Relation of nitric oxide and neonate hypoxic- ischemic encephalopathy

Objective To study the changes of the nitric oxide(NO) in process of neonate hypoxic－ ischemic encephalopathy(HIE) and the relations between the concentrations of NO and HIE. Methods Tested the concentrations of NO in CSF of newborn infants suffered HIE the third day and in plasma of newborn infants suffered HIE just attacked instant(within 2 hours), the first day ,the third day and restoring stage and compared with them of normal contrast term. We tried to analyse the reasons and significance of NO change .Results The NO concentration is the highest in plasma of newborn infants suffered HIE the first day. There is significant difference(P<0.01) after comparing the NO concentrations in plasmas of newborn infants suffered HIE just attacked instant, the first day, the third day with of normal contrast team respectively. But there is not significant difference(P >0.05) between NO in plasmas of restoring stage and of normal contrast team. There is positive correlation between the NO concentration in plasma and in CSF of newborn infants suffered HIE the third day. The more serious the disease is, the higher the NO concentration is, the worse the prognosis is. Conclusion NO play along with the course of HIE and play an important role in neonate HIE. Testing the concentration of NO in plasma and in CSF can also help to judge the degree of disease.

Xuefuzhuyu decoction and astragalus prevent hypoxic-ischemic brain injury

Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The experimental results showed that neuronal morphology and structure recovered, nerve growth factor mRNA expression increased in brain tissues, and neurological function signifi-cantly improved. There was no significant difference in these measures compared with rats treated with Xuefuzhuyu decoction alone or a combined treatment of Xuefuzhuyu decoction with 40 g as-tragalus. These experimental findings revealed that, Xuefuzhuyu decoction combined with astra-galus may up-regulate the expression of nerve growth factor mRNA and accordingly exert a neu-roprotective effect; however, this protection is not dependent on astragalus dosage.

Challenges in developing therapeutic strategies for mild neonatal encephalopathy

There is increasing evidence that infants with mild neonatal encephalopathy(NE) have significant risks of mortality, brain injury and adverse neurodevelopmental outcomes. In the era of therapeutic hypothermia, infants need to be diagnosed within 6 hours of birth, corresponding with the window of opportunity for treatment of moderate to severe NE, compared to the retrospective grading over 2 to 3 days, typically with imaging and formal electroencephalographic assessment in the pre-hypothermia era. This shift in diagnosis may have increased the apparent prevalence of brain damage and poor neurological outcomes seen in infants with mild NE in the era of hypothermia. Abnormal short term outcomes observed in infants with mild NE include seizures, abnormal neurologic examination at discharge, abnormal brain magnetic resonance imaging and difficulty feeding. At 2 to 3 years of age, mild NE has been associated with an increased risk of autism, language and cognitive deficits. There are no approved treatment strategies for these infants as they were not included in the initial randomized controlled trials for therapeutic hypothermia. However, there is already therapeutic creep, with many centers treating infants with mild NE despite the limited evidence for its safety and efficacy. The optimal duration of treatment and therapeutic window of opportunity for effective treatment need to be specifically established for mild NE as the evolution of injury is likely to be slower, based on preclinical data. Randomized controlled trials of therapeutic hypothermia for infants with mild NE are urgently required to establish the safety and efficacy of treatment. This review will examine the evidence for adverse outcomes after mild NE and dissect some of the challenges in developing therapeutic strategies for mild NE, before analyzing the evidence for therapeutic hypothermia and other strategies for treatment of these infants.

Chinese Herbal Medicine Xingnaojing Injection(醒脑静注射液) for Hypoxic Ischemic Encephalopathy in Newborns:A Systematic Review and Meta-Analysis

Objectives： To evaluate the efficacy and safety of Chinese herbal medicine Xingnaojing Injection（醒脑静注射液） for newborns with hypoxic ischemic encephalopathy（HIE）. Methods： Literature was identified by searching the Pub Med, EMBASE, Cochrane Library, Cochrane Central, and four Chinese literature databases from the establishment of database to October in 2013. Relevant reference lists were also screened. Two reviewers independently evaluated the methodological quality of included studies. We also conducted the meta-analysis. Results： Thirteen trials involving 1,169 patients were included. There was no trial reported death or disability at the end of follow-up period. Meta-analysis of 4 trials（n=371） showed that there was no significant difference in the reduction of mortality [risk ratios（RR）=0.48, 95% confidence intervals（CI, 0.21, 1.13）, P=0.09] between the Xingnaojing and control groups. Meta-analysis of 5 trials（n=359） showed that there was significant difference in reducing the major neurodevelopmental disability [RR=0.36, 95% CI（0.19, 0.66）, P=0.001]. Meta-analysis of 6 trials（n=447） showed that there was a significant difference in the author self-defined symptom improvement [RR=1.25, 95% CI（1.14, 1.37）, P〈0.01]. No fatal side-effects were reported. Conclusion： Based on the limited evidence, the routine use of Xingnaojing Injection for treatment of HIE in newborns is not recommended. Further well-conducted trials are justified.

The neuroprotective effect of mesenchymal stem cells is mediated through inhibition of apoptosis in hypoxic ischemic injury

Background Neonatal hypoxia ischemia causes severe brain damage.Stem cell therapy is a promising method for treating neuronal diseases.Clinical translation of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)for the recovery of neurons after hypoxic ischemic encephalopathy(HIE)may represent an effective therapy.Methods Primary neurons were exposed to oxygen-glucose deprivation(OGD)and subsequently cocultured with UC-MSCs.Apoptosis was examined by Annexin V-FITC-PI.Genes related to apoptosis were detected using RT-PCR and westernblot analyses.Using an in vivo model,HIE was induced in postnatal day 7 mice,and UC-MSCs were transplanted via the intraventricular route.UC-MSC migration was investigated by immunofluorescence,and lesion volumes were measured by TTC staining.Apoptosis in injured brain cells was detected by the TUNEL assay.RT-PCR and ELISA were used to detect the expression of inflammatory factors in cells and animal tissues.Results Flow cytometry analysis revealed that apoptosis in injured neurons was inhibited by UC-MSCs.The RT-PCR and western blot results indicated that coculture inhibited the expression of proapoptotic genes and upregulated expression of antiapoptotic genes.In the animal model,transplanted UC-MSCs migrated toward the cerebral lesion site and decreased the lesion extent in HIE.TUNEL staining showed that the MSC group exhibited significantly reduced numbers of TUNEL-positive cells.RT-PCR and ELISA showed that UC-MSCs inhibited the upregulation of TNF-αand IL-1βin response to hypoxic ischemic injury.Conclusion These results indicate that UC-MSCs exert neuroprotective effects against hypoxic ischemic injury by inhibiting apoptosis,and the mechanism appears to be through alleviating the inflammatory response.

Targeted temperature management in neurological intensive care unit

Targeted temperature management(TTM) shows the most promising neuroprotective therapy against hypoxic/ischemic encephalopathy(HIE).In addition, TTM is also useful for treatment of elevated intracranial pressure(ICP).HIE and elevated ICP are common catastrophic conditions in patients admitted in Neurologic intensive care unit(ICU).The most common cause of HIE is cardiac arrest.Randomized control trials demonstrate clinical benefits of TTM in patients with post-cardiac arrest.Although clinical benefit of ICP control by TTM in some specific critical condition, for an example in traumatic brain injury, is still controversial, efficacy of ICP control by TTM is confirmed by both in vivo and in vitro studies.Several methods of TTM have been reported in the literature.TTM can apply to various clinical conditions associated with hypoxic/ischemic brain injury and elevated ICP in Neurologic ICU.

Neonatal infratentorial subdural hematoma contributing to obstructive hydrocephalus in the setting of therapeutic cooling: A case report

BACKGROUND Symptomatic neonatal subdural hematomas usually result from head trauma incurred during vaginal delivery,most commonly during instrument assistance.Symptomatic subdural hematomas are rare in C-section deliveries that were not preceded by assisted delivery techniques.Although the literature is inconclusive,another possible cause of subdural hematomas is therapeutic hypothermia.CASE SUMMARY We present a case of a term neonate who underwent therapeutic whole-body cooling for hypoxic ischemic encephalopathy following an emergent C-section delivery for prolonged decelerations.Head ultrasound on day of life 3 demonstrated a rounded mass in the posterior fossa.A follow-up brain magnetic resonance imaging confirmed hypoxic ischemic encephalopathy and clarified the subdural hematomas in the posterior fossa causing mass effect and obstructive hydrocephalus.CONCLUSION The aim of this report is to highlight the rarity and importance of mass-like subdural hematomas causing obstructive hydrocephalus,particularly in the setting of hypoxic ischemic encephalopathy and therapeutic whole-body cooling.

Comments on"Neonatal infratentorial subdural hematoma contributing to obstructive hydrocephalus in the setting of therapeutic cooling:A case report"

Although therapeutic hypothermia(TH)contributes significantly in the treatment of hypoxic ischemic encephalopathy(HIE),it could result in devastating complications such as intracranial hemorrhages.Laboratory examinations for possible coagulation disorders and early brain imaging can detect all these cases that are amenable to aggravation of HIE after the initiation of TH.