Effect of stroke on arginase expression and localization in the rat brain

Abstract

Because arginase and nitric oxide (NO) synthases (NOS) compete to degrade l-arginine, arginase plays a crucial role in the modulation of NO production. Moreover, the arginase 1 isoform is a marker of M2 phenotype macrophages that play a key role in tissue remodeling and resolution of inflammation. While NO has been extensively investigated in ischemic stroke, the effect of stroke on the arginase pathway is unknown. The present study focuses on arginase expression/activity and localization before and after (1, 8, 15 and 30 days) the photothrombotic ischemic stroke model. This model results in a cortical lesion that reaches maximal volume at day 1 post-stroke and then decreases as a result of astrocytic scar formation. Before stroke, arginase 1 and 2 expressions were restricted to neurons. Stroke resulted in up-regulation of arginase 1 and increased arginase activity in the region centered on the lesion where inflammatory cells are present. These changes were associated with an early and long-lasting arginase 1 up-regulation in activated macrophages and astrocytes and a delayed arginase 1 down-regulation in neurons at the vicinity of the lesion. A linear positive correlation was observed between expressions of arginase 1 and glial fibrillary acidic protein as a marker of activated astrocytes. Moreover, the pattern of arginase 1 and brain-derived neurotrophic factor (BDNF) expressions in activated astrocytes was similar. Unlike arginase 1, arginase 2 expression was not changed by stroke. In conclusion, increased arginase 1 expression is not restricted to macrophages in inflammation elicited by stroke but also occurs in activated astrocytes where it may contribute to neuroplasticity through the control of BDNF production.

Inhibition of MyD88 Signaling Skews Microglia/Macrophage Polarization and Attenuates Neuronal Apoptosis in the Hippocampus After Status Epilepticus in Mice

“…However, our IHC experiments showed that ARG-1 was expressed mainly in astrocytes rather than in MG/MΦ during this period. ARG-1-expressing astrocytes were found previously in an ischemia model as well as in an autoimmune encephalomyelitis model [43,44], suggesting that ARG-1 in astrocytes may be a reactive response to pathological conditions.…”

“…NMDA receptors play critical roles in epileptic excitotoxicity, and NMDA receptor antagonists have been used to treat refractory seizures [49,50]. NMDA receptor subunit composition has been reported to be altered in epilepsy models [6,[41][42][43][44][45][46][47][48][49][50][51][52][53]. In addition, it has been reported that iNOS acts on mature neurons indirectly, increasing NMDA receptor expression [54].…”

Influence of Statin Pretreatment on Initial Neurological Severity and Short-Term Functional Outcome in Acute Ischemic Stroke Patients: The Fukuoka Stroke Registry

“…Pre-stroke statin treatment also appeared to show a more favorable effect on initial neurological severity in patients with first-ever stroke than in those with recurrent stroke. Experimental study has shown that expression and activity of arginase were increased after ischemic stroke [30]. Upregulation of arginase could inhibit NO production by competing with endothelial NO synthase (eNOS) for L -arginine as a common substrate, resulting in endothelial dysfunction and in blunted vasodilatory responses to endothelium-dependent vasodilating stimuli [31].…”

The Role of Nitric Oxide and Nitrosative Stress in Schizophrenia

“…A great number of studies in the literature suggest that there is a competition between arginase (amidinohydrolase, EC 3.5.3.1) and NOS and that they control each other's level (Quirié et al 2013 ). Because arginase and NOS compete for L -arginine, arginase plays a crucial role in the modulation of NO production.…”

“…Recently, Quirié et al reported that changes in arginase expression were not restricted to infl ammatory cells but also affected activated astrocytes and neurons. Evidence of a similar pattern of arginase 1 and brain-derived neurotrophic factor expression in astrocytes opens new possibilities for a potential link between arginase and neuroplasticity (Quirié et al 2013 ).…”