Biochemical markers of perinatal brain damage

Pasquale Florio¹, Raul Abella², Emanuela Marinoni³, Romolo Di Iorio³, Giovanni Li Volti⁴, Fabio Galvano⁴, Giacomo Pongiglione⁵, Alessandro Frigiola², Serena Pinzauti¹, Felice Petraglia¹, Diego Gazzolo^5,6

1Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy, ²Department of Cardiac Surgery S. Donato Milanese University Hospital, S. Donato Milanese, Italy, ³Laboratory of Perinatal Medicine and Molecular Biology, and Department of Internal Medicine University "La Sapienza" Rome, Italy, ⁴Department of Biological Chemistry, Medicinal Chemistry and Molecular Biology, University of Catania, Italy, ⁵Department of Pediatrics, Neuroscience and Cardiovascular Surgery, G. Gaslini Children's Hospital University of Genoa, Genoa - Italy, ⁶Department of Fetal, Maternal and Neonatal Health, G. Garibaldi Hospital Catania , Italy

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Epidemiology of perinatal asphyxia

4. Pathophysiology of brain damage following H-I insult

4.1. Pathogenesis of hypoxic-ischemic cerebral injury

4.2. Delayed (secondary) brain damage

4.3. Excitatory neurotransmitter release

4.4. Formation of free radicals

4.5. Inflammatory mediators

5. Role of Near-Infrared Spectrometry (NIRS) to evaluate the cerebral oxygenation

6. Experimental reports supporting brain damage markers usefulness

6.1. Activin A: in vitro evidence for a H-I-related regulation

6.2. S100B:in vitro evidences for a H-I-related regulation

6.3. Adrenomedullin: in vitro evidences for a H-I-related regulation

6.4. NSE: evidences for a H-I-related regulation

6.5. GFAP: evidences for a H-I-related regulation

7. Clinical data on usefulness of biochemical screening of brain damage

7.1. Activin A as a brain damage marker in infants complicated by H-I reperfusion injury

7.2. S100B as a brain damage marker in infants complicated by I-R injury

7.3. AM as a brain damage marker in infants complicated by H-I reperfusion injury

7.4. NSE as a brain damage marker in infants complicated by H-I reperfusion injury

8. Brain derived protein and the human milk: an evolutionary strategy?

9. Conclusions

10. Acknowledgement

11. References

1. ABSTRACT

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia. To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological