Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Longitudinally tracking personal physiomes for precision management of childhood epilepsy.

Our current understanding of human physiology and activities is largely derived from sparse and discrete individual clinical measurements. To achieve precise, proactive, and effective health management of an individual, longitudinal, and dense tracking of personal physiomes and activities is required, which is only feasible by utilizing wearable biosensors. As a pilot study, we implemented a cloud computing infrastructure to integrate wearable sensors, mobile computing, digital signal processing, and machine learning to improve early detection of seizure onsets in children. We recruited 99 children diagnosed with epilepsy and longitudinally tracked them at single-second resolution using a wearable wristband, and prospectively acquired more than one billion data points. This unique dataset offered us an opportunity to quantify physiological dynamics (e.g., heart rate, stress response) across age groups and to identify physiological irregularities upon epilepsy onset. The high-dimensional personal physiome and activity profiles displayed a clustering pattern anchored by patient age groups. These signatory patterns included strong age and sex-specific effects on varying circadian rhythms and stress responses across major childhood developmental stages. For each patient, we further compared the physiological and activity profiles associated with seizure onsets with the personal baseline and developed a machine learning framework to accurately capture these onset moments. The performance of this framework was further replicated in another independent patient cohort. We next referenced our predictions with the electroencephalogram (EEG) signals on selected patients and demonstrated that our approach could detect subtle seizures not recognized by humans and could detect seizures prior to clinical onset. Our work demonstrated the feasibility of a real-time mobile infrastructure in a clinical setting, which has the potential to be valuable in caring for epileptic patients. Extension of such a system has the potential to be leveraged as a health management device or longitudinal phenotyping tool in clinical cohort studies.

Acute Flaccid Myelitis in Children in Zhejiang Province, China.

In July-December 2018, an outbreak of polio-like acute flaccid myelitis (AFM) occurred in Zhejiang province, China. Enterovirus (EV)-D68 infection has been reported to be associated with AFM. This study aimed to investigate the clinical presentation, laboratory findings, and outcomes of AFM patients. We investigated the clinical and virologic information regarding the AFM patients, and real-time PCR, sequencing, and phylogenetic analysis were used to investigate the cause of AFM. Eighteen cases met the definition of AFM, with a median age of 4.05 years (range, 0.9-9 years), and nine (50%) were EV-D68 positive. Symptoms included acute flaccid limb weakness and cranial nerve dysfunction. On magnetic resonance imaging, 11 (61.1%) patients had spinal gray matter abnormalities. Electromyography results of 16 out of 17 patients (94.1%) were abnormal. Cerebrospinal fluid (CSF) pleocytosis was common (94.4%), while CSF protein concentration was normal in all patients. There was little improvement after early aggressive therapy. Phylogenetic analysis revealed that EV-D68 subclade B3 was the predominant lineage circulating in Zhejiang province in 2018.

[A genotyping study of 13 cases of early-onset Charcot-Marie-Tooth disease].

OBJECTIVE: To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT). METHODS: Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed. RESULTS: A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C>G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A>G (p.K109R) of the MFN2 gene was rated as "pathogenic". CONCLUSIONS: Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) associated with bacteria meningitis caused by listeria monocytogenes: A case report.

RATIONALE: Mild encephalitis/encephalopathy with a reversible splenial lesion is a clinico-radiological syndrome mainly triggered by viral infection. Bacteria, like listeria monocytogenes, are relatively rare pathogens. PATIENT CONCERNS: A two and a half years old girl with a 3-day history of fever and vomiting, complicated by a sudden seizure. She was in a coma after seizure. DIAGNOSES: Listeria monocytogenes was detected in cerebrospinal fluid cultures. Serum IL-6 remarkably elevated, and hyponatremia appeared on day 2 of hospitalization. Magnetic resonance imaging of the brain performed on day 3 of hospitalization showed right subdural effusion and a lesion in the central portion of the splenium of the corpus callosum. INTERVENTIONS: We administered antimicrobial therapy, intravenous mannitol and hypertonic fluid therapy. OUTCOMES: Her neurological symptoms improved gradually. The lesion in the splenium of the corpus callosum completely disappeared on magnetic resonance imaging on day 10 of hospitalization. LESSONS: We diagnosed this case as mild encephalitis/encephalopathy with a reversible splenial lesion caused by listeria monocytogenes. The patient recovered completely clinically and on imaging, without any specific immunomodulatory treatment. It also indicated IL-6 may play a role in the forms of hyponatremia in mild encephalitis/encephalopathy with a reversible splenial lesion.

