Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation

Role of nitric oxide (NO) in inflammationary diseases such as multiple sclerosis (MS) has been proposed previously. We sought to examine if NO plays centrally a key role in MS related phenomena; demyelination or neuroinflammation. Female Wistar rats (weighing 200–250 g) were mounted in a stereotaxic apparatus and received injections of l-arginine aimed at corpus callosum (AP: 1.2, L: ± 1.8, V: 3.2). The drug (50–200 μg/rat) was microinjected intra-corpus callosum repeatedly (3–5 times/each per day). Control groups solely received saline (1 μg/rat) into the corpus callosum. The animals were tested for the novelty seeking behavior using the conditioning task. Memory impairment was examined using the shuttle box and Y-maze. l-NAME was pre-injected to l-arginine to involve the NO. All animals' brains were also processed for histological evaluation. l-arginine produced significant changes in the novelty seeking behavior but not in the memory formation, evidenced by passive avoidance and alternation behaviors. Pre-injection of l-NAME reversed the response to l-arginine. Present study further revealed a prominent inflammation as well as myelin elimination in the l-arginine treated rats' brains. These data suggest that the NO infusion in the myelin rich areas such as corpus callosum may lead to MS signs centrally.

Research highlights
► Role of NO in neuroinflammatory diseases e.g MS was shown.
► It has been overproduced centrally in Corpus Callosum.
► This cause myelin reduction, inflammation and cognition defect.