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- Volume 23, Issue 3, 2025
Current Neuropharmacology - Volume 23, Issue 3, 2025
Volume 23, Issue 3, 2025
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Pharmacological Strategies and Surgical Management of Posthemorrhagic Hydrocephalus Following Germinal Matrix-Intraventricular Hemorrhage in Preterm Infants
Authors: Zhao Yang, Tian Tian Luo, Ya-Lan Dai, Han-Xiao Duan, Cheong-Meng Chong and Jun TangGerminal matrix-intraventricular hemorrhage (GM-IVH) is a detrimental neurological complication that occurs in preterm infants, especially in babies born before 32 weeks of gestation and in those with a very low birth weight. GM-IVH is defined as a rupture of the immature and fragile capillaries located in the subependymal germinal matrix zone of the preterm infant brain, and it can lead to detrimental neurological sequelae such as posthemorrhagic hydrocephalus (PHH), cerebral palsy, and other cognitive impairments. PHH following GM-IVH is difficult to treat in the clinic, and no level-one strategies have been recommended to pediatric neurosurgeons. Several cellular and molecular mechanisms of PHH following GM-IVH have been studied in animal models, but no effective pharmacological strategies have been used in the clinic. Thus, a comprehensive understanding of molecular mechanisms, potential pharmacological strategies, and surgical management of PHH is urgently needed. The present review presents a synopsis of the pathogenesis, diagnosis, and cellular and molecular mechanisms of PHH following GM-IVH and explores pharmacological strategies and surgical management.
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Major Depression in Comorbidity with Substance use Disorders: Patients’ Features and Clinical-Neurobiological Rationale of Antidepressant Treatments
The frequent co-occurrence of major depressive disorder (MDD) and substance use disorders (SUDs) entails significant clinical challenges. Compared to patients with MDD alone, patients with MDD and SUD often show increased anhedonia, emotional blunting, and impaired cognitive function. These symptoms lead to an inability to control cravings, more substance use, increased relapse rates, and poor adherence to the treatment. This fosters a detrimental cycle leading to more severe depressive symptoms, functional impairment, and chronicity, culminating in heightened morbidity, mortality, and healthcare resource utilization. Data on antidepressant treatment of MDD-SUD patients are inconclusive and often conflicting because of a number of confounding factors in clinical trials or difficulty in dissecting the specific contributions of pharmacological versus psychological interventions in real-world studies. The patient's unique clinical features and specific SUD and MDD subtypes must be considered when choosing treatments. Ideally, drug treatment for MDD-SUD should act on both conditions and address core symptoms such as anhedonia, craving, and cognitive dysfunction while ensuring minimal emotional blunting, absence of drug interactions, and no addictive potential. This approach aims to address unmet needs and optimize the outcomes in a clinical population often underrepresented in treatment paradigms.
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Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment
Authors: Chalton Manengu, Chun-Hao Zhu, Guo-Dong Zhang, Miao-Miao Tian, Xiao-Bing Lan, Li-Jun Tao, Lin Ma, Yue Liu, Jian-Qiang Yu and Ning LiuNeuropathic pain, a multifaceted and incapacitating disorder, impacts a significant number of individuals globally. Despite thorough investigation, the development of efficacious remedies for neuropathic pain continues to be a formidable task. Recent research has revealed the potential of metabotropic glutamate receptor 5 (mGlu5) as a target for managing neuropathic pain. mGlu5 is a receptor present in the central nervous system that has a vital function in regulating synaptic transmission and the excitability of neurons. This article seeks to investigate the importance of mGlu5 in neuropathic pain pathways, analyze the pharmacological approach of targeting mGlu5 for neuropathic pain treatment, and review the negative allosteric mGlu5 modulators used to target mGlu5. By comprehending the role of mGlu5 in neuropathic pain, we can discover innovative treatment approaches to ease the distress endured by persons afflicted with this incapacitating ailment.
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A New Augmentation Strategy against Depression Combining SSRIs and the N-terminal Fragment of Galanin (1-15)
Depression is one of the most disabling mental disorders, with the second highest social burden; its prevalence has grown by more than 27% in recent years, affecting 246 million in 2021. Despite the wide range of antidepressants available, more than 50% of patients show treatment-resistant depression. In this review, we summarized the progress in developing a new augmentation strategy based on combining the N-terminal fragment of Galanin (1-15) and SSRI-type antidepressants in animal models.
