Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat

Autor: Fabrizio Facchinetti, Nozha Borjini, Alessandro Giuliani, Sandra Sivilia, Mercedes Fernandez, Luciana Giardino, Laura Calzà
Přispěvatelé: Borjini N, Sivilia S, Giuliani A, Fernandez M, Giardino L, Facchinetti F, Calza L.
Rok vydání: 2019
Předmět:
Male
medicine.medical_specialty
Reflex
Startle
Neurology
Time Factors
Immunology
Encephalopathy
Morris water navigation task
Open field
lcsh:RC346-429
Proinflammatory cytokine
03 medical and health sciences
Cellular and Molecular Neuroscience
Random Allocation
0302 clinical medicine
Neonatal hypoxia-ischemia
030225 pediatrics
Internal medicine
medicine
Animals
Rats
Wistar
Maze Learning
Neuroinflammation
lcsh:Neurology. Diseases of the nervous system
business.industry
General Neuroscience
Research
Neurodegeneration
Neurodegenerative Diseases
Inflammatory biomarkers
medicine.disease
Neonatal hypoxia-ischemia
Inflammatory biomarkers
Neurological disorders
3. Good health
Rats
Endocrinology
Animals
Newborn
Hypoxia-Ischemia
Brain
Reflex
Female
Inflammation Mediators
business
030217 neurology & neurosurgery
Biomarkers
Neurological disorders
Zdroj: Journal of Neuroinflammation
Journal of Neuroinflammation, Vol 16, Iss 1, Pp 1-18 (2019)
ISSN: 1742-2094
Popis: Background Hypoxic-ischemic (HI) encephalopathy causes life-long morbidity and premature mortality in term neonates. Therapies in addition to whole-body cooling are under development to treat the neonate at risk for HI encephalopathy, but are not a quickly measured serum inflammatory or neuronal biomarkers to rapidly and accurately identify brain injury in order to follow the efficacy of therapies. Methods In order to identify potential biomarkers for early inflammatory and neurodegenerative events after neonatal hypoxia-ischemia, both male and female Wistar rat pups at postnatal day 7 (P7) were used and had their right carotid artery permanently doubly occluded and exposed to 8% oxygen for 90 min. Sensory and cognitive parameters were assessed by open field, rotarod, CatWalk, and Morris water maze (MWM) test. Plasma and CSF biomarkers were investigated on the acute (24 h and 72 h) and chronic phase (4 weeks). Brains were assessed for gene expression analysis by quantitative RT-PCR Array. Results We found a delay of neurological reflex maturation in HI rats. We observed anxiolytic-like baseline behavior in males more than females following HI injury. HI rats held on the rotarod for a shorter time comparing to sham. HI injury impaired spatial learning ability on MWM test. The CatWalk assessment demonstrated a long-term deficit in gait parameters related to the hind paw. Proinflammatory biomarkers such as IL-6 in plasma and CCL2 and TNF-α in CSF showed an upregulation at 24 h after HI while other cytokines, such as IL-17A and CCL5, were upregulated after 72 h in CSF. At 24 h post-injury, we observed an increase of Edn1, Hif1-α, and Mmp9 mRNA levels in the ipsilateral vs the contralateral hemisphere of HI rats. An upregulation of genes involved with clotting and hematopoietic processes was observed 72 h post-injury. Conclusions Our work showed that, in the immature brain, the HI injury induced an early increased production of several proinflammatory mediators detectable in plasma and CSF, followed by tissue damage in the hypoxic hemisphere and short-term as well as long-lasting neurobehavioral deficits.
Databáze: OpenAIRE
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