Neuroglia, Volume 6, Issue 3 (September 2025) – 6 articles

Hydrocephalus is a neurological disorder caused by cerebrospinal fluid (CSF) accumulation due to impaired production, circulation, or reabsorption from trauma, neurocysticercosis, neoplasms, subarachnoid hemorrhage, or genetic mutations. This review examines glial remodeling in the ventricular–subventricular zone (V-SVZ) and corpus callosum (CC) in response to hydrocephalus, as ventricular enlargement leads to structural alterations that impact cellular composition in the V-SVZ and CC of patients with hydrocephalus. Animal models of hydrocephalus indicate V-SVZ niche remodeling, ependymal thinning, reduced neuroblast proliferation, increased microglia and astrocytes, increased cell death, and enlarged extracellular matrix structures (fractones). Alterations in the corpus callosum encompass a reduction in width, abnormalities in myelin, astrogliosis, microglial reactivity, a decreased expression of myelin-related proteins (MOG and CNPase), and a reduced number of oligodendrocytes. Additionally, this narrative review highlights important cellular and molecular findings before and after CSF diversion surgery. This primary treatment restores the ventricular size but does not completely reverse glial changes, indicating that ongoing neuroinflammatory processes may interfere with neural recovery. Full article

Brain cancer is a heterogeneous collection of malignant neoplasms, such as glioblastoma multiforme (GBM), astrocytomas and medulloblastomas, with high morbidity and mortality. Its treatment is complicated by the tumor’s site, infiltrative growth mode and selective permeability of the blood–brain barrier (BBB). During tumor formation, the BBB dynamically remodels into the blood–brain tumor barrier (BBTB), disrupting homeostasis and preventing drug delivery. Furthermore, the TME (Tumor Micro Environment) supports drug resistance, immune evasion and treatment failure. This review points out the ways in which nanomedicine overcomes these obstacles with custom-designed delivery systems, sophisticated diagnostics and personalized therapies. Traditional treatments fail through a lack of BBB penetration, non-specific cytotoxicity and swift tumor adaptation. Nanomedicine provides greater drug solubility, protection against enzymatic degradation, target drug delivery and control over the release. Nanotheranostics’ confluence of therapeutic and diagnostic modalities allows for dynamic adjustment and real-time monitoring. Nanotechnology has paved the way for the initiation of a new era in precision neuro-oncology. Transcending the limitations of conventional therapy protocols, nanomedicine promises to deliver better outcomes by way of enhanced targeting, BBB penetration and real-time monitoring. Multidisciplinary collaboration, regulatory advancements and patient-centered therapy protocols customized to the individual patient’s tumor biology will be necessary to facilitate translation success in the future. Full article

Background: Astrocytes are not only structural cells but also play a pivotal role in neurogenesis and neuroprotection by secreting a variety of neurotrophic factors that support neuronal survival, growth, and repair. This study investigates the time-dependent responses of primary rat cortical astrocytes to oxygen–glucose deprivation (OGD) and evaluates the neuroprotective potential of astrocyte-conditioned medium (ACM). Methods: Primary rat cortical astrocytes and neurons were obtained from postnatal Sprague Dawley rat pups (P1–3) and embryos (E17–18), respectively. Astrocytes exposed to 6, 24, and 48 h of OGD (0.3% O₂) were assessed for viability, metabolic function, hypoxia-inducible factor 1 and its downstream genes expression. Results: While 6 h OGD upregulated protective genes such as Vegf, Glut1, and Pfkfb3 without cell loss, prolonged OGD, e.g., 24 or 48 h, led to significant astrocyte death and stress responses, including elevated LDH release, reduced mitochondrial activity, and increased expression of pro-apoptotic marker Bnip3. ACM from 6 h OGD-treated astrocytes significantly enhanced neuronal survival following 6 h OGD and 24 h reperfusion, preserving dendritic architecture, improving mitochondrial function, and reducing cell death. This protective effect was not observed with ACM from 24 h OGD astrocytes. Furthermore, 6 h OGD-ACM induced autophagy in neurons, as indicated by elevated LC3b-II and decreased p62 levels, suggesting autophagy as a key mechanism in ACM-mediated neuroprotection. Conclusions: These findings demonstrate that astrocytes exhibit adaptive, time-sensitive responses to ischemic stress and secrete soluble factors that can confer neuroprotection. This study highlights the therapeutic potential of targeting astrocyte-mediated signalling pathways to enhance neuronal survival following ischemic stroke. Full article

