The role of the astrocyte in subarachnoid hemorrhage and its therapeutic implications.

Subarachnoid hemorrhage (SAH) is an important public health concern with high morbidity and mortality worldwide. SAH induces cell death, blood-brain barrier (BBB) damage, brain edema and oxidative stress. As the most abundant cell type in the central nervous system, astrocytes play an essential role in brain damage and recovery following SAH. This review describes astrocyte activation and polarization after SAH. Astrocytes mediate BBB disruption, glymphatic-lymphatic system dysfunction, oxidative stress, and cell death after SAH. Furthermore, astrocytes engage in abundant crosstalk with other brain cells, such as endothelial cells, neurons, pericytes, microglia and monocytes, after SAH. In addition, astrocytes also exert protective functions in SAH. Finally, we summarize evidence regarding therapeutic approaches aimed at modulating astrocyte function following SAH, which could provide some new leads for future translational therapy to alleviate damage after SAH.

Mitochondrial Dynamics: A Potential Therapeutic Target for Ischemic Stroke.

Stroke is one of the leading causes of death and disability worldwide. Brain injury after ischemic stroke involves multiple pathophysiological mechanisms, such as oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium overload, neuroinflammation, neuronal apoptosis, and blood-brain barrier (BBB) disruption. All of these factors are associated with dysfunctional energy metabolism after stroke. Mitochondria are organelles that provide adenosine triphosphate (ATP) to the cell through oxidative phosphorylation. Mitochondrial dynamics means that the mitochondria are constantly changing and that they maintain the normal physiological functions of the cell through continuous division and fusion. Mitochondrial dynamics are closely associated with various pathophysiological mechanisms of post-stroke brain injury. In this review, we will discuss the role of the molecular mechanisms of mitochondrial dynamics in energy metabolism after ischemic stroke, as well as new strategies to restore energy homeostasis and neural function. Through this, we hope to uncover new therapeutic targets for the treatment of ischemic stroke.

Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke.

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

The Application of Brain Organoid Technology in Stroke Research: Challenges and Prospects.

Stroke is a neurological disease responsible for significant morbidity and disability worldwide. However, there remains a dearth of effective therapies. The failure of many therapies for stroke in clinical trials has promoted the development of human cell-based models, such as brain organoids. Brain organoids differ from pluripotent stem cells in that they recapitulate various key features of the human central nervous system (CNS) in three-dimensional (3D) space. Recent studies have demonstrated that brain organoids could serve as a new platform to study various neurological diseases. However, there are several limitations, such as the scarcity of glia and vasculature in organoids, which are important for studying stroke. Herein, we have summarized the application of brain organoid technology in stroke research, such as for modeling and transplantation purposes. We also discuss methods to overcome the limitations of brain organoid technology, as well as future prospects for its application in stroke research. Although there are many difficulties and challenges associated with brain organoid technology, it is clear that this approach will play a critical role in the future exploration of stroke treatment.

Preconditioning increases brain resistance against acute brain injury via neuroinflammation modulation.

Acute brain injury (ABI) is a broad concept mainly comprised of sudden parenchymal brain injury. Acute brain injury outcomes are dependent not only on the severity of the primary injury, but the delayed secondary injury that subsequently follows as well. These are both taken into consideration when determining the patient's prognosis. Growing clinical and experimental evidence demonstrates that "preconditioning," a prophylactic approach in which the brain is exposed to various pre-injury stressors, can induce varying degrees of "tolerance" against the impact of the ABI by modulating neuroinflammation. In this review, we will summarize the pathophysiology of ABI, and discuss the involved mechanisms of neuroinflammation in ABI, as well as existing experimental and clinical studies demonstrating the efficacy of preconditioning methods in various types of ABI by modulating neuroinflammation.

The Role of Nanomaterials in Stroke Treatment: Targeting Oxidative Stress.