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing.

Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children. Here we conducted a targeted exome-sequencing of 63 trios of Chinese epilepsy families using a custom-designed NGS panel that covers 412 known and candidate genes for epilepsy. We identified pathogenic and likely pathogenic variants in 15 of 63 (23.8%) families in known epilepsy genes including SCN1A, CDKL5, STXBP1, CHD2, SCN3A, SCN9A, TSC2, MBD5, POLG and EFHC1. More importantly, we identified likely pathologic variants in several novel candidate genes such as GABRE, MYH1, and CLCN6. Our results provide the evidence supporting the application of custom-designed NGS panel in clinic and indicate a conserved genetic susceptibility for epilepsy between Chinese and Caucasian children.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with Mycoplasma pneumoniae infection.

BACKGROUND: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by transient mild symptoms of encephalopathy and a reversible lesion in the splenium of the corpus callosum on magnetic resonance imaging (MRI). It is often triggered by infection. The common pathogens of MERS are viruses, especially influenza virus. However, Mycoplasma pneumoniae (M.pneumoniae) are relatively rare pathogens for MERS. CASE PRESENTATION: Here we report two paediatric cases of M.pneumoniae infection-induced MERS. The diagnosis of M.pneumoniae infection was established based on polymerase chain reaction (PCR) and specific serum antibodies (IgM). Both of the two patients presented with mild encephalopathy manifestations and recovered completely within a few days. The initial MRI showed a lesion in the central portion of the splenium of the corpus callosum, which completely resolved on the seventh and eighth day after admission for case 1 and case 2. Lumbar puncture was performed in both patients, which revealed no pleocytosis. In case 1, the patient had hyponatremia, peripheral facial nerve paralysis, and rash. To the best of our knowledge, it is the first MERS case associated with peripheral nerve damage. In case 2, interleukin-6(IL-6) was moderately increased in the cerebrospinal fluid (CSF). It suggested that IL-6 may play a role in the pathogenesis of M.pneumoniae-induced MERS. CONCLUSION: Our study enriches the available information on the pathogens of MERS and provides valuable data for better understanding of this syndrome.

Cerebral Sparganosis in Children: Epidemiologic and Radiologic Characteristics and Treatment Outcomes: A Report of 9 Cases.

BACKGROUND: Pediatric cerebral sparganosis has been seldom reported. In the current study, we retrospectively reviewed the clinicopathologic records of 9 consecutive pediatric cases of cerebral sparganosis and analyzed their epidemiologic characteristics and clinical outcomes. METHODS: Our cases included 6 boys and 3 girls, all from rural areas, and their median age at diagnosis was 9.4 (range, 5.8-12.9) years. The median duration of symptoms from onset to definite diagnosis was 21 months (range, 1 week to 3.7 years). RESULTS: Enzyme-linked immunosorbent assay revealed that serum anti-sparganosis antibody was positive in 9 of 9 patients and cerebrospinal fluid anti-sparganosis antibody was positive in 4 of 6 patients. Eight patients underwent craniotomy the removal of worms. The patients also received oral praziquantel. They were followed up for 2.2 years to 4.4 years. One patient died, and 8 patients survived. Three cases had poor outcomes whereas the outcome of the remaining 5 cases was satisfactory. CONCLUSIONS: Children are more at risk for sparganosis and cerebral sparganosis may be missed because of unclear epidemiologic history and nonspecific manifestations. Cerebrospinal fluid eosinophil counts and enzyme-linked immunosorbent assay for anti-sparganosis antibody and computed tomography/magnetic resonance imaging scans may be relied on for an early and accurate diagnosis before surgery.

Acute Blockage of Notch Signaling by DAPT Induces Neuroprotection and Neurogenesis in the Neonatal Rat Brain After Stroke.

