Acute kidney injury (AKI) is an inflammatory sequence. It can lead to distant organ injury, including damage to the central nervous system (CNS), mediated by increased circulating cytokines and other inflammatory mediators. It can also lead to increased blood–brain barrier (BBB) permeability. However, the effect of AKI on the inflammatory response of the brain has not yet been investigated. Therefore, we observed the effect of AKI on BBB permeability, microglia and astrocyte activation, and neuronal toxicity in the brain. The striatum and ventral midbrain, known to control overall movement, secrete the neurotransmitter dopamine. The activation of microglia and astrocytes present in this area causes neuro-degenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The activation of astrocytes and microglia in the hippocampus and cerebral cortex, which are responsible for important functions, including memory, learning, concentration, and language, can trigger nerve cell apoptosis. The activation of astrocytes and microglia at this site is also involved in the inflammatory response associated with the accumulation of beta-amyloid. In the situation of kidney ischemia reperfusion (IR)-induced AKI, activation of microglia and astrocytes were observed in the striatum, ventral midbrain, hippocampus, and cortex. However, neuronal cell death was not observed until 48 h.

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1^‐/‐ mice. Further, we show that A1‐reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV‐infected IFNAR1^‐/‐ mice also induced neuronal cell death through the activation of A1‐reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.

Background/Objectives: Parkinson’s disease (PD) is a neuro-degenerative disease for which a radical cure is not available, only symptomatic control. Studies have shown that hypoxia may have disease-modifying effects on PD. Methods: Herein, we investigated whether short-term hypoxia activates astrocytes and whether it has a protective effect on pre-formed fibril (PFF)-treated primary cortical neurons. Results: Long-term hypoxia suppresses astrocyte activation and induces cell death, whereas short-term hypoxia activates astrocytes without affecting cellular apoptosis or viability. Short-term hypoxia restored the cellular apoptosis and viability of PFF-treated neurons and reduced toxic phospho-α-synuclein (p-α-syn) aggregation. Similarly, the short-term hypoxia-exposed astrocyte-conditioned medium rescued cellular apoptosis and the viability of PFF-treated neurons and p-α-syn expression. Quantitative polymerase chain reaction revealed that short-term hypoxia promotes protective A2 astrocytes and suppresses toxic A1 astrocytes. Conclusions: Our findings suggest that short-term hypoxia has a neuro-protective effect against PD by activating protective A2 astrocytes, which rescue PFF-induced neuronal cell death. This provides insights into the clinical implications of short-term hypoxia as a disease-modifying PD strategy.

PURPOSE: Exercise training is widely recognized as a complementary intervention that provides both therapeutic and preventive benefits for neurodegenerative diseases, given its strong association with brain health. Regulating the expression of neurotrophic factors can significantly enhance cognitive function and memory processes, particularly in conditions such as Alzheimer’s disease (AD). However, the effects of high-intensity interval aerobic exercise training (HIE) on brain-derived neurotrophic factors and astrocyte activation in the cortex (CTX) and the hippocampus (HIP) remain unclear. Therefore, this study aimed to investigate whether HIE regulates the expression of neurotrophic factors and neuroinflammatory cytokines in the CTX and HIP.METHODS: Eighteen-week-old female C57BL/6 mice were assigned to control (Cnt) and HIE groups. After 12 weeks of HIE, the brains were harvested for immunoblotting, immunofluorescence, real-time PCR (qRT-PCR), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays.RESULTS: HIE increased the expression of glial cell line-derived neurotrophic factor (GDNF) protein in the CTX but not in the HIP. Additionally, HIE exerted a protective effect against neuroinflammation by significantly upregulating A2-specific astrocytic transcripts. These findings suggest that HIE promotes neurotrophic and anti-inflammatory responses in both CTX and HIP.CONCLUSIONS: Our study results suggest that HIE exerts protective regulatory effects on neurotrophic factors, neuroinflammation, and A1/A2 type astrocytic reactivity in CTX and HIP of animal models. These findings suggest that HIE has beneficial effects on brain health. However, as these results were derived from animal studies, further clinical research is required to determine whether similar neuroprotective effects can be observed in humans.