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.

Background: Atrial fibrillation is a major health problem due to the stroke risk associated with it. To reduce stroke risk, oral anticoagulants (OAC) are prescribed using the CHA2DS2-VASc (Congestive heart failure; Hypertension; Age ≥75 years; Diabetes Mellitus; Stroke; Vascular disease; Age 65–74 years; Sex category) risk score, a clinical probability assessment that includes a combination of risk factors predicting the probability of a stroke. Not all patients with high risk are receiving this treatment. The aim of this study was to assess physician adherence to clinical guidelines concerning the OAC treatment and to identify the factors that were associated with the decision to prescribe it. Methods: Registry data from 784 patients with non-valvular atrial fibrillation were evaluated in this retrospective cross-sectional study. Demographic data, subtype of AF, comorbidities associated with higher stroke and bleeding risk, and antithrombotic treatment received were recorded. We compared stroke and bleeding risk in patients with and without OAC treatment to determine if the clinicians followed guidelines: prescribed when necessary and abstained when not needed. Results: OAC treatment was administered in 617 (78.7%) patients. Of the 167 patients who did not receive OAC, 161 (96.4%) were undertreated according to their risk score, as opposed to those who received OAC in which the percentage of overtreated was 3.2%. Most undertreated patients (60.5%, p < 0.001) were with paroxysmal atrial fibrillation subtype. Conclusions: The decision to use anticoagulants for stroke prevention was based on the type of atrial fibrillation, rather than on the risk of stroke as quantified by CHA2DS2-VASc as per the recommended guidelines.

Background and objectives: The cochlear implant is not only meant to restore auditory function, but it also has a series of benefits on the psychomotor development and on the maturation of central auditory pathways. In this study, with the help of neuropsychological tests and cortical auditory potentials (CAEPs), we intend to identify a series of instruments that allow us to monitor children with a cochlear implant, and later on, to admit them into an individualized rehabilitation program. Materials and methods: This is a longitudinal study containing 17 subjects (6 boys and 11 girls) diagnosed with congenital sensorineural hearing loss. The average age for cochlear implantation in our cohort is 22 months old. Each child was tested before the cochlear implantation, tested again 3 months after the implant, and then 6 months after the implant. To test the general development, we used the Denver Developmental Screening Test (DDST II). CAEPs were recorded to assess the maturation of central auditory pathways. Results: The results showed there was progress in both general development and language development, with a significant statistical difference between the overall DQ (developmental quotient) and language DQ before the cochlear implantation and three and six months later, respectively. Similarly, CAEP measurements revealed a decrease of positive-going component (P1) latency after cochlear implantation. Conclusion: CAEPs and neuropsychological tests prove to be useful instruments for monitoring the progress in patients with cochlear implants during the rehabilitation process.

Introduction: Atherosclerosis represents the process by which fibrous plaques are formed in the arterial wall, increasing its rigidity with a subsequent decrease in blood flow which can lead to several cardiovascular events. Seeing as vitamin K antagonists are involved in the pathogenesis of atherosclerosis, we decided to investigate whether polymorphisms in genes that influence vitamin K metabolism might have an impact in modulating the risk of plaque formation. Patients and Methods: In the current study we included adult patients admitted in the Clinical Municipal Hospital of Cluj-Napoca without any carotid or femoral plaques clinically visible at the initial investigation, and a five year follow-up was subsequently performed. We recorded the following patient characteristics: age at inclusion, gender, area of living, smoking, presence of carotid and/or femoral plaques at five years, ischemic heart disease, arterial hypertension, atrial fibrillation, heart failure, diabetes mellitus, obesity, dyslipidemia, drug (oral anticoagulants, antihypertensives, hypolipidemic, anti-diabetic) use and status for the following gene polymorphisms: VKORC1 1639 G>A, CYP4F2 1347 G>T and GGCX 12970 C>G. Results: We observed that the major predictor of both carotid and femoral plaque formation is represented by ischemic cardiac disease. VKORC1 and CYP4F2 polymorphisms did not predict plaque formation, except for VKORC1 homozygous mutants. Nonetheless, both VKORC1 and CYP4F2 interacted with ischemic cardiac disease, increasing the risk of developing a carotid plaque, while only CYP4F2, but not VKORC1, interacted with ischemic cardiac disease to increase the risk of femoral plaque formation. Conclusions: We documented that CYP4F2 and VKORC1 polymorphisms boost the proinflammatory plaque environment (observed indirectly through the presence of ischemic heart disease), increasing the risk of plaque development.

Glatiramer acetate (GA) is one of the most widely used disease-modifying drugs for the treatment of relapsing-remitting multiple sclerosis; is assumed to have inductor effects on neurotrophic factor expression. One of these neurotrophic factor systems is the brain-derived neurotrophic factor (BDNF)/receptor tyrosine kinase B (TrkB) pathway. Peripheral blood is thought to contain soluble BDNF, and some blood cells express TrkB. We attempted to determine whether GA treatment leads to changes in plasma BDNF levels and TrkB activation. Such a phenomenon are relapsing-remitting multiple sclerosis patients is significantly reduced; GA treatment is not influencing peripheral BDNF levels, after one year of sustained therapy, not from the point of view of total free BDNF nor the phosphorylated TrkB.

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