Notch signaling is critically involved in various biological events. Notch undergoes cleavage by the γ-secretase enzyme to release Notch intracellular domain that will translocate into nucleus to result in expression of target gene. γ-Secretase inhibitors have been developed as potential treatments for neurological degenerative diseases, but its effects against ischemic injury remain relatively uncertain. In the present study, we demonstrated that N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor not only rescued the cerebral hypoperfusion or ischemia neonatal rats from death, reduced apoptosis in penumbra, but also reduced brain infarct size. Furthermore, DAPT elicited some morphologic hallmarks such as neurogenesis and angiogenesis that related to the brain repair and functional recovery after stroke: increased accumulations of newborn cells in the peri-infarct region with a higher fraction of them adopting immature neuronal and glial markers instead of microglial markers on 5 days, enhanced vascular densities in penumbra at 14 days, and evident regulations of the gene profiles associated with neurogenesis in penumbral tissues. The current results suggest that DAPT is a potential neuroprotectants against ischemic injury in immature brain, and future treatment strategies such as clinical trials using γ-secretase inhibitors would be an attractive therapy for perinatal ischemia.

Reversible bilateral striatal lesions following Mycoplasma pneumoniae infection associated with elevated levels of interleukins 6 and 8.

BACKGROUND: Reversible bilateral striatal necrosis associated with Mycoplasma pneumoniae (M. pneumoniae) infection is a rare neurological disease. The exact pathogenic mechanism remains unknown. PATIENT: We report reversible bilateral striatal lesions with a favorable outcome secondary to M. pneumoniae infection in an 8-year-old Chinese girl. Cranial MRI showed abnormal signals in bilateral striatum, which disappeared 8 months later. To better understand the pathogenesis of this encephalopathy, we examined cytokines levels in serum and cerebrospinal fluid from this patient. The results revealed the concentrations of interleukin-6 and interleukin-8 increased significantly in serum (26 pg/mL and 66 pg/mL, respectively) and cerebrospinal fluid (122 pg/mL and 325 pg/mL, respectively), and were reduced markedly after the therapy. Intrathecal production of interleukin-6 and interleukin-8 is probably related to the pathogenesis of striatal lesions caused by M. pneumoniae. These cytokines may cause local vascular injury, and finally leading to local vascular occlusion. CONCLUSION: Our results suggest that interleukin-6 and interleukin-8 may play important roles in the pathogenesis of this disease. This is the first report to describe the role of cytokines in this condition and relevant literature is reviewed. Our findings may lead to better understanding of the pathogenesis of M. pneumoniae-associated striatal lesions.

Novel mutations of the ATP7B gene in Han Chinese families with pre-symptomatic Wilson's disease.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism, caused by mutations in the ATP7B gene, resulting in copper accumulation in the liver, brain, kidney, and cornea and leading to significant disability or death if untreated. Early diagnosis and proper therapy usually predict a good prognosis, especially in pre-symptomatic WD. Genetic testing is the most accurate and effective diagnostic method for early diagnosis. METHODS: The clinical and biochemical features of three unrelated Han Chinese families with pre-symptomatic WD were reported. The molecular defects in these families were investigated by polymerase chain reaction and DNA sequencing. Hundred healthy children with the same ethnic background served as controls. Bioinformatic tools (polymorphism phenotyping-2, sorting intolerant from tolerant, protein analysis through evolutionary relationships, and predictor of human deleterious single nucleotide polymorphisms) were combined and used to predict the functional effects of mutations. RESULTS: We identified 2 novel ATP7B mutations (p.Leu692Pro and p.Asn728Ser) and 3 known mutations (p.Met769fs, p.Arg778Leu and p.Val1216Met) in these Chinese WD families. These mutations were not observed in the 100 normal controls. The bioinformatic method showed that p.Leu692Pro and p.Asn728Ser mutations are pathogenic. CONCLUSIONS: Our research enriches the mutation spectrum of the ATP7B gene worldwide and provides valuable information for studying the mutation types and mode of inheritance of ATP7B in the Chinese population. Liver function analysis and genetic testing in young children with WD are necessary to shorten the time to the initiation of therapy, reduce damage to the liver and brain, and improve prognosis.

Inhibition of MAPK/ERK signaling blocks hippocampal neurogenesis and impairs cognitive performance in prenatally infected neonatal rats.

