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Ying-Chao Chang

Publications and source records attributed to Ying-Chao Chang.

13 recordsLinked to original sources
PubMed2006

Early-life fluoxetine exposure reduced functional deficits after hypoxic-ischemia brain injury in rat pups.

Neuroplasticity after perinatal programming may allow for neuroprotection against hypoxic-ischemia (HI) at birth. The cAMP response element-binding protein (CREB) is a key mediator of stimulus-induced nuclear responses that underlie survival, memory and plasticity of nervous system. Chronic treatment of fluoxetine, a selective serotonin reuptake inhibitor, can upregulate CREB activation in the hippocampus. We examined whether fluoxetine administration before HI may protect against neonatal HI brain injury through CREB-mediated mechanisms. We found that low-dose fluoxetine pretreatment in a neonatal HI brain injury model significantly reduced functional deficits at adulthood. The neuroprotective mechanisms were associated with increased CREB phosphorylation and increased brain-derived neurotrophic factor and synapsin I mRNA expression in the hippocampus. Neurogenesis also increased because of greater precursor cell survival in the hippocampal dentate gyrus. These findings suggest that functional deficits after HI in the developing brain can be reduced by agents that enhance neural plasticity and neurogenesis through CREB activation.

Aging↗
PubMed2006

Perinatal brain injury and regulation of transcription.

PURPOSE OF REVIEW: Perinatal hypoxic-ischemic brain injury is a major cause of mortality and morbidity in infants. The understanding of transcription factor activation leading to prosurvival gene expression is important as it pertains to the development of new therapy. Here, we highlight the regulation of transcription factors that potentially could promote neuro-survival in the immature brain. RECENT FINDINGS: cAMP response element binding protein (CREB), nuclear factor-kappaB (NF-kappaB) and hypoxia-inducible factor 1 (HIF-1) are developmentally regulated in the neural system, and are necessary for the induction of preconditioning against hypoxic-ischemia. CREB and NF-kappaB are also involved in the regulation of synaptic plasticity, and learning and memory. CREB phosphorylation is sufficient and necessary for survival in adult and immature neurons, and NF-kappaB activation in neurons could promote survival, whereas activation in glial cells enhances neuronal death. Although HIF-1 is necessary for hypoxic preconditioning, paradoxically, in the absence of preconditioning, this factor promotes ischemia-induced neuronal death. Erythropoietin, one of the HIF-1 targeted genes, is potently neuroprotective and may be beneficial in treating newborns with hypoxic-ischemic brain damage. SUMMARY: Drugs that activate the specific signaling leading to the transcriptional activation of prosurvival genes may provide therapy for the treatment of perinatal hypoxic-ischemic brain injury. Investigation of the transcriptional mechanisms of neuro-survival is likely to reveal other novel transcription factors whose activation by small molecules or drugs will complement current medication in activating the salutary gene program.

Age Factors↗
PubMed2005

Neonatal neurological disorders involving the brainstem: neurosonographic approaches through the squamous suture and the foramen magnum.

Brainstem damage which often indicates a critical condition is usually underestimated by trans-anterior-fontanel neurosonography (NS) owing to the far-field limitations. Instead, NS alternately scanning through the squamous suture of the temporal bones and the foramen magnum could provide a better visualization of the brainstem structures. The NS characteristics of brainstem lesions caused by various neonatal neurological disorders, such as hypoxic-ischemic encephalopathy (HIE), metabolic encephalopathy, birth trauma and bacterial meningoencephalitis, can be depicted at the acute stage. An echogenic change in the midbrain was found in patients with HIE or metabolic encephalopathy. In addition to the echogenic change, bilateral transtentorial temporal lobe herniation distorting the contour of the midbrain was observed in a patient with group B streptococcus meningoencephalitis, whereas echogenic changes at the level of the pons and/or the medulla oblongata, mainly localized in the dorsal part, could be observed in newborns with severe HIE, maple syrup urine disease or birth trauma. In this pictorial assay, we demonstrate the feasibility of NS imaging in evaluating the entire brainstem structure of critically ill neonates in the near field and illustrate the characteristic features of brainstem involvement in various neonatal neurological disorders along with computed tomography or magnetic resonance imaging correlation.

