Armcx1 Reduces Neurological Damage Via a Mitochondrial Transport Pathway Involving Miro1 After Traumatic Brain Injury.

Armcx1 is a member of the ARMadillo repeat-Containing protein on the X chromosome (ARMCX) family, which is recognized to have evolutionary conserved roles in regulating mitochondrial transport and dynamics. Previous research has shown that Armcx1 is expressed at higher levels in mice after axotomy and in adult retinal ganglion cells after crush injury, and this protein increases neuronal survival and axonal regeneration. However, its role in traumatic brain injury (TBI) is unclear. Therefore, the aim of this study was to assess the expression of Armcx1 after TBI and to explore possible related mechanisms by which Armcx1 is involved in TBI. We used C57BL/6 male mice to model TBI and evaluated the role of Armcx1 in TBI by transfecting mice with Armcx1 small interfering RNA (siRNA) to inhibit Armcx1 expression 24 h before TBI modeling. Western blotting, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Nissl staining, transmission electron microscopy, adenosine triphosphate (ATP) level measurement, neuronal apoptosis analysis, neurological function scoring and the Morris water maze were performed. The results demonstrated that Armcx1 protein expression was elevated after TBI and that the Armcx1 protein was localized in neurons and astroglial cells in cortical tissue surrounding the injury site. In addition, inhibition of Armcx1 expression further led to impaired mitochondrial transport, abnormal morphology, reduced ATP levels, aggravation of neuronal apoptosis and neurological dysfunction, and decrease Miro1 expression. In conclusion, our findings indicate that Armcx1 may exert neuroprotective effects by ameliorating neurological injury after TBI through a mitochondrial transport pathway involving Miro1.

Primary acinic cell carcinoma of the breast: A case report and review of literature.

BACKGROUND: In the current World Health Organization classification, acinic cell carcinoma (AcCC) of the breast is considered a rare histological subtype of triple-negative breast cancer. Because of the few reports in the literature, data concerning clinical outcomes are limited. Here, we report a case of AcCC of the breast in a 48-year-old woman. CASE SUMMARY: A 48-year-old woman with a mass in her right breast came to our hospital for further diagnosis. Mammography and an ultrasound (US) scan showed a mass in the upper inner side of the right breast. She then underwent surgery to resect the mass in her right breast. Postoperative pathological examination revealed that the tumor had abundant acinar-like structures formed by tumor cells with prominent eosinophilic granules in the cytoplasm, consistent with acinar cell carcinoma. The results of immunohistochemical analysis supported the diagnosis of breast acinar cell carcinoma. Two months later, she underwent breast-conserving surgery and sentinel lymph node biopsy. The pTNM stage was T2N0M0. After surgery, the patient received 30 radiotherapy sessions. The patient was followed up for a period of one year, and no recurrence was found. CONCLUSION: AcCC of the breast is a rare type of malignant tumor. Because it is usