Inhibition of Inducible Nitric Oxide Synthase Attenuates Deficits in Synaptic Plasticity and Brain Functions Following Traumatic Brain Injury
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Traumatic brain injury (TBI), resulting from external force on the head, usually leads to long-term deficits in motor and cognitive functions. Inducible nitric oxide synthase (iNOS)-mediated excessive inflammation could exacerbate brain damage after TBI. The present study therefore investigated the potential neuroprotective effects of iNOS inhibition after TBI. Male C57BL/6J mice were subjected to controlled cortical impact injury and then treated with high selective iNOS inhibitor 1400W. Expression of iNOS mRNA was determined by quantitative RT-PCR. Western blotting was carried out to determine iNOS protein levels. Motor and cognitive functions, and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC) and hippocampus were examined. Expression of iNOS was induced after TBI in a temporal manner. Treatment with 1400W after TBI improved motor and cognitive functions. TBI mice showed deficits in LTP in both the mPFC and hippocampus, and treatment with 1400W could rescue this impairment. Inhibition of iNOS attenuated deficits in synaptic plasticity and brain functions after TBI. The neuroprotective effect of iNOS inhibition on cognitive function might be via rescuing the TBI-induced LTP impairment.
KeywordsTraumatic brain injury (TBI) Neuroprotection Inhibitor Inducible nitric oxide synthase (iNOS) Behaviors
Compliance with Ethical Standards
Research Involving Human Participants and/or Animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Conflict of Interest
The authors declare that they have no conflict of interest.
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