma, showing high levels of BDNF compared to NGF and GDNF. Considering T1 and T2 expression, in the CSF the level of NGF increased from 3.5±0.4 pg/ml to 48.2±11.7 pg/ml (p<0.001); BDNF decreased from 4854.0± 1303.7 pg/ml to 593.0±114.8 pg/ml (p<0.001), while GDNF did not undergo significant variations. In plasma, no significant changes were observed. Regarding severity and outcome, BDNF levels showed a sharp peak after head injury, but the only significant association was between NGF expression in the CSF and a good outcome versus a poor outcome (p=0.007). Conclusions: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after traumatic head injury. BDNF represents an early marker of brain injury, while NGF expression in the CSF was indicative of a good outcome and the role of this neurotrophin in the treatment of children with severe head injury may be hypothesized.
European Journal of Paediatric Neurology, 2008
Background-Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory m... more Background-Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory mechanisms, mainly dependent on the intracerebral production of cytokines. In particular, interleukin 1β (IL-1β) is associated with neuronal damage, while interleukin 6 (IL-6) exerts a neuroprotective role due to its ability to modulate neurotrophins biosynthesis. However, the relationship between these cytokines and neurotrophins with the severity and outcome of TBI remains still controversial. Aims-To determine whether the concentration of IL-1β and IL-6 and neurotrophins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF)) in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and its neurologic outcome. Methods-Prospective observational clinical study in a university hospital. CSF samples were collected from 27 children at 2h (Time T1) and 48h (Time T2) after severe TBI, and from 21 matched controls. Severity of TBI was evaluated by GCS and neurologic outcome by GOS. CSF concentrations of cytokines and neurotrophins were measured by immunoenzymatic assays. Results-Early NGF and IL-1β concentrations (T1) correlated significantly with the severity of head injury, whereas no correlation was found for IL-6, BDNF, and GDNF. Furthermore, higher NGF and IL-6 and lower IL-1β expression at T2 were associated with better neurologic outcomes. No significant association was found between BDNF or GDNF expression and neurologic outcome. Conclusions-NGF concentration in CSF is a useful marker of brain damage following severe TBI and its up-regulation, in the first 48 h after head injury together with lower IL-1β expression, correlates with a favorable neurologic outcome. Clinical and prognostic information may also be obtained from IL-6 expression.
European Journal of Cancer Care, 2010
Propofol/alfentanil and propofol/ketamine procedural sedation in children with acute lymphoblasti... more Propofol/alfentanil and propofol/ketamine procedural sedation in children with acute lymphoblastic leukaemia: safety, efficacy and their correlation with pain neuromediator expression Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukaemia (ALL). We investigated the safety and efficacy of two different protocols for analgo-sedation in 20 children with ALL undergoing lumbar puncture. We have conducted a prospective, cross-over study. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. We also evaluated the levels of nerve growth factor, substance P and enkephalins in the cerebrospinal fluid of these patients. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significant differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Pain neuromediator levels did not show any statistical difference between the two groups. This study shows that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears to be safer due to the lower incidence of side effects.
Developmental Brain Research, 2000
A number of studies have shown that mothering style in rodents can produce neuroendocrine, neuroc... more A number of studies have shown that mothering style in rodents can produce neuroendocrine, neurochemical and behavioural changes in the adult, although the basic mechanisms initiating this cascade of events still need to be investigated. Long term changes in neuronal function might be due to alterations in the expression of neurotrophins which have been shown to promote neuronal survival, differentiation and function during development, such as Nerve Growth Factor (NGF). NGF is essential for proper development of sympathetic and neural crest-derived sensory neurons of the peripheral nervous system as well as of central cholinergic neurons. In previous studies, using a maternal separation paradigm, we have shown that NGF expression is increased in the dentate gyrus and the hilus of the hippocampus as a result of brief (45 min) maternal separations. In the present study neonatal rats were separated for longer periods of time (up to 3 h) and at different ages during development (9 and 16 days postnatally). Results indicate that the effects of maternal separation on NGF expression are stronger with longer separations and are not restricted to the hippocampal region but can be seen also in other brain areas. Overall these results indicate that external factors, such as the presence / absence of the mother, can modify neurotrophic factor's availability in the brain, thus indicating NGF as a potential player in environmentally-mediated brain plasticity during development.
Child's Nervous System, 2007
Pain is the most common discomfort experienced by children undergoing major operations. It is mos... more Pain is the most common discomfort experienced by children undergoing major operations. It is most often not adequately treated because of inexperience and unfounded fears related to the use of opioid drugs. In adults, patient-controlled analgesia (PCA) is widely administered, while in children, its use with opioid drugs is still under evaluation for safety and efficacy. The objective of the study is to evaluate the safety and efficacy of an opioid drug (fentanil) administered by PCA associated with a sedative-adjuvant drug (midazolam) administered by continuous infusion in children having undergone major neurosurgical procedures. Sixteen children with moderate to severe postoperative pain were treated with fentanil by PCA (booster doses of 1 microg/kg) plus continuous infusion of midazolam (2 microg/kg per min) by an intravenous route. To evaluate safety and efficacy of this analgesic protocol, different subjective and objective parameters were monitored at 4-h intervals. In addition, patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; satisfaction was assessed by a questionnaire at the end of the treatment. All children experienced a good degree of analgesia and did not require any other analgesic drug during the treatment. Both subjective and objective parameters improved after starting pain-relieving treatment, and no major side effects occurred. The analysis of the answers of the questionnaire administered to the children showed a high grade of satisfaction. PCA with fentanil plus continuous infusion of midazolam is a safe and efficacious method for analgesia in children with moderate to severe postoperative neurosurgical pain. The association of midazolam to fentanil also contributes to control anxiety and stress in this subset of patients and does not show any important side effects.
