Introduction: Inducible nitric oxide synthase (iNOS) is upregulated by cytokines and is detected in brain during the acute inflammatory response to traumatic brain injury (TBI).1 In sepsis models, iNOS-derived nitric oxide (NO) prevents apoptosis in hepatocytes2 while in stroke, it is detrimental.3 We studied the role of iNOS in TBI using two methods; 1) treatment of rats with iNOS inhibitors aminoguanidine (AG) or N-iminoethyl-D-lysine (NIL), and 2) assessment of knockout mice lacking the gene for iNOS (knockout, -/-). Methods: Male Sprague-Dawley rats (n=10/grp), underwent controlled cortical impact (CCI) with secondary hypoxemia (FiO2 = 0.11 for 30 min).4 After injury, Alzet pumps were implanted SQ to deliver AG (∼180 mg/kg/d), NIL (∼60 mg/kg/d) or saline vehicle. In male mice (n=8/grp), CCI was performed in iNOS (-/-) and wild type (+/+) littermates. Outcome parameters included motor function and memory acquisition (Morris water maze [MWM], as well as histology (contusion volume and hippocampal neuron counts). Results: In rats, treatment with AG or NIL exacerbated damage in CA1 and CA3 (p < 0.05 vs vehicle) but did not expand the contusion. iNOS (/-) mice showed markedly increased latency in MWM (p < 0.05 vs +/+) after CCI. Conclusion: An endogenous neuroprotectant role for iNOS-derived nitric oxide after TBI is strongly supported.
All Science Journal Classification (ASJC) codes
- Critical Care and Intensive Care Medicine