Epilepsy is one of the most prevalent chronic medical conditions that really can affect individuals at any age. A broader study of the pathogenesis of the epileptic condition will probably serve as the cornerstone for the development of new antiepileptic remedies that aim to treat epilepsy symptomatically as well as prevent the epileptogenesis process or regulate its progression. Cellular changes in the brain include oxidative stress, neuroinflammation, inflammatory cell invasion, angiogenesis, and extracellular matrix associated changes. The extensive molecular profiling of epileptogenic tissue has revealed details on the molecular pathways that might start and sustain cellular changes. In healthy brains, epilepsy develops because of vascular disruptions, such as blood–brain barrier permeability and pathologic angiogenesis. Key inflammatory mediators are elevated during epileptic seizures, increasing the risk of recurrent seizures and resulting in secondary brain injury. Prostaglandins and cytokines are well-known inflammatory mediators in the brain and, after seizures, their production is increased. These inflammatory mediators may serve as therapeutic targets in the clinical research of novel antiepileptic medications. The functions of inflammatory mediators in epileptogenesis are covered in this review. Oxidative stress also plays a significant role in the pathogenesis of various neurological disorders, specifically epilepsy. Antioxidant therapy seems to be crucial for treating epileptic patients, as it prevents neuronal death by scavenging excess free radicals formed during the epileptic condition. The significance of antioxidants in mitochondrial dysfunction prevention and the relationship between oxidative stress and inflammation in epileptic patients are the major sections covered in this review. Full article

Background: Elevated levels of methylmalonic acid (MMA) are observed in the bodily fluids and tissues of patients with methylmalonic aciduria, a metabolic disorder characterized by manifestations such as vomiting, lethargy, muscle weakness, seizures, and coma. Objectives and Methods: To better understand the neuropathological mechanisms underlying this condition, we investigated the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of MMA on antioxidant defenses, citric acid cycle functioning, and glial reactivity in the cerebral cortex and striatum of Wistar rats. Amino acid levels were also quantified. Results: i.p. and i.c.v. administration of MMA decreased reduced glutathione levels and altered the activities of different antioxidant enzymes in the cortex and striatum. The activity of the citric acid cycle enzyme succinate dehydrogenase was diminished in both brain regions by i.p. and i.c.v. administration. Citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase activities were further inhibited in the striatum. Furthermore, the i.p. administration increased glial fibrillary acidic protein (GFAP) and glucose transporter 1 (GLUT1) levels, whereas i.c.v. administration elevated GFAP and ionized calcium-binding adaptor molecule 1 (IBA1) levels in the striatum, suggesting glial activation. In contrast, no significant changes in glial markers were detected in the cortex. Moreover, synaptophysin levels remained unaltered in both regions. Finally, i.p. administration increased glutamate, glycine, and serine levels and reduced tyrosine concentrations in the striatum. Conclusions: Our findings indicate that oxidative stress, bioenergetic dysfunction, and glial reactivity induced by MMA may contribute to the neurological deficits observed in methylmalonic aciduria. Full article

Glial cells exhibit multifaceted functions and represent essential contributors to various physiological processes in the brain, rather than just being silent supportive cells to neurons. Different glial populations of the central nervous system within involved brain regions play various functions, express different proteins, and result in fluctuating effects when altered. Glial cell pathologies were detected in most mental disorders including suicidal behavior. Suicidal behavior represents a health problem of high importance worldwide, where protective measures are required to be taken at many levels. Studies on patients with mental disorders that represent risk factors for suicidal behavior revealed multiple changes in the glia at diverse levels, including variations regarding the expressed glial markers. This review summarizes the role of glia in some psychiatric disorders and highlights the crosslink between changes at the level of glial cells and development of suicidal behavior in patients with an underlying psychiatric condition; in addition, the interplay and interconnection between suicidal behavior and other mental diseases will shed light on the routes of personalized therapy involving the development of glia-related drugs. Full article