Birth Injuries↗
PubMed2005

Repetitive febrile seizures in rat pups cause long-lasting deficits in synaptic plasticity and NR2A tyrosine phosphorylation.

Adult rats with early-life frequently repetitive febrile seizures (FRFS), but not single febrile seizure (SFS), exhibited impaired performance in inhibitory avoidance tasks but without significant hippocampal neuronal loss. The mechanisms of long-term memory impairment in the hippocampus of adult rats with early-life FRFS remain unknown. Using a heated-air febrile seizures (FS) paradigm, male rat pups were subjected to single or nine episodes of brief FS at days 10 to 12 postpartum. We found that early-life FRFS led to long-term bidirectional modulation in hippocampal synaptic plasticity, i.e., impaired long-term potentiation and facilitated long-term depression. Three hours after inhibitory avoidance training, phosphorylation of hippocampal extracellular signal-regulated kinase (ERK) 1/2 was significantly less in the FRFS group than in controls. Furthermore, there was a selective alteration in NMDA receptor-mediated ERK1/2 phosphorylation in the hippocampus of the FRFS group. Although the expression levels of NMDA receptor subunits and interaction of NMDA receptor and postsynaptic density 95 did not alter quantitatively, there was a specific alteration in NR2A, but not NR2B, subunit tyrosine phosphorylation after NMDA stimulation in the FRFS group. These data offer a potential molecular explanation for the hippocampus-dependent memory deficits observed in the rats with early-life FRFS.

Animals↗
PubMed2004

cAMP response element-binding protein activation in ligation preconditioning in neonatal brain.

Perinatal hypoxic-ischemic (HI) brain injury is a major cause of permanent neurological dysfunction in children. An approach to study the treatment of neonatal HI encephalopathy that allows for neuroprotection is to investigate the states of tolerance to HI. Twenty-four-hour carotid-artery ligation preconditioning established by delaying the onset of hypoxia for 24 hours after permanent unilateral carotid ligation rats markedly diminished the cerebral injury, however, the signaling mechanisms of this carotid-artery ligation preconditioning in neonatal rats remain unknown. Ligation of the carotid artery 24 hours before hypoxia provided complete neuroprotection and produced improved performance on the Morris water maze compared with ligation performed 1 hour before hypoxia. Carotid artery ligation 6 hours before hypoxia produced intermediate benefit. The 24-hour carotid-artery ligation preconditioning was associated with a robust and sustained activation of a transcription factor, the cAMP response element-binding protein (CREB), on its phosphorylation site on Ser133. Intracerebroventricular infusions of antisense CREB oligodeoxynucleotides significantly reduced the 24-hour carotid-artery ligation-induced neuroprotection effects by decreasing CREB expressions. Pharmacological activation of the cAMP-CREB signaling with rolipram 24 hours before hypoxia protected rat pups at behavioral and pathological levels by sustained increased CREB phosphorylation. This study suggests that 24-hour carotid-artery ligation preconditioning provides important mechanisms for potential pharmacological preconditioning against neonatal HI brain injury.

Analysis of Variance↗
PubMed2004

Seizures complicating infantile and childhood bacterial meningitis.

In this study, 116 patients, at least 1 month of age but younger than 5 years, were identified with culture-proven bacterial meningitis. A comparison was made between the clinical data of the patients with and without seizures during hospitalization. Seizures during acute bacterial meningitis accounted for 47% (55/116) of the episodes. Time interval between the onset of bacterial meningitis and that of seizures was 1 to 20 days (mean, 4 days). Twelve of these 55 patients had one or more afebrile seizures after completing the treatment. At follow-up of at least 1 year after completing treatment, 26 patients had good outcomes, whereas the other 29 patients had poor outcomes. A strong correlation between the findings of abnormalities through neuroimaging and the occurrence of seizures during hospitalization was observed. The long-term outcomes of patients with infantile and childhood bacterial meningitis, who had seizures during the acute phase of bacterial meningitis, were worse than the outcomes of those who did not have such seizures. No child developed late seizures unless there were acute seizures. Factors associated with seizures during acute bacterial meningitis include disturbed consciousness on admission, abnormal neuroimaging findings, and low glucose and high concentration of total proteins in cerebrospinal fluid.