Hippocampus endogenous neurogenesis has been postulated to play a favorable role in brain restoration after injury. However, the underlying molecular mechanisms have been insufficiently deciphered. Here we investigated the potential regulatory capacity of MAPK/ERK signaling on neurogenesis and the associated cognitive performance in prenatally infected neonatal rats. From our data, intrauterine infection could induce hippocampal neuronal apoptosis and promote endogenous repair by evoking neural stem cell proliferation and survival. We also found intrauterine infection could induce increased levels of p-ERK, p-CREB and BDNF, which might be responsible for the potential endogenous rescue system. Furthermore, inhibition of MAPK/ERK signaling could aggravate hippocampal neuronal apoptosis, decrease neurogenesis, and impair the offspring's cognitive performances and could also down-regulate the levels of p-ERK, p-CREB and BDNF. Our data strongly suggest that the activation of MAPK/ERK signaling may play a significant role in promoting survival of newly generated neural stem cells via an anti-apoptotic mechanism, which may be particularly important in endogenous neuroprotection associated with cognitive performance development in prenatally infected rats.

Guillain-Barré Syndrome in a Boy With Lung Fluke Infection: Case Report and Literature Review.

Guillain-Barré syndrome is the most common acute peripheral neuropathy in children in most countries. The cause and pathogenesis of the disease have yet to be clarified. There have been only a few reports of Guillain-Barré syndrome resulting from parasite infections worldwide, no cases of Guillain-Barré syndrome after lung fluke infection have been reported. We report a case of an 8-year-old male patient with Guillain-Barré syndrome after lung fluke infection. The child had a history of consumption of undercooked crabs. He was diagnosed with paragonimiasis. The patient experienced paralysis of and pain in the lower limbs about 3 weeks after symptom onset. Neurologic and electrophysiologic examination findings supported the diagnosis of Guillain-Barré syndrome. Parasitic infections should also be considered when determining which antecedent infection is associated with Guillain-Barré syndrome.

Regulation of gap junctional communication by astrocytic mitochondrial K(ATP) channels following neurotoxin administration in in vitro and in vivo models.

It is known that neuronal ATP-sensitive potassium (K(ATP)) channels and astrocytic gap junctions (GJs) are involved in the mechanism underlying neurodisorders. The K(ATP) channels exist also in glial cells, and the objective of this study was to determine whether the astrocytic K(ATP) channels exert their effect on neurotoxin-induced neurodysfunction through regulating the astrocytic GJ function. The results showed that diazoxide, a selective mitochondrial K(ATP) (mitoK(ATP)) channel opener, enhanced the GJ coupling, but 5-hydroxydecanoate, a selective mitoK(ATP) channel blocker that significantly inhibits GJ coupling in vitro did not. Activation of astrocytic mitoK(ATP) channels alleviated kainic acid-induced dysfunction of GJ intercellular communication. Finally, activation of mitoK(ATP) channels improved the astrocytic GJ coupling in the hippocampus after seizures due to the colabeling of GJ subunit connexin 43 and connexin 45 with glial marker and was increased substantially by the administration of diazoxide. Western blot demonstrated that the mitoK(ATP) channels regulated the expression of connexin 43 (P2; active form) and connexin 45 in the epileptic hippocampus. These findings demonstrate that activation of astrocytic mitoK(ATP) channels improves the GJ function in astrocytes, indicating that the effect of the astrocytic mitoK(ATP) channels on neurotoxin-induced neurodysfunction might be, in part, through the regulation of the GJ-coupled spatial buffering in the hippocampus.

The role of an Ommaya reservoir in the management of children with cryptococcal meningitis.

Cryptococcal meningitis is the most common life-threatening fungal infection and is associated with high mortality in children. Amphotericin B plus flucytosine and fluconazole is the optimal current therapy. Implantation of an Ommaya reservoir for intraventricular infusion of medication and aspiration of cerebrospinal fluid (CSF) for the treatment of increased intracranial pressure (ICP) has been reported. Intraventricular injection of amphotericin B through an Ommaya reservoir in children with cryptococcal meningitis has not been reported previously. We report two children who had cryptococcal meningitis and associated increased intracranial pressure, and were treated with an Ommaya reservoir. Both patients experienced rapid reversal of symptoms. At the time of discharge both patients had recovered and have remained asymptomatic.

Effects of topiramate on weight and metabolism in children with epilepsy.

