Traumatic brain injury (TBI) is one of the most common pathological conditions impacting the central nervous system (CNS). A neurological deficit associated with TBI results from a complex of pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or the development of edema. The critical components contributing to CNS response, damage control, and regeneration after TBI are glial cells-in reaction to tissue damage, their activation, hypertrophy, and proliferation occur, followed by the formation of a glial scar. The glial scar creates a barrier in damaged tissue and helps protect the CNS in the acute phase post-injury. However, this process prevents complete tissue recovery in the late/chronic phase by producing permanent scarring, which significantly impacts brain function. Various glial cell types participate in the scar formation, but this process is mostly attributed to reactive astrocytes and microglia, which play important roles in several brain pathologies. Novel technologies including whole-genome transcriptomic and epigenomic analyses, and unbiased proteomics, show that both astrocytes and microglia represent groups of heterogenic cell subpopulations with different genomic and functional characteristics, that are responsible for their role in neurodegeneration, neuroprotection and regeneration. Depending on the representation of distinct glia subpopulations, the tissue damage as well as the regenerative processes or delayed neurodegeneration after TBI may thus differ in nearby or remote areas or in different brain structures. This review summarizes TBI as a complex process, where the resultant effect is severity-, region- and time-dependent and determined by the model of the CNS injury and the distance of the explored area from the lesion site. Here, we also discuss findings concerning intercellular signaling, long-term impacts of TBI and the possibilities of novel therapeutical approaches. We believe that a comprehensive study with an emphasis on glial cells, involved in tissue post-injury processes, may be helpful for further research of TBI and be the decisive factor when choosing a TBI model.

Acquired traumatic central nervous system (CNS) injuries, including traumatic brain injury (TBI) and spinal cord injury (SCI), are devastating conditions with limited treatment options. Neuroinflammation plays a pivotal role in secondary damage, making it a prime target for therapeutic intervention. Emerging therapeutic strategies are designed to modulate the inflammatory response, ultimately promoting neuroprotection and neuroregeneration. The use of anti-inflammatory agents has yielded limited support in improving outcomes in patients, creating a critical need to re-envision novel approaches to both quell deleterious inflammatory processes and upend the progressive cycle of neurotoxic inflammation. This demands a comprehensive exploration of individual, age, and sex differences, including the use of advanced imaging techniques, multi-omic profiling, and the expansion of translational studies from rodents to humans. Moreover, a holistic approach that combines pharmacological intervention with multidisciplinary neurorehabilitation is crucial and must include both acute and long-term care for the physical, cognitive, and emotional aspects of recovery. Ongoing research into neuroinflammatory biomarkers could revolutionize our ability to predict, diagnose, and monitor the inflammatory response in real time, allowing for timely adjustments in treatment regimens and facilitating a more precise evaluation of therapeutic efficacy. The management of neuroinflammation in acquired traumatic CNS injuries necessitates a paradigm shift in our approach that includes combining multiple therapeutic modalities and fostering a more comprehensive understanding of the intricate neuroinflammatory processes at play.

It is increasingly evident that cells and molecules of the immune system play significant roles in neurodevelopment. As perinatal infection is associated with the development of neurodevelopmental disorders, previous research has focused on demonstrating that the induction of neuroinflammation in the developing brain is capable of causing neuropathology and behavioral changes. Recent studies, however, have revealed that immune cells and molecules in the brain can influence neurodevelopment without the induction of overt inflammation, identifying neuroimmune activities as integral parts of normal neurodevelopment. This mini-review describes the shift in literature that has moved from emphasizing the intrusion of inflammatory events as a main culprit of neurodevelopmental disorders to evaluating the deviation of the normal neuroimmune activities in neurodevelopment as a potential pathogenic mechanism.

Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases, and although most studies focus on its effects on neuronal cells, the contribution of non-neuronal cells to the improvement triggered by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested. To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases, Web of Science and PubMed were searched for the effects of high-frequency-repetitive transcranial magnetic stimulation, low-frequency-repetitive transcranial magnetic stimulation, intermittent theta-burst stimulation, continuous theta-burst stimulation, or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells. A total of 52 studies were included. The protocol more frequently used was high-frequency-repetitive magnetic stimulation, and in models of disease, most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and microglial reactivity, a decrease in the release of pro-inflammatory cytokines, and an increase of oligodendrocyte proliferation. The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation. Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol, and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines, reporting the absence of effects on these parameters. In what concerns the use of magnetic stimulation in unlesioned animals or cells, most articles on all four types of stimulation reported a lack of effects. It is also important to point out that the studies were developed mostly in male rodents, not evaluating possible differential effects of repetitive transcranial magnetic stimulation between sexes. This systematic review supports that through modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models. However, it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects, emphasizing the need for more studies in this field.

Exposure to stress during early development may lead to altered neurobiological functions, thus increasing the risk for psychiatric illnesses later in life. One potential mechanism associated with those outcomes is the disruption of glial density and morphology, despite results from rodent studies have been conflicting. To address that we performed a systematic review and meta-analysis of rodent studies that investigated the effects of prenatal stress (PNS) and early life stress (ELS) on microglia, astrocyte, and oligodendrocyte density and morphology within the offspring. Our meta-analysis demonstrates that animals exposed to PNS or ELS showed significant increase in microglia density, as well as decreased oligodendrocyte density. Moreover, ELS exposure induced an increase in microglia soma size. However, we were unable to identify significant effects on astrocytes. Meta-regression indicated that experimental stress protocol, sex, age, and type of tissue analyzed are important covariates that impact those results. Importantly, PNS microglia showed higher estimates in young animals, while the ELS effects were stronger in adult animals. This set of data reinforces that alterations in glial cells could play a role in stress-induced dysfunctions throughout development.

Ischemic stroke is common in the elderly, and is one of the main causes of long-term disability worldwide. After ischemic stroke, spontaneous recovery and functional reconstruction take place. These processes are possible thanks to neuroplasticity, which involves neurogenesis, synaptogenesis, and angiogenesis. However, the repair of ischemic damage is not complete, and neurological deficits develop eventually. The WHO recommends acupuncture as an alternative and complementary method for the treatment of stroke. Moreover, clinical and experimental evidence has documented the potential of acupuncture to ameliorate ischemic stroke-induced neurological deficits, particularly sequelae such as dyskinesia, spasticity, cognitive impairment, and dysphagia. These effects are related to the ability of acupuncture to promote spontaneous neuroplasticity after ischemic stroke. Specifically, acupuncture can stimulate neurogenesis, activate axonal regeneration and sprouting, and improve the structure and function of synapses. These processes modify the neural network and function of the damaged brain area, producing the improvement of various skills and adaptability. Astrocytes and microglia may be involved in the regulation of neuroplasticity by acupuncture, such as by the production and release of a variety of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Moreover, the evidence presented indicates that acupuncture promotes neuroplasticity by modulating the functional reconstruction of the whole brain after ischemia. Therefore, the promotion of neuroplasticity is expected to become a new target for acupuncture in the treatment of neurological deficits after ischemic stroke, and research into the mechanisms responsible for these actions will be of significant clinical value.

This systematic review examines the effect of photobiomodulation (PBM), the application of red to near infrared light on body tissues, on the neuroinflammatory response and oxidative stress in animal models of neurodegenerative diseases. The research question and search protocol were prospectively registered on the PROSPERO database. Neurodegenerative diseases are becoming ever more prevalent in the ageing populations across the Western world, with no disease-modifying or neuroprotective treatment options being available. Hence there is a real need for the development of effective treatment options for patients. Inflammatory responses and oxidative stress within the central nervous system have a strong correlation with neuronal cell death. PBM is a non-invasive therapeutic option that has shown efficacy and promising effects in animal models of neurodegenerative disease; many studies have reported neuroprotection and improved behavioural outcomes. To the best of our knowledge, there has been no previous study that has reviewed the anti-inflammatory and the antioxidant effect of PBM in the context of neurodegeneration. This review has examined this relationship in animal models of a range of neurodegenerative diseases. We found that PBM can effectively reduce glial activation, pro-inflammatory cytokine expression and oxidative stress, whilst increasing anti-inflammatory glial responses and cytokines, and antioxidant capacity. These positive outcomes accompanied the neuroprotection evident after PBM treatment. Our review provides further indication that PBM can be developed into an effective non-pharmacological intervention for neurodegenerative diseases.