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An Association of Framingham Risk Score with Patient Determined Disease Steps in a Cohort of Relapsing-Remitting Multiple Sclerosis Patients: An Italian Real-World Monocentric Experience
Authors: Aurora Zanghì, Paola Sofia Di Filippo, Carlo Avolio and Emanuele D’AmicoBackgroundThe associations between Multiple Sclerosis (MS) and cardiovascular diseases, drawn from epidemiological studies, have attracted much attention in recent years.
Materials and MethodsThe present study employed a monocentric, observational, retrospective cohort design. The primary objective of the study was to describe the Framingham Risk Score (FRS) rate in a cross-sectional analysis of our cohort of relapsing-remitting MS patients who are regularly followed up and, if applicable, to identify any association with the patient's Patient Determined Disease Steps (PDDS). Cardiovascular risk was classified as follows: low if the FRS is less than 10%, moderate if it is 10% to 19%, and high if it is 20% or higher.
ResultsA total cohort of 229 patients was enrolled. The sample consists of 163 women (71.2%). FRS categories were distributed as follows: 97 (42.3%) patients had low FRS, 84 (36.7%) patients had moderate FRS, and 48 (21%) patients had high FRS. In the univariable ordinal regression analysis, one one-point increase in the PDDS scale was associated with a 24% risk of high FRS (vs. low) (proportional odds ratio [OR]=2.426, 95% confidence interval [CI] 1.660-3.545; p <.0001). The results were also confirmed by the EDSS score, with a point increase in the EDSS score associated with a 19% risk of high FRS (vs. low) (proportional OR=1.953, 95% CI 1.429-2.669-1.04; p <.0001).
ConclusionThe FRS demonstrated an association with the patient's “perception of the disease” as indicated by the PDDS. Further studies with larger cohorts are needed to adequately address cardiovascular risk in life-threatening conditions, such as MS.
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Appraisal of the Neuroprotective Potentials of Isoeugenol Using In-vitro, In-vivo and In-silico Approaches
Authors: Bandar A. Alyami, Zeeshan Ahmad, Mehreen Ghufran, Mater H. Mahnashi, Abdul Sadiq and Muhammad AyazBackgroundAlzheimer's disease (AD) is a neurodegenerative condition that affects the elder population and is linked to behavioral instability and cognitive decline. Only a few drugs are approved for clinical management of AD. Volatile oils and their components exhibit diverse pharmacological potentials, including neuroprotective properties. The current study aimed to evaluate isoeugenol's neuroprotective potentials against cognitive impairments caused by scopolamine.
MethodsStandard protocols were followed in the in-vitro antioxidant, cholinesterase inhibitory and molecular docking assays. Isoeugenol was initially evaluated for antioxidant potential using DPPH and ABTS free radicals scavenging assays. Subsequently, AChE/BChE inhibition studies were performed following Ellman’s assay. To assess the compound's binding effectiveness at the enzymes' target site, it was docked against the binding sites of cholinesterase. The effect of isoeugenol supplementation on scopolamine-induced amnesia was assessed using Shallow Water Maze (SWM), Y-Maze and Elevated Plus Maze (EPM) tests.
ResultsIn DPPH and ABTS assays, isoeugenol exhibited considerable efficacy against free radicals with IC50 of 38.97 and 43.76 μg/mL, respectively. Isoeugenol revealed 78.39 ± 0.40% and 67.73 ± 0.03% inhibitions against AChE and BChE, respectively, at 1 mg/ml concentration. In docking studies, isoeugenol exhibited a docking score of -12.2390, forming two hydrogen bonds at the active site residues of AChE. Further, with a docking score of -10.1632, isoeugenol binds adequately to the BChE enzyme via two arene-hydrogen interactions and one hydrogen bond.
ConclusionIsoeugenol offered considerable protection against scopolamine-induced memory deficits and improved the special memory of the rodents.
