Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of human multiple sclerosis (MS). We have evaluated the role of oxidative and nitrosative stress, as the causal factors in the development of EAE, responsible for the damage of cardinal cellular components, such as lipids, proteins and nucleic acids, resulting in demyelination, axonal damage, and neuronal death. EAE was induced in female Sprague-Dawley rats, 3 months old (300±20 g), by immunization with myelin basic protein in combination with Complete Freund's adjuvant (CFA). The animals were divided into seven groups: control, EAE, CFA, EAE+aminoguanidine (AG), AG, EAE+N-acetyl-L-cysteine (NAC) and NAC. The animals were sacrificed 15 days after EAE induction, and the levels of nitrosative and oxidative stress were determined in 10% homogenate of the whole encephalitic mass. In EAE rats, brain NO production and MDA level were significantly increased (P<0.001) compared to the control values, whereas AG and NAC treatment decreased both parameters in EAE rats compared to EAE group (P<0.001). Glutathione (GSH) was reduced (P<0.001) in EAE rats in comparison with the control and CFA groups, but increased in EAE+AG and EAE+NAC group compared to the EAE group (P<0.01). Superoxide dismutase (SOD) activity was significantly decreased (P<0.001) in the EAE group compared to all other experimental groups. The clinical expression of EAE was significantly decreased (P<0.05) in the EAE groups treated with AG and NAC compared to EAE rats, during disease development. The obtained results prove an important role of oxidative and nitrosative stress in the pathogenesis of EAE, whereas AG and NAC protective effects offer new possibilities for a modified combined approach in MS therapy.

Purpose of review: Medication-overuse headache (MOH) is an important problem worldwide, with different areas of controversy regarding its entity. This article reviews the risk factors, comorbidities, pathophysiology, clinical presentation, effective management, and prognosis of MOH by summarizing and integrating the results and findings from previously performed more than 15,000 studies (from 2010 to 2023) available from the scientific database of the University Medical Library in the University Clinical Center of Niš, which aimed to investigate and define the complexity of this type of headache. Recent finding: It has been proposed that all acute migraine medications can lead to MOH, with differences in the propensity of different agents to cause the problem. Early data suggests that triptans and other painkillers used for the acute treatment of migraine may be an exception. Recent studies show that practitioners and the general public are still largely unaware of the problem of medication overuse and its damaging effects. Summary: Although it is likely that MOH does occur, restricting the number of acute medications is necessary to prevent it. It is also possible that increasing amounts of acute medications are simply a reflection of poorly controlled headaches rather than a cause. Further research needs to be developed to identify more precise mechanisms for effective MOH management and its evolution.