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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Fibroblast growth factor 2 improves cognitive function in neonatal rats with hypoxic ischaemic brain injury
Yalcin Celik1, Bora Resitoglu2, Mustafa Komur3
1Department of Neonatology, Mersin, Turkey.
Insights
Fibroblast growth factor 2 (FGF2) treatment reduced brain injury and improved cognitive function in neonatal rats. FGF2 demonstrated a dose-dependent effect, enhancing performance in the Morris water maze test.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Hypoxic-ischaemic brain injury (HIBI) is a significant cause of neonatal mortality and long-term neurological deficits.
- Fibroblast growth factor 2 (FGF2) is a potent growth factor with known neuroprotective and regenerative properties.
- Investigating FGF2's therapeutic potential in neonatal HIBI models is crucial for developing novel treatment strategies.
Purpose of the Study:
- To evaluate the efficacy of fibroblast growth factor 2 (FGF2) in mitigating neuronal apoptosis and improving cognitive function following experimentally induced hypoxic-ischaemic brain injury (HIBI) in neonatal rats.
- To determine the dose-dependent effects of FGF2 administration on neuroprotection and cognitive recovery.
Main Methods:
- A randomized controlled study involving 7-day-old male rats subjected to HIBI via carotid artery ligation and hypoxia.
- Administration of two doses of FGF2 (20 ng/g and 40 ng/g) or saline (control) via intraperitoneal injection.
- Assessment of neuronal apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) assay.
- Evaluation of cognitive function using the Morris water maze (MWM) test at 14 weeks of age.
Main Results:
- FGF2 treatment significantly reduced the number of apoptotic neurons in the injured hemisphere compared to the control group (p<0.001).
- A higher dose of FGF2 (40 ng/g) resulted in a more significant reduction in neuronal apoptosis than the lower dose (20 ng/g) (p<0.001).
- FGF2 administration dose-dependently improved cognitive performance in the Morris water maze test.
Conclusions:
- Fibroblast growth factor 2 (FGF2) effectively reduces neuronal apoptosis in neonatal rats with HIBI.
- FGF2 treatment significantly enhances cognitive function in a dose-dependent manner following HIBI.
- FGF2 represents a promising therapeutic agent for managing neonatal hypoxic-ischaemic brain injury and its long-term cognitive consequences.
Objective:
To determine the effect of fibroblast growth factor 2 on cognitive function in neonatal rats with hypoxic-ischaemic brain injury.
Methods:
The randomised controlled study was conducted from January to June 2011 at Mersin University, School of Medicine, Experimental Animals Research Laboratory and Physiology Behaviour Laboratory, Mersin, Turkey. It included 7-d-old male rats that were randomised into four groups: fibroblast growth factor 2-20, fibroblast growth factor 2-40, control and sham. All the rats, except those in the sham group, were kept in a hypoxia chamber containing 8% oxygen for 2 hours following ligation of the right carotid artery. After hypoxic-ischaemic brain injury was induced, 20 ng g-1 or 40 ng g-1 of fibroblast growth factor 2 was administered via the intraperitoneal route. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling method was used to evaluate neuronal apoptosis. The Morris water maze (MWM) test was administered to the rats at age 14 weeks.
Results:
Of the 78 rats on the study, 18 (23%) were in the sham group, while the other three groups had 20 (25.6%) rats each. The number of apoptotic neurons in the right hemisphere in the experimental groups was significantly lower than in the control group (p=0.004 and p<0.001). The number of apoptotic neurons in the right hemisphere in the fibroblast growth factor 2-40 group was significantly lower than in the fibroblast growth factor 2-20 group (p<0.001). Moreover, fibroblast growth factor 2improved Morris water maze test cognitive performance in a dose-dependent manner.
Conclusions:
Fibroblast growth factor 2 treatment reduced neuronal apoptosis and improved cognitive functioning in neonatal rats with experimentally-induced hypoxic-ischaemic brain injury.
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