Astrocytes play an important role in neuroinflammation by producing proinflammatory molecules. In response to various stressful stimuli, astrocytes can become senescent or reactive, both are present in age-associated cognitive impairment and other neurodegenerative diseases, and contribute to neuroinflammation. However, there are no studies that compare the cytokines secreted by these types of astrocytes in the brain during aging. Hence, we aimed to broaden the picture of the secretory profiles and to differentiate the variability between them. Therefore, a systematic review was conducted following the guidelines of the \"Reporting Items for Systematic Review and Meta-Analyses\". Only three studies that met the inclusion terms evaluated age-related cytokine secretion, however, no evaluation of senescence or gliosis was performed. Consequently, to increase the spectrum of the review, studies where those phenotypes were induced and cytokines determined were included. Although some cytokines were common for gliosis and senescence, some interesting differences were also found. The dissimilarities in cytokines secretion between these phenotypes could be studied in the future as potential markers.

Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and disease. Enteric glia react to intestinal inflammation by converting to a \'reactive glial phenotype\' and enteric gliosis, contributing to neuroinflammation, enteric neuropathy, bowel motor dysfunction and dysmotility, diarrhea or constipation, \'leaky gut\', and visceral pain. The focus of the minireview is on the impact of inflammation on enteric glia reactivity in response to diverse insults such as intestinal surgery, ischemia, infections (C. difficile infection, HIV-Tat-induced diarrhea, endotoxemia and paralytic ileus), GI diseases (inflammatory bowel diseases, diverticular disease, necrotizing enterocolitis, colorectal cancer) and functional GI disorders (postoperative ileus, chronic intestinal pseudo-obstruction, constipation, irritable bowel syndrome). Significant progress has been made in recent years on molecular pathogenic mechanisms of glial reactivity and enteric gliosis, resulting in enteric neuropathy, disruption of motility, diarrhea, visceral hypersensitivity and abdominal pain. There is a growing number of glial molecular targets with therapeutic implications that includes receptors for interleukin-1 (IL-1R), purines (P2X2R, A2BR), PPARα, lysophosphatidic acid (LPAR1), Toll-like receptor 4 (TLR4R), estrogen-β receptor (ERβ) adrenergic α-2 (α-2R) and endothelin B (ETBR), connexin-43 / Colony-stimulating factor 1 signaling (Cx43/CSF1) and the S100β/RAGE signaling pathway. These exciting new developments are the subject of the minireview. Some of the findings in pre-clinical models may be translatable to humans, raising the possibility of designing future clinical trials to test therapeutic application(s). Overall, research on enteric glia has resulted in significant advances in our understanding of GI pathophysiology.

Hydrogels have been used as promising biomaterials for regeneration and control of pathophysiological events after traumatic spinal cord injuries (TSCI). However, no systematic comparison was conducted to show the effect of hydrogels on pathophysiological events. This study was designed to address this issue and evaluate the regenerative potential of hydrogels after TSCI. From 2857 records found in MEDLINE and EMBASE databases (April 23, 2021), 49 articles were included based on our inclusion/exclusion criteria. All studies discussing the effect of hydrogels on at least one of the main pathophysiological events after TSCI, including inflammation, axon growth, remyelination, glial scar formation, cavity size, and locomotor functional recovery were included. For statistical analysis, we used mean difference with 95% confidence intervals for locomotor functional recovery. The results showed that both natural and synthetic hydrogels could reduce the inflammatory response, hinder glial scar formation, and promote axon growth and vascularization. Also, the meta-analysis of the BBB score showed that using the hydrogels can lead to locomotor functional recovery. It was found that hydrogels are more efficient when used in transection and hemisection injuries (SMD: 1.89; 95% CI: 1.26, 2.52; P < .00001) compared to other injury models. The pre-formed implanted hydrogels (SMD: 1.79; 95% CI: 1.24, 2.34; P < .00001) found to be more effective compared to injection (SMD: 1.58; 95% CI: 0.64, 2.52; P = 0.0009). In conclusion, based on the available evidence, it was concluded that hydrogel composition as well as implantation method are dominant factors affecting tissue regeneration after TSCI and should be chosen according to the injury model in animal studies.

Astrocytes regulate synaptic communication and are essential for proper brain functioning. In Alzheimer\'s disease (AD) astrocytes become reactive, which is characterized by an increased expression of intermediate filament proteins and cellular hypertrophy. Reactive astrocytes are found in close association with amyloid-beta (Aβ) deposits. Synaptic communication and neuronal network function could be directly modulated by reactive astrocytes, potentially contributing to cognitive decline in AD. In this review, we focus on reactive astrocytes as treatment targets in AD in the APPswePS1dE9 AD mouse model, a widely used model to study amyloidosis and gliosis. We first give an overview of the model; that is, how it was generated, which cells express the transgenes, and the effect of its genetic background on Aβ pathology. Subsequently, to determine whether modifying reactive astrocytes in AD could influence pathogenesis and cognition, we review studies using this mouse model in which interventions were directly targeted at reactive astrocytes or had an indirect effect on reactive astrocytes. Overall, studies specifically targeting astrocytes to reduce astrogliosis showed beneficial effects on cognition, which indicates that targeting astrocytes should be included in developing novel therapies for AD.

