Nejvíce citovaný článek - PubMed ID 28006936
Pathophysiology of perinatal hypoxic-ischemic encephalopathy - biomarkers, animal models and treatment perspectives
Brain injury is a multifaceted condition arising from nonspecific damage to nervous tissue. The resulting cognitive developmental impairments reverberate through patients' lives, affecting their families, and even the broader economic landscape. The significance of early brain injury detection lies in its potential to stave off severe consequences and enhance the effectiveness of tailored therapeutic interventions. While established methods like neuroimaging and neurophysiology serve as valuable diagnostic tools, their demanding nature restricts their accessibility, particularly in scenarios such as small hospitals, nocturnal or weekend shifts, and cases involving unstable patients. Hence, there is a pressing need for more accessible and efficient diagnostic avenues. Among the spectrum of brain injuries, hypoxic-ischemic encephalopathy stands out as a predominant affliction in the pediatric population. Diagnosing brain injuries in newborns presents challenges due to the subjective nature of assessments like Apgar scores and the inherent uncertainty in neurological examinations. In this context, methods like magnetic resonance and ultrasound hold recommendations for more accurate diagnosis. Recognizing the potential of serum biomarkers derived from blood samples, this paper underscores their promise as a more expedient and resource-efficient means of assessing brain injuries. The review compiles current insights into serum biomarkers, drawing from experiments conducted on animal models as well as human brain pathologies. The authors aim to elucidate specific characteristics, temporal profiles, and the available corpus of experimental and clinical data for serum biomarkers specific to brain injuries. These include neuron-specific enolase (NSE), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), and high-mobility-group-protein-box-1 (HMGB1). This comprehensive endeavor contributes to advancing the understanding of brain injury diagnostics and potential avenues for therapeutic intervention.
- MeSH
- biologické markery MeSH
- dítě MeSH
- lidé MeSH
- mozková hypoxie a ischemie * diagnostické zobrazování MeSH
- novorozenec MeSH
- poranění mozku * MeSH
- thiolesterasa ubikvitinu MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
- thiolesterasa ubikvitinu MeSH
The healthy development of the fetus depends on the exact course of pregnancy and delivery. Therefore, prenatal hypoxia remains between the greatest threats to the developing fetus. Our study aimed to assess the impact of prenatal hypoxia on postnatal development and behavior of the rats, whose mothers were exposed to hypoxia (10.5 % O2) during a critical period of brain development on GD20 for 12 h. This prenatal insult resulted in a delay of sensorimotor development of hypoxic pups compared to the control group. Hypoxic pups also had lowered postnatal weight which in males persisted up to adulthood. In adulthood, hypoxic males showed anxiety-like behavior in the OF, higher sucrose preference, and lower levels of grimace scale (reflecting the degree of negative emotions) in the immobilization chamber compared to the control group. Moreover, hypoxic animals showed hyperactivity in EPM and LD tests, and hypoxic females had reduced sociability compared to the control group. In conclusion, our results indicate a possible relationship between prenatal hypoxia and changes in sociability, activity, and impaired emotion regulation in ADHD, ASD, or anxiety disorders. The fact that changes in observed parameters are manifested mostly in males confirms that male sex is more sensitive to prenatal insults.
- MeSH
- acidobazická rovnováha MeSH
- bludiště - učení MeSH
- chování zvířat * MeSH
- gestační stáří MeSH
- hypoxie plodu komplikace patofyziologie MeSH
- modely nemocí na zvířatech MeSH
- pohybová aktivita MeSH
- potkani Wistar MeSH
- preference v jídle MeSH
- senzorimotorický kortex růst a vývoj MeSH
- sexuální faktory MeSH
- sociální interakce MeSH
- těhotenství MeSH
- úleková reakce MeSH
- věkové faktory MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The study examined the morphological and long-term behavioral impacts of neonatal hypoxic-ischemic brain injury in a mouse model. We investigated the modification of different behavioral domains, such as spontaneous climbing, which represents fine motor skills. We also focused on sex-dependent differences during hypoxic-ischemic encephalopathy. The Rice-Vannucci model of hypoxia-ischemia was used, adjusted and adapted to 7-day-old C57BL/6NTac mice. The effects of induced hypoxia and ischemia were also studied separately. At postnatal day 60, mice underwent behavioral testing using the LABORAS apparatus. The perfusion for histological evaluation was performed one day after the behavioral analyses. In groups with separately induced hypoxia or ischemia, the observed alterations in behavior were not accompanied by morphological changes in the cortex or hippocampal formation. Female mice naturally climbed significantly more and hypoxic females reared less than hypoxic males (p<0.05). Male mice postnatally exposed to hypoxia-ischemia exhibited significantly lower vertical activity and higher horizontal activity (p<0.05). Mild hypoxic damage may not be morphologically detectable but may induce substantial behavioral changes in adult mice. There were significant differences between horizontal and vertical activity in reaction to hypoxia-ischemia. Our study indicates that the importance of behavioral testing is irreplaceable and may be reflected in neonatal medicine.