AIM: To explore the mechanism of topiramate-induced weight loss in epilepsy children by monitoring metabolism indices. METHODS: Children with epilepsy were treated with topiramate at their first clinical visit. Metabolism indices including body mass index (BMI) and its SD scores, leptin, adiponectin, leptin/adiponectin (L/A), lipid profile-insulin and Homeostasis Model Assessments (HOMA) index were collected before and after treatment. RESULTS: Topiramate treatment significantly reduced L/A (t = 2.156, p = 0.031), and markedly increased the serum level of adiponectin (t = 3.124, p = 0.002). Moreover, there were no relationships between the metabolism indices and dosages of topiramate (p > 0.05). CONCLUSION: Our studies find that topiramate treatment in epilepsy children increases energy metabolism, resulting in weight loss. It has been demonstrated that adiponectin play a significant role in metabolic regulations.

[Cannabinoid receptor 1 expression and pathological changes in rat hippocampus after deprivation of rapid eye movement sleep].

OBJECTIVE: To observe the expression of cannabinoid receptor 1 (CB1R) mRNA and pathological changes in rat hippocampus after deprivation of rapid eye movement (REM) sleep. METHODS: Totally 42 Sprague-Dawley male rats were randomly divided into cage control (CC), tank control (TC) and the sleep deprivation groups (SD). The SD and TC rats were sacrificed at the end of 1 d, 3 d and 5 d sleep deprivation periods, respectively. The modified multiple platform methods were established for the REM sleep deprivation. CB1R mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). The hippocampus sections of different stages were observed with electron microscope. RESULT: In SD 1 d group, the expression of CB1R mRNA was significantly increased compared with the CC, TC, SD 3 d and SD 5 d groups (P <0.05) while in SD 3 d group it was reduced. The expression of CB1R mRNA of SD 5 d group was significantly higher than that of the SD 3 d group (P <0.05). Neuron apoptosis was found in SD 3 d and SD 5 d groups. CONCLUSION: Sleep deprivation can cause brain injury with the changes of CB1R mRNA expression.

Activation of ATP-sensitive potassium channels prevents the cleavage of cytosolic mu-calpain and abrogates the elevation of nuclear c-Fos and c-Jun expressions after hypoxic-ischemia in neonatal rat brain.

The purpose of this study was to determine whether activation of ATP-sensitive K+ (KATP) channels with diazoxide (DIZ) is able to prevent the cleavage of cytosolic mu-calpain and abrogate the elevation of nuclear c-Fos and c-Jun protein (c-Fos, c-Jun) expressions after hypoxic-ischemia (HI) in brain. The model of hypoxic-ischemic brain injury (HIBI) was made in the 7-day-old Sprague-Dawley (SD) rats by left carotid arterial ligation and hypoxia (8% oxygen). DIZ was injected into the left lateral ventricle (5 microl, 1 mg/ml) before or post-hypoxic-ischemia (HI) insults. Western blot and computer image processing were used to detect the integrated density of nuclear c-Fos and c-Jun at 4 h and cleavage of cytosolic mu-calpain at 24 h after HI insults from cerebral cortical and hippocampal samples. Compared with HI controls (c-Fos=30.37+/-7.39 from cortical samples, 58.61+/-3.64 from hippocampal samples; c-Jun=52.48+/-14.23 from cortical samples, 35.55+/-4.73 from hippocampal samples), there was a significant down-regulation of c-Fos and c-Jun expressions from cortical and hippocampal samples in rats treated with DIZ before (c-Fos=11.10+/-4.64 from cortical samples, 4.82+/-3.38 from hippocampal samples; c-Jun=19.01+/-5.29 from cortical samples, 35.55+/-4.73 from hippocampal samples) or post- (c-Fos=18.81+/-7.93 from cortical samples, 11.33+/-7.05 from hippocampal samples; c-Jun=24.64+/-10.01 from cortical samples, 19.75+/-3.47 from hippocampal samples) HI insults. Furthermore, the ratio of 76 kD/80 kD of mu-calpain was down-regulated from cortical and hippocampal samples in rats treated with DIZ before or post-HI insults, demonstrating a significant difference compared with that observed in HI controls. Finally, the increase in DNA fragments caused by the HI injury was decreased or eliminated by the treatment with DIZ. These data suggests that activation of KATP channels by DIZ reduces the degree of mu-calpain proteolysis, and c-Fos and c-Jun expressions in immature brain may contribute to the neuroprotection of K(ATP) channel openers against HIBI.