Stroke has a high rate of morbidity and disability, which seriously endangers human health. In stroke, oxidative stress leads to further damage to the brain tissue. Therefore, treatment for oxidative stress is urgently needed. However, antioxidative drugs have demonstrated obvious protective effects in preclinical studies, but the clinical studies have not seen breakthroughs. Nanomaterials, with their characteristically small size, can be used to deliver drugs and have demonstrated excellent performance in treating various diseases. Additionally, some nanomaterials have shown potential in scavenging reactive oxygen species (ROS) in stroke according to the nature of nanomaterials. The drugs' delivery ability of nanomaterials has great significance for the clinical translation and application of antioxidants. It increases drug blood concentration and half-life and targets the ischemic brain to protect cells from oxidative stress-induced death. This review summarizes the characteristics and progress of nanomaterials in the application of antioxidant therapy in stroke, including ischemic stroke, hemorrhagic stroke, and neural regeneration. We also discuss the prospect of nanomaterials for the treatment of oxidative stress in stroke and the challenges in their application, such as the toxicity and the off-target effects of nanomaterials.

Insight Into the Mechanisms and the Challenges on Stem Cell-Based Therapies for Cerebral Ischemic Stroke.

Strokes are the most common types of cerebrovascular disease and remain a major cause of death and disability worldwide. Cerebral ischemic stroke is caused by a reduction in blood flow to the brain. In this disease, two major zones of injury are identified: the lesion core, in which cells rapidly progress toward death, and the ischemic penumbra (surrounding the lesion core), which is defined as hypoperfusion tissue where cells may remain viable and can be repaired. Two methods that are approved by the Food and Drug Administration (FDA) include intravenous thrombolytic therapy and endovascular thrombectomy, however, the narrow therapeutic window poses a limitation, and therefore a low percentage of stroke patients actually receive these treatments. Developments in stem cell therapy have introduced renewed hope to patients with ischemic stroke due to its potential effect for reversing the neurological sequelae. Over the last few decades, animal tests and clinical trials have been used to treat ischemic stroke experimentally with various types of stem cells. However, several technical and ethical challenges must be overcome before stem cells can become a choice for the treatment of stroke. In this review, we summarize the mechanisms, processes, and challenges of using stem cells in stroke treatment. We also discuss new developing trends in this field.

The Role of Iron, Its Metabolism and Ferroptosis in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a structural and physiological disruption of brain function caused by external forces. It is a major cause of death and disability for patients worldwide. TBI includes both primary and secondary impairments. Iron overload and ferroptosis highly involved in the pathophysiological process of secondary brain injury. Ferroptosis is a form of regulatory cell death, as increased iron accumulation in the brain leads to lipid peroxidation, reactive oxygen species (ROS) production, mitochondrial dysfunction and neuroinflammatory responses, resulting in cellular and neuronal damage. For this reason, eliminating factors like iron deposition and inhibiting lipid peroxidation may be a promising therapy. Iron chelators can be used to eliminate excess iron and to alleviate some of the clinical manifestations of TBI. In this review we will focus on the mechanisms of iron and ferroptosis involving the manifestations of TBI, broaden our understanding of the use of iron chelators for TBI. Through this review, we were able to better find novel clinical therapeutic directions for further TBI study.

Dyella monticola sp. nov. and Dyella psychrodurans sp. nov., isolated from monsoon evergreen broad-leaved forest soil of Dinghu Mountain, China.

Cells of bacterial strains 4 G-K06T and 4MSK11T, isolated from soil samples collected from monsoon evergreen broad-leaved forest of the Dinghushan Mountain (112° 31' E 23° 10' N), Guangdong Province, PR China, were Gram-stain-negative, aerobic, non-spore-forming, non-motile and rod-shaped. Strain 4 G-K06T grew at 10-37 °C, pH 3.5-7.5 and 0-3.5 % (w/v) NaCl; while 4MSK11T grew at 4-42 °C, pH 3.5-7.5 and 0-2.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed strain 4 G-K06T formed a clade with Dyellaflagellata 4 M-K16T, Dyella acidisoli 4M-Z03T, Dyellahumi DHG40T and Dyellanitratireducens DHG59T, while strain 4MSK11T formed a clade with Dyellacaseinilytica DHOB09T and Dyellamobilis DHON07T, both within the genus Dyella. The result of the partial atpD, gyrB and lepA gene sequence analysis supported the conclusion based on 16S rRNA gene sequence analysis, which showed that these two strains represent two novel species of Dyella. The average nucleotide identity and digital DNA-DNA hybridization value for the whole genomes were 75.0-79.0 and 20.3-22.6 % between strains 4 G-K06T, 4MSK11T and those described Dyella species with genome sequences; while the DNA-DNA hybridization rates between strains 4 G-K06T, 4MSK11T and closely related Dyella species (without genome sequence) were 29.5-41.8 %. The major cellular fatty acids of these two strains were iso-C15 : 0, iso-C16 : 0 and iso-C17 : 1ω9c, while the major polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several unidentified phospholipids and aminophospholipids. The only ubiquinone of these two strains was ubiquinone-8. The DNA G+C contents of 4 G-K06T and 4MSK11T were 60.4 and 61.3 mol%, respectively. On the basis of the evidence presented here, strains 4 G-K06T and 4MSK11T represent two novel species of the genus Dyella, for which the names Dyella monticola sp. nov. (type strain 4 G-K06T=LMG 30268T=GDMCC 1.1188T) and Dyella psychrodurans sp. nov. (type strain 4MSK11T=KCTC 62280T=GDMCC 1.1185T) are proposed.

