Aquaporin-4 (AQP4) is the most abundant water channel in the brain, and its inhibition before inducing focal ischemia, using the AQP4 inhibitor TGN-020, has been showed to reduce oedema in imaging studies. Here, we aimed to evaluate, for the first time, the histopathological effects of a single dose of TGN-020 administered after the occlusion of the medial cerebral artery (MCAO). On a rat model of non-reperfusion ischemia, we have assessed vascular densities, albumin extravasation, gliosis, and apoptosis at 3 and 7 days after MCAO. TGN-020 significantly reduced oedema, glial scar, albumin effusion, and apoptosis, at both 3 and 7 days after MCAO. The area of GFAP-positive gliotic rim decreased, and 3D fractal analysis of astrocytic processes revealed a less complex architecture, possibly indicating water accumulating in the cytoplasm. Evaluation of the blood vessels revealed thicker basement membranes colocalizing with exudated albumin in the treated animals, suggesting that inhibition of AQP4 blocks fluid flow towards the parenchyma in the paravascular drainage pathways of the interstitial fluid. These findings suggest that a single dose of an AQP4 inhibitor can reduce brain oedema, even if administered after the onset of ischemia, and AQP4 agonists/antagonists might be effective modulators of the paravascular drainage flow.

Seric biomarkers have been tested in a large number of studies on traumatic brain injuries (TBI) patients in order to predict severity, especially related to the short-term outcome. However, TBI patients have a high risk of developing long-term complications such as physical disability, cognitive impairment, psychiatric pathology, epilepsy, and others. The aim of this study was to assess the correlation between protein biomarkers S100 and neuron-specific enolase (NSE) and neurocognitive status at 10- and 90-days post-injury. Both biomarkers were tested in the first 4h and after 72h post-injury in 62 patients with moderate-severe TBI. The patients were evaluated by a series of neurocognitive tests: Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale-Extended (GOSE), The Mini-Mental State Examination (MMSE), Processing Speed Index (PSI), and Stroop Test, at 10 and 90 days post-injury and supplementary by the Hospital Anxiety and Depression Scale at 90 days. For evaluating the whole neurocognitive status instead of every scale separately, we used Structural Equation Modeling (SEM), while for anxiety and depressive symptoms, we used multiple regression analyses. SEM showed that NSE values at 4 hours were significant predictors of the cognitive status at 10 (p=0.034) and 90 days (p= 0.023). Also, there were found significant correlations between NSE at 4h and the anxiety level. This study demonstrated a significant correlation between NSE at 4h and short and medium-term neuropsychological outcomes, which recommends using this biomarker for selecting patients with a higher risk of cognitive dysfunction.

Stroke is still a significant health problem that affects millions of people worldwide, as it is the second-leading cause of death and the third-leading cause of disability. Many changes have occurred in the treatment of acute ischemic stroke. Although the innovative concepts of neuroprotection and neurorecovery have been vigorously investigated in a substantial number of clinical studies in the past, only a few trials managed to increase the number of promising outcomes with regard to the multidimensional construct of brain protection and rehabilitation. In terms of pharmacological therapies with proven benefits in the post-ischemic process, drugs with neurorestorative properties are thought to be effective in both the acute and chronic phases of stroke. One significant example is Cerebrolysin, a combination of amino acids and peptides that mimic the biological functions of neurotrophic factors, which has been shown to improve outcomes after ischemic stroke, while preserving a promising safety profile. The purpose of this paper is to offer an overview on the role and impact of Cerebrolysin for ischemic stroke care, by touching on various aspects, from its complex, multimodal and pleiotropic mechanism of action, to its efficacy and safety, as well as cost effectiveness.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), affecting mostly young-aged people. As a chronic incurable disease, in most cases, it can lead to progressive neurological impairment and severe disability. Depression and anxiety are major distress factors for MS patients, being considerably aggravating elements for their functional capacity. In this study, we analysed the mood disorder distribution and the possible correlations between depression, anxiety, automatic negative thoughts, and MS disability. We took into consideration 146 MS patients, who completed a series of questionnaires: Beck Depression Inventory II (BDI-II), Endler Multidimensional Anxiety Scales-State (EMAS-S), and Automatic Thoughts Questionnaire (ATQ). The Expanded Disability Status Scale (EDSS) was used to measure the neurological disability. Of all patients, 30.1% had symptoms for depression and 11% presented suicidal thoughts. After analysing the correlation index between each variable, we found that there is a mild positive correlation between depression and the EDSS score and between anxiety and the EDSS score. A difference is found in the test scores according to the type of the MS disease. Also, automatic negative thoughts are strongly correlated with depression and anxiety, but do not mediate the path between psychological comorbidities and neurological impairment. Sociodemographic features and interferon-beta treatment were not related to the intensity of the mood disorders. The study suggests that depression and anxiety are frequently encountered among MS patients and these mental disfunctions have an impact on their disability. A proper identification of these risk factors may improve the quality of life for these patients.