Guanosine Protects Against Traumatic Brain Injury-Induced Functional Impairments and Neuronal Loss by Modulating Excitotoxicity, Mitochondrial Dysfunction, and Inflammation

• Published in: Molecular neurobiology 2017-12, Vol.54 (10), p.7585-7596
• Main Authors: Gerbatin, Rogério da Rosa, Cassol, Gustavo, Dobrachinski, Fernando, Ferreira, Ana Paula O., Quines, Caroline B., Pace, Iuri D. Della, Busanello, Guilherme L., Gutierres, Jessié M., Nogueira, Cristina W., Oliveira, Mauro S., Soares, Félix A., Morsch, Vera M., Fighera, Michele R., Royes, Luiz Fernando F.
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Brain; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Brain Injuries, Traumatic - prevention & control; Caspase; Caspase-3; Cell Biology; Cell Count - methods; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Clinical trials; Drug development; Edema; Excitotoxicity; Glutamate-ammonia ligase; Glutamine; Guanosine; Guanosine - pharmacology; Guanosine - therapeutic use; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammation - prevention & control; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Inflammatory response; Male; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Na+/K+-exchanging ATPase; Neurobiology; Neurological complications; Neurology; Neurons; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Nucleosides; Percussion; Rats; Rats, Wistar; Rodents; Toxicity; Traumatic brain injury
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-0238-z

Traumatic brain injury (TBI) is one of the most common types of brain injuries that cause death or persistent neurological disturbances in survivors. Most of the promising experimental drugs were not effective in clinical trials; therefore, the development of TBI drugs represents a huge unmet need. Guanosine, an endogenous neuroprotective nucleoside, has not been evaluated in TBI to the best of our knowledge. Therefore, the present study evaluated the effect of guanosine on TBI-induced neurological damage. Our findings showed that a single dose of guanosine (7.5 mg/kg, intraperitoneally (i.p.) injected 40 min after fluid percussion injury (FPI) in rats protected against locomotor and exploratory impairments 8 h after injury. The treatment also protected against neurochemical damage to the ipsilateral cortex, glutamate uptake, Na + /K + -ATPase, glutamine synthetase activity, and alterations in mitochondrial function. The inflammatory response and brain edema were also reduced by this nucleoside. In addition, guanosine protected against neuronal death and caspase 3 activation. Therefore, this study suggests that guanosine plays a neuroprotective role in TBI and can be exploited as a new pharmacological strategy.