Chi-Square Distribution↗
PubMed2004

Bacterial meningitis in infants: the epidemiology, clinical features, and prognostic factors.

This 16-year (1986-2001) retrospective study enrolled 80 infantile patients (aged, 30-365 days old) with culture-proven bacterial meningitis. The most prevalent pathogens were Salmonellaspecies, Streptococcus (S.) agalactiae, Escherichia (E.) coli, and Haemophilus (H.) influenzae, accounting for about 59% of the episodes. Meningitis caused by Salmonella species, E. coli and H. influenzae occurs more often in the older infants, while that caused by S. agalactiae occurs more often in young infants. Our study revealed a decrease in the proportion of Salmonella meningitis from 27% in the first 8 years to 9% in the second 8 years with E. coli replacing Salmonella species as the leading pathogen of this disease during the second period. Overall mortality rate for both periods of time was 11%. However, if we take those with undesirable poor outcomes into account, 43% of patients could be considered treatment failures. The study also reveals a high prevalence of neurological complications when this disease is caused by H. influenzae, S. pneumoniae, and Salmonella species. Stepwise logistic regression analysis revealed that only initial changing levels of consciousness (P = 0.006) were independently associated with treatment failure. The most frequent neurological complications associated with this disease included subdural empyema, hydrocephalus, cerebral infarctions, and seizures. Because therapeutic regimens may require attention to the eradication of bacterial pathogen but also the neurological complications, early diagnosis and choice of appropriate antibiotics are essential to increasing the possibility of survival.

Anti-Bacterial Agents↗
PubMed2004

A clinical and electrophysiologic survey of childhood Guillain-Barré syndrome.

In this 16-year (1986-2001) retrospective study, 23 childhood patients were identified with Guillain-Barré syndrome. According to clinical and electrophysiologic findings, 18 patients manifested acute inflammatory demyelinating polyradiculoneuropathy, 2 had Miller Fisher syndrome, 1 had axonal forms, and 2 were unclassified. Seasonal preponderance was evident in 39% of patients with Guillain-Barré syndrome, developing the disease in the winter (November to January) with upper respiratory infection the most frequent preceding event. The most common manifestation was limb weakness, with various degrees of motor weakness in 22 patients. Bulbar involvement was the most common cranial palsy, and it was evident in 30% of the episodes. Only one of these progressed to mechanical ventilation during hospitalization. Altogether, approximately 61% of the episodes exhibited sensory symptoms. At a follow-up of 1 year or more, 20 patients recovered and 3 had residua. Furthermore, no fatality occurred in our study. Our study also demonstrates that the clinical course of childhood Guillain-Barré syndrome has a shorter recovery time as compared with an adult patient group. Therapeutic outcome is favorable for patients who receive prompt treatment.

Adolescent↗
PubMed2003

Febrile seizures impair memory and cAMP response-element binding protein activation.

The long-term effects of brief but repetitive febrile seizures (FS) on memory have not been as thoroughly investigated as the impact of single and prolonged seizure in the developing brain. Using a heated-air FS paradigm, we subjected male rat pups to one, three, or nine episodes of brief FS on days 10 to 12 postpartum. Neither hippocampal neuronal damage nor apoptosis was noted within 72 hours after FS, nor was there significant hippocampal neuronal loss, aberrant mossy fiber sprouting, or altered seizure threshold to pentylenetetrazol in any FS group at adulthood. The adult rats subjected to nine episodes of early-life FS, however, showed long-term memory deficits as assessed by the Morris water maze. They also exhibited impaired intermediate and long-term memory but spared short-term memory in the inhibitory avoidance task. Three hours after inhibitory avoidance training, phosphorylation of cAMP response-element binding (CREB) protein in the hippocampus was significantly lower in nine-FS-group rats than in controls. Furthermore, rolipram administration, which activated the cAMP-CREB signaling pathway by inhibiting phosphodiesterase type IV, reversed the long-term memory deficits in nine-FS-group rats by enhancing hippocampal CREB phosphorylation. These results raise concerns about the long-term cognitive consequences of even brief frequently repetitive FS during early brain development.

Animals↗
PubMed2003

Neonatal bacterial meningitis in southern Taiwan.

To determine the epidemiologic trends, prognostic factors, and therapeutic results of neonatal bacterial meningitis, 60 neonatal patients with culture-proven neonatal bacterial meningitis were enrolled in this study. To compare changes over time, the appearance of disease among the patients was divided into two equal periods (1986-1993 and 1994-2001). Group B streptococci were the most common causative pathogens, accounting for approximately 32% of the episodes. Escherichia coli, the next most common pathogen, was more frequently observed in the second period. Seventy-seven percent of gram-negative bacilli isolates were resistant to ampicillin. Moreover, oxacillin-resistant Staphylococcus and ampicillin-resistant group B streptococci strains occurred in the second periods as late-onset neonatal bacterial meningitis. The overall mortality rates for the first and second study period were 17% and 8%, respectively. However, if individuals with poor outcomes were taken into account, 38% of patients were considered treatment failures. Significant prognostic factors included the presence of seizures, thrombocytopenia, and high cerebrospinal fluid protein and low cerebrospinal fluid glucose concentration. Although the mortality rate was significantly reduced in the second period, there has been increasing incidence of the emergence of resistant strains presenting a therapeutic challenge. The presentation in neonatal bacterial meningitis might be nonspecific, and blood culture results were negative in 45% of the episodes. Early diagnosis, choice of appropriate antibiotics, and correction of metabolic derangement are essential to improving outcomes.

Chi-Square Distribution↗
PubMed2002

Tuberculous meningitis in infancy.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. To our knowledge, there has been no report in the literature focusing on tuberculous meningitis patients younger than 1 year of age. In this report, we reviewed the clinical features and laboratory findings of seven infants with tuberculous meningitis encountered during a 15-year period. All patients had fever, cough, and alternation of consciousness at presentation. Five patients had bulging anterior fontanel, and five had generalized tonic-clonic seizures. The purified protein derivative skin test was positive in six patients. Six patients had hyponatremia. All seven patients had abnormal cerebrospinal fluid findings, and six of them demonstrated cell counts less than 500 cells/mm(3) with lymphocytic predominance. Brain sonography examination revealed hydrocephalus in all seven patients. Therefore we conclude that antituberculosis therapy should be promptly initiated in any young infant with a clinical impression of meningitis in the context of cerebrospinal fluid white cell count of less than 500 cells/mm(3) and lymphocytic predominance, hyponatremia, and hydrocephalus.

Antitubercular Agents↗
PubMedDate not supplied

Acute flaccid paralysis due to myelopathy in childhood bacterial meningitis.

Spinal cord damage is a rare neurological complication of bacterial meningitis. From 1988 to 2001, three of 186 pediatric patients with acute bacterial meningitis presented with acute flaccid paralysis due to myelopathy. The disease-onset ages and causative pathogens of the three patients were 2 days (group B streptococcus), 3 months (Streptococcus pneumoniae), and 13 years (Neisseria meningitidis), respectively. Spinal MR imaging was normal in the 13-year-old patient, who was left with mild residual motor weakness. Severe necrotizing myelitis and syringomyelia over the thoracic spinal cord were found in the other two younger patients. Both had severe paralysis at follow-up. All three patients required mechanical ventilation or vasopressor agents during antibiotic treatment for bacterial meningitis.

Acute Disease↗