Dyella acidisoli sp. nov., D. flagellata sp. nov. and D. nitratireducens sp. nov., isolated from forest soil.

Bacterial strains 4M-Z03T, 4M-K16T and DHG59T were isolated from forest soil samples collected from the Dinghushan Biosphere Reserve, Guangdong Province, PR China (112° 31' E 23° 10' N). The three strains grew well at 28 °C, pH 5.0-6.0 on R2A medium. On the basis of 16S rRNA gene sequence analysis, the three strains, together with Dyella humi DHG40T, formed a distinct phyletic clade within the genus Dyella, and the sequence similarities between any strains of the clade ranged from 97.8 to 98.5 %. Sequence analysis of concatenated partial gyrB, lepA and recA gene sequences also strongly suggested that the three strains represented three novel species of the genus Dyella. The respiratory lipoquinone of the three strains was ubiquinone-8, and their DNA G+C content was 58.2-59.0 mol%. The fatty acid profiles differed substantially among these three strains, although they had two common major fatty acids, iso-C15 : 0 and iso-C17 : 1ω9c. The DNA-DNA relatedness among the three strains and the type strains of the closest species of the genus Dyella examined was lower than 50 %. The results of genotypic and phenotypic characterization presented above demonstrate that the three strains examined represent three novel species of the genus Dyella, for which the names Dyella acidisoli sp. nov. (type strain 4M-Z03T=NBRC 111980T=KCTC 52131T), Dyella flagellata sp. nov. (type strain 4M-K16T=NBRC 111981T=KCTC 52130T) and Dyella nitratireducens sp. nov. (type strain DHG59T=NBRC 111472T=LMG 29201T=CGMCC 1.15439T) are proposed.

Aliidongia dinghuensis gen. nov., sp. nov., a poly-ß-hydroxybutyrate-producing bacterium isolated from Pinus massoniana forest soil.

A Gram-stain-negative, aerobic, motile, rod-shaped bacterium, designated 7M-Z19T, was isolated from a soil sample collected from a Pinus massoniana forest of Dinghushan Biosphere Reserve, Guangdong Province, PR China. Strain 7M-Z19T grew at pH 4.5-7.5 (optimum pH 6.0-6.5), 10 to 37 °C (optimum 28 °C) and NaCl concentration up to 2.0 % (optimum 0 %, w/v). iso-C17 : 0, C18 : 1ω7c and C19 : 0ω8c cyclo were the major fatty acids (>10 %) while ubiquinone-10 was the only respiratory quinone detected in 7M-Z19T. The polar lipids of the strain consisted of phosphatidylethanolamine, phosphatidyldimethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, six unidentified aminophospholipids, three unidentified phospholipids, six unidentified lipids and a glycolipid. The DNA G+C content was 65.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate formed a distinct lineage with Dongia mobilis and Dongia rigui within the family Rhodospirillaceae, but with a low sequence similarity of 92.7 and 92.0 %, respectively. On the basis of phylogenetic, phenotypic, physiological and chemotaxonomic distinctiveness, strain 7M-Z19T should be placed in the family Rhodospirillaceae as a representative of a novel genus and species, for which the name Aliidongia dinghuensis gen. nov., sp. nov., is proposed. The type strain of the type species is 7M-Z19T (=NBRC 112240T=KCTC 52134T=CGMCC 1.15725T).