Administration of S-methyl-l-thiocitrulline protects against brain injuries after intracerebral hemorrhage

• Administering SMTC decreased the activity of NADH-d in the ICH brain.
• SMTC treatment reduced activation of gelatinolytic enzymes after ICH.
• SMTC decreased the loss of laminin- and occludin-stained vessels in the ICH brain.
• SMTC treatment reduced neuronal death in the perihematomal region.
• The administration of SMTC improved neurological deficits after ICH.

Although intracerebral hemorrhage (ICH) increases the level of glutamate in the perihematomal area and cerebral spinal fluid (CSF) in the ICH acute phase, it is unclear whether elevated glutamate activates neuronal nitric oxide synthase (nNOS) in the ICH brain and whether nNOS is an important target for ICH treatment. Here, we assessed the role of the nNOS inhibitor S-methyl-l-thiocitrulline (SMTC) in the activity of NADPH-d and ICH-induced brain injuries. An autologous blood intracerebral infusion model in male rats was used. All of the rats were sacrificed 24 h after ICH. ICH increased NADPH-d activity in the striatum. Administering SMTC 3 h after ICH decreased the activity of NADH-d (p < 0.05 vs. the ICH group). The activation of gelatinolytic enzymes in the perihematomal region of the striatum was reduced by SMTC treatment (p < 0.01, vs. the ICH group). The loss of laminin- and occludin-stained vessels was significant in perihematomal regions after 24 h of ICH and was significantly attenuated by the administration of SMTC (p < 0.01 for laminin, p < 0.05 for occluding, compared with the ICH group). Neuronal death and neurological deficits after ICH were also decreased in SMTC treatment rats (p < 0.01, vs. the ICH group). The results suggest that the administration of the nNOS inhibitor SMTC after ICH protects against ICH-induced brain injuries and improves neurological function.