Sudden Unexpected Death in Childhood (SUDC) is the unexplained death of children aged between 1 and 18 years old. Hippocampal abnormalities have previously been described in Sudden Unexpected Death in Epilepsy (SUDEP) and it is possible that SUDC shares similar pathogenic mechanisms with SUDEP. Our aim was to determine the prevalence of hippocampal abnormalities, history of seizures and demographic features in our caseload of SUDC, SUDEP and SIDS cases. A review of post-mortem reports from 2003 to 2018 was carried out to identify cases of SUDC, SUDEP and SIDS. Histological evidence of hippocampal abnormalities, patient demographics (age, gender), sleeping position, and past medical history (history of seizures and illness 72 hours prior to death) were recorded. Statistical analysis was performed to compare the three groups. 48 SUDC, 18 SUDEP and 358 SIDS cases were identified. Hippocampal abnormalities associated with temporal lobe epilepsy were found in 44.4% of SUDC cases. 5/15 SUDC cases with a history of seizures demonstrated hippocampal abnormalities. SUDC cases were also more likely to be found prone compared to SIDS cases. In comparison with SIDS, both SUDC and SUDEP cases were more likely to demonstrate hippocampal abnormalities (SUDC: (OR = 9.4, 95% CI: 3.1-29.1, p < 0.001; SUDEP: OR = 35.4, 95% CI: 8.3-151.5, p < 0.001). We found a potential link between hippocampal abnormalities and epileptic seizures in SUDC. A concerted effort should be directed towards consistent sampling and standardized description of the hippocampus and clinical correlation with a history of seizures/epilepsy in postmortem reports.

Acute bacterial meningitis in infants and newborns represents a medical emergency and a significant cause of mortality and morbidity worldwide. Moraxella catarrhalis has been considered a microorganism with low pathogenic potential, and only in exceptional cases has it been found to cause meningitis in infants and immunocompetent people. We will now document an unusual case of an unexpected and sudden death of a 40-day-old infant due to acute meningitis from M. catarrhalis, apparently asymptomatic and subsequently diagnosed by an autopsy. According to our knowledge this is the first case of unexpected infant death due to undiagnosed M. catarrhalis meningitis.The suggested case, as well as for the rarity of such a fatal event, should be considered a caution to pediatrics and neonatologists for M. catarrhalis can cause paucisymptomatic meningoencephalitis in infants which can be potentially fatal.From a forensic point of view, an autopsy accompanied by a multidisciplinary assessment is always necessary in cases of unexpected infant deaths to identify the causes.

Hydrocephalus is a rare and devastating complication of mumps encephalitis. The histopathological correlates of mumps infection in central nervous system tissues are not well-characterized. We present the case of a 54-year-old patient who suffered long-term neuropsychiatric sequelae and hydrocephalus as a consequence of a childhood mumps infection. Brain autopsy revealed significant dilation of the lateral and third ventricles. Aqueductal stenosis was not observed on premortem imaging or on gross examination. Histology revealed loss of ependymal epithelium throughout the aqueduct and ventricular system. Macrophage conglomerates were identified within the cerebral aqueduct at the level of the pons in addition to subjacent periaqueductal gliosis and scattered Rosenthal fibers. Together, these findings support primary ependymal injury as a pathophysiological mechanism in the development of chronic hydrocephalus following mumps infection. Finally, we review the existing literature and discuss potential mechanisms of disease.

This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.

Intraocular pressure (IOP) is a critical risk factor in glaucoma, and the available evidence derived from experimental studies in primates and rodents strongly indicates that the site of IOP-induced axonal damage in glaucoma is at the optic nerve head (ONH). However, the mechanisms that cause IOP-induced damage at the ONH are far from understood. A possible sequence of events could originate with IOP-induced stress in the ONH connective tissue elements (peripapillary sclera, scleral canal and lamina cribrosa) that leads to an increase in biomechanical strain. In consequence, molecular signaling cascades might be activated that result in extracellular matrix turnover of the peripapillary sclera, changing its biomechanical properties. Peripapillary sclera strain might induce reactive changes in ONH astrocytes and cause astrogliosis. The biological changes that are associated with ONH astrocyte reactivity could lead to withdrawal of trophic or metabolic support for optic nerve axons and cause their degeneration. Alternatively, the expression of neurotoxic molecules might be induced. Unfortunately, direct experimental in vivo evidence for these or other scenarios is currently lacking. The pathogenic processes that cause axonal degeneration at the ONH in glaucoma need to be identified before any regenerative therapy is likely to succeed. Several topics and emerging techniques should be pursued to enhance our understanding of the mechanisms that are behind axonal degeneration. Among them are: Advanced imaging techniques, the development of in vivo markers to identify axonal injury, the generation of molecular approaches for in vivo detection of mechanosensitivity and for molecular manipulation of the ONH, a more complete characterization of retinal ganglion cells, the use of organ cultures, 3D-bioprinting, and the engineering of microdevices that can measure pressure. Questions that need to be answered relate to the specific roles of astrogliosis, neuroinflammation, blood flow and intracranial pressure in axonal degeneration at the ONH.

Malformations of cortical development (MCDs), such as cortical dysplasia and tuberous sclerosis complex, are common causes of intractable epilepsy, especially in paediatric patients. Recently, mounting evidence points to a common pathology of these disorders. Hyperactivation of mammalian target of rapamycin (mTOR) has been proposed as a central mechanism in most, if not all, MCDs. The transition from mTOR hyperactivation and cellular abnormalities to large-scale functional changes and seizure is, however, not fully understood. In this article we set out to review currently available information regarding MCD pathology, focusing on glial cells - especially astrocytes - and their interactions with the brain vascular system. A large body of evidence points to these elements as potential targets in MCD. Here, we attempt to provide a review of this evidence and propose some hypotheses regarding the possible chain of events linking primary glial dysfunction and epilepsy. We focus on extracellular matrix remodelling, blood-brain barrier leakage and failure of astrocyte-dependent removal of extracellular debris. We posit that the failure of these systems results in a chronically pro-inflammatory environment, maintaining local astrocytes in a state of gliosis, with increased susceptibility to seizures as a consequence.