As a traditional Chinese therapy, acupuncture is proposed worldwide as a treatment for pain and other health problems, but findings on acupuncture analgesia have been inconsistent because of its variable modalities of therapeutic intervention.
This study aimed to evaluate the existing animal studies for evidence on acupuncture and its effect on glia in association with a reduction in pain conditions.
Literature searches were performed in four English- and Chinese-language databases (Web of Science, PubMed, EMBASE, and CNKI) on October 8, 2021. Included studies reported the pain outcome (e.g., paw withdrawal latency, paw withdrawal threshold) and glia outcome (e.g., glial marker GFPA, Iba1, and OX42) in pain-induced animals during acupuncture treatment.
Fifty-two preclinical studies were included in the meta-analysis. A single acupuncture treatment in rodents had an analgesic effect, which was more effective in inflammatory pain than in neuropathic pain in the early phase of treatment. The analgesic efficacy became more curative after repeated acupuncture. Furthermore, acupuncture treatment could effectively inhibit the activity of astrocytes and microglia in both inflammatory pain and neuropathic pain in a time-course pattern.
Acupuncture treatment improves analgesic effect in rodent pain conditions under the possible mechanism of glial inhibition. Therefore, these results provide an opportunity to evaluate the effectiveness of acupuncture analgesia and neuroinflammation in animal models to research further neurobiological mechanisms and to inform the design of future clinical trials.
PROSPERO (ID: CRD42020196011).

Epilepsy is a chronic brain disorder that causes repeated seizures. It affects 65 million people worldwide and is a major burden on individuals and health systems. It has been reported that factors leading to ion channel disfuntion, neuronal damage and are all involved in the pathogenesis of epilepsy. The exact etipathogenic mechanism is unknown and appropriate therapeutic targets remain elusive. Recent studies point to a significant contribution by non-neuronal cells, the glia-especially astrocytes and microglia-in the pathophysiology of epilepsy. This review critically evaluates the role of glia-induced hyperexcitability in the pathogenesis of epilepsy to provide a better understanding of the contribution of glia to epilepsy.

Traumatic brain injury (TBI) is a debilitating acquired neurological disorder that afflicts nearly 74 million people worldwide annually. TBI has been classified as more than just a single insult because of its associated risk toward various long-term neurological and neurodegenerative disorders. This risk may be triggered by a series of postinjury secondary molecular and cellular pathology, which may be dependent on the severity of the TBI. Among the secondary injury mechanisms, neuroinflammation may be the most crucial as it may exacerbate brain damage and lead to fatal consequences when prolonged. This Review aimed to elucidate the influence of neuroinflammatory mediators on the TBI functional and pathological outcomes, particularly focusing on inflammatory cytokines which were associated with neuronal dysfunctions in the acute and chronic stages of TBI. These cytokines include interleukins (IL) such as IL-1(beta)β, IL-4, IL-6, IL8, IL-10, IL-18, IL-33 and tumor necrosis factor alpha (TNF-α), which have been extensively studied. Apart from these, IL-2, interferon gamma (IFN-γ), and transforming growth factor-beta (TGF-β) may also play a significant role in the pathogenesis of TBI. These neuroinflammatory mediators may trigger a series of pathological events such as cell death, microglial suppression, and increased catecholaminergic activity. Interestingly, in the acute phase of TBI, most of these mediators may also play a neuroprotective role by displaying anti-inflammatory properties, which may convert to a pro-inflammatory action in the chronic stages post TBI. Early identification and treatment of these mediators may help the development of more effective treatment options for TBI.