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Dietary Intervention with Omega-3 Fatty Acids Mitigates Maternal High-Fat Diet-Induced Behavioral and Myelin-Related Alterations in Adult Offspring
BackgroundMaternal high-fat diet (HFD) during pregnancy and lactation induces depression-like phenotype and provokes myelin-related changes in rat offspring in the prefrontal cortex (PFCTX), which persist even to adulthood.
ObjectiveDue to the plasticity of the developing brain, it was decided to analyze whether depression-like phenotype and myelin-related changes in the early lifetime induced by maternal HFD (60% energy from fat) could be reversed by the omega-3 fatty acid-enriched diet (Ω3D) given from the post-weaning period until adulthood (63rd day of life) in offspring.
MethodsWe analyzed the effect of post-weaning Ω3D on the depressive-like phenotype (assessed by the forced swimming test) and myelin-related changes (measured using RT-qPCR, ELISA, and immunofluorescence staining) in the PFCTX of adult offspring.
ResultsΩ3D reversed increased immobility time in adult offspring induced by maternal HFD, without affecting the animals' locomotor activity. Molecularly, Ω3D normalized the reduced expression levels of myelin-oligodendrocyte glycoprotein (MOG), as well as myelin and lymphocyte protein (MAL) in males and MOG in females in the PFCTX, changes initially induced by maternal HFD. Additionally, Ω3D normalized the quantity of oligodendrocyte precursor cells and mature oligodendrocytes in the prelimbic, infralimbic, and cingulate cortex in males, which were reduced following maternal HFD exposure. In females, the Ω3D effect was less pronounced, with normalization of oligodendrocyte precursors occurring only in the infralimbic cortex.
ConclusionThese findings suggest that Ω3D may play a significant role in correcting behavioral and neurobiological changes caused by adverse prenatal conditions.
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Early Enteral Feeding Restores Neurofilament Light Chain Serum Levels in Preterm Newborns
BackgroundPositive effects of early nutritional strategies on neurological outcomes have been observed when nutrients were administered by the enteral route, especially during the first week of life. Evidence reports that serum neurofilament light chain (NfL), a structural protein of neurons, is a specific and reliable biomarker of neuronal damage.
ObjectiveThe present study aimed to investigate the effect of early enteral nutrition (EN) in minimizing neuroaxonal damage and assessing NfL serum levels in preterm neonates.
MethodsFifty-four preterm neonates without severe brain impairment and 20 full-term babies as controls were enrolled from the Neonatal Intensive Care Unit at the Policlinico Umberto I in Rome. We performed blood sampling at birth (day of life 0 - DoL 0) in 20 full-term newborns and in 19 pre-term infants. Furthermore, we executed blood sampling at DoL 28 in other 22 pre-term newborns who received early enteral nutrition (EN) within the third DoL (Early-EN) and in 13 other pre-term newborns who received EN after the third DoL (Late-EN).
ResultsSerum levels of NfL were higher in preterm babies when compared to full-term neonates, at DoL 0 (48.81 ± 9.4 vs. 11.67 ± 1.4 pg/ml; p = 0.007). Interestingly, at DoL 28, serum NfL was significantly decreased in the Early-EN newborns compared to the Late-EN groups (15.22 ± 2.0 vs. 50.05 ± 17.9 pg/ml; p = 0.03).
ConclusionIt was shown that early enteral feeding, within the first week of life, could be a useful tool for limiting neurological impairment in pre-term neonates by restoring NfL.
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Volumes & issues
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Volume 23 (2025)
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Volume 22 (2024)
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Volume 21 (2023)
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Volume 20 (2022)
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Volume 19 (2021)
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Volume 18 (2020)
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Volume 17 (2019)
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Volume 16 (2018)
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Volume 15 (2017)
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Volume 14 (2016)
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Volume 13 (2015)
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Volume 12 (2014)
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Volume 11 (2013)
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Volume 10 (2012)
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Volume 9 (2011)
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Volume 8 (2010)
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Volume 7 (2009)
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Volume 6 (2008)
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Volume 5 (2007)
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Volume 4 (2006)
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Volume 3 (2005)
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Volume 2 (2004)
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Volume 1 (2003)