Child's Nervous System, 2004
Neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF] and gli... more Neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) are growth factors implicated in the growth and differentiation of brain nerve cells. An involvement of these factors in the biology and progression of some specific tumours has been suggested. In accordance with the role of neurotrophic factors in tumour behaviour the aim of the present study was to investigate their expression in two childhood brain neoplasms, namely low-grade astrocytomas and ependymomas. We investigated the NGF, BDNF, GDNF and NGF receptors (TrkA and p75) expression in the tumour tissues, cerebrospinal fluid (CSF) and plasma of ten children affected by low-grade astrocytomas and ependymomas. Control tissue samples (together with CSF and plasma samples) were obtained from patients who underwent surgery for cerebral vascular or epileptogenic lesions. The expression of NGF decreases both in tumour samples and in the CSF of affected children compared with controls. BDNF instead increases in CSF, while the expression of GDNF remains unchanged both in tissues and in CSF. No differences were found in neurotrophic factor plasma levels in patients or in controls. Gene expression of NGF and its high-affinity receptor (TrkA) are reduced in tumour tissues, whereas the number of cells immunopositive to the low-affinity NGF receptor (p75) is increased. Reduced expression of NGF and TrkA has been shown in low-grade astrocytomas and ependymomas. These findings may be related to the role of this neurotrophin in cell differentiation and apoptosis. The different expression of NGF, BDNF, and GDNF in low-grade astrocytomas and ependymomas suggests that a different degree of redundancy exists among members of the neurotrophic factor family and that their expression may be correlated with the biology and the behaviour of these tumours.
Child's Nervous System, 2004
Based on the known inflammatory role of interleukins (IL), we evaluated IL-1beta and IL-6 express... more Based on the known inflammatory role of interleukins (IL), we evaluated IL-1beta and IL-6 expressions and their association with the severity of traumatic brain injury (TBI; Glasgow Coma Scale [GCS]) and the outcome (Glasgow Outcome Score [GOS]) recorded in a paediatric population. The design was a perspective observational clinical study carried out in the paediatric intensive care unit of the University Hospital. We measured the IL-1beta and IL-6 levels in 14 children with severe TBI (patients) and in 12 children with obstructive hydrocephalus (control group). Cerebrospinal fluid (CSF) and plasma samples were collected 2 h (T1) and 24 h (T2) after TBI. Interleukins were assayed using the immunoenzymatic method. The IL-1beta mean level was significantly lower than the IL-6 mean level both in the CSF and plasma of TBI children. In the CSF, the IL-1beta level increased from 55.71+/-72.79 pg/ml at T1 to 106.10+/-142.12 pg/ml at T2 and the IL-6 level increased from 405.43+/-280.28 pg/ml at T1 to 631.57+/-385.35 pg/ml at T2; a similar trend was observed in plasma. We found a statistically significant correlation between the increase in CSF and plasma interleukin levels between T1 and T2 and head injury severity (GCS&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=5) as well as poor outcome (GOS&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=3). The increases in IL-1beta and IL-6 expression were correlated with head injury severity and were indicative of poor clinical outcome, reflecting an endogenous neuroinflammatory response after TBI.
Child's Nervous System, 2011
The effects on neural repair of intraparenchymal nerve growth factor (NGF) administration were ev... more The effects on neural repair of intraparenchymal nerve growth factor (NGF) administration were evaluated in neonate Wistar rats with experimentally induced focal microgyria. A freezing focal polymicrogyric lesion was induced on the frontal cortex in 35 newborn Wistar rats on postnatal day 1. NGF was administered in 15 cases, with 20 pups as controls. Animals were sacrificed at 72 h and 7 days after NGF administration. Real-time PCR was used for the quantification of the expression of TrkA, p75, and doublecortin (DCX) at the level of the cortical lesion in seven different groups of animals: control 72 h (n = 5), control 7 days (n = 5), microgyria 72 h (n = 5), microgyria 7 days (n = 5), microgyria + NGF 72 h (n = 5), microgyria + NGF 7 days (n = 5), and control + NGF (n = 5). A significant increase in TrkA expression was found in the microgyria + NGF 7 days group compared to the others. TrkA upregulation was already visible 72 h after NGF administration. Unlike TrkA, p75 expression increased in animals subjected to the experimental focal microgyria and decreased markedly after NGF administration. DCX expression in injured animals was observed to increase strongly 7 days after NGF administration compared with other groups. NGF administration interferes with neural repair mechanisms at the polymicrogyric lesion site by means of TrkA and DCX upregulation which possibly counteracts the process of apoptosis caused by the brain injury.
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Papers by Alessia Antonelli