- MeSH
- biomechanika MeSH
- chov zvířat metody MeSH
- chování zvířat * MeSH
- mozková hypoxie a ischemie patofyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- novorozená zvířata MeSH
- poranění mozku patofyziologie MeSH
- sociální izolace * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxic-ischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.
- MeSH
- erythropoetin terapeutické užití MeSH
- hypoxie komplikace farmakoterapie patofyziologie MeSH
- látky tlumící činnost CNS terapeutické užití MeSH
- lidé MeSH
- melatonin terapeutické užití MeSH
- mozková hypoxie a ischemie farmakoterapie etiologie patofyziologie MeSH
- novorozenec MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- erythropoetin MeSH
- látky tlumící činnost CNS MeSH
- melatonin MeSH
Perinatal hypoxia is still one of the greatest threats to the newborn child, even in developed countries. However, there is a lack of works which summarize up-to-date information about that huge topic. Our review covers a broader spectrum of recent results from studies on mechanisms leading to hypoxia-induced injury. It also resumes possible primary causes and observed behavioral outcomes of perinatal hypoxia. In this review, we recognize two types of hypoxia, according to the localization of its primary cause: environmental and placental. Later we analyze possible pathways of prenatal hypoxia-induced injury including gene expression changes, glutaminergic excitatory damage (and a role of NMDA receptors in it), oxidative stress with ROS and RNS production, inflammation and apoptosis. Moreover, we focus on the impact of these pathophysiological changes on the structure and development of the brain, especially on its regions: corpus striatum and hippocampus. These brain changes of the offspring lead to impairments in their postnatal growth and sensorimotor development, and in their motor functions, activity, emotionality and learning ability in adulthood. Later we compare various animal models used to investigate the impact of prenatal and postnatal injury (hypoxic, ischemic or combinatory) on living organisms, and show their advantages and limitations.
- MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- mozek růst a vývoj metabolismus MeSH
- mozková hypoxie metabolismus patologie MeSH
- novorozená zvířata MeSH
- novorozenec MeSH
- oxidační stres fyziologie MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mediátory zánětu MeSH
- receptory N-methyl-D-aspartátu MeSH
Hypoxia is one of the major pathological factors affecting brain function. The aim of the present study was to describe the effect of neonatal hypobaric hypoxia on the behavior of rats and to analyze its effect on hippocampal neurodegeneration. Hypobaric hypoxia at a simulated altitude of 9000 m was induced for one hour in neonatal rat pups (PND7 and PND9) of both sexes. Subsequently, the rats underwent behavioral testing on PND25 and PND35 using a LABORAS apparatus to assess spontaneous behavior. Hypoxia did not cause any morphological damage in the hippocampus of rats. However, hypoxia on PND7 led to less horizontal locomotor activity both, in males (on PND25) and females (on PND35). Hypoxia on PND9 led to higher rearing in females on PND25. Hypoxic males exhibited higher grooming activity, while females lower grooming activity on PND35 following hypoxia induced on PND7. In females, hypoxia on PND9 resulted in higher grooming activity on PND25. Sex differences in the effect of hypoxia was observed on PND35, when hypoxic males compared to hypoxic females displayed more locomotor, rearing and grooming activity. Our data suggest that hypoxia on PND7 versus PND9 differentially affects locomotion and grooming later in adolescence and these effects are sex-dependent.
- MeSH
- hipokampus patologie MeSH
- hypoxie patologie psychologie MeSH
- lokomoce * MeSH
- novorozená zvířata MeSH
- péče o zevnějšek u zvířat * MeSH
- pohlavní dimorfismus MeSH
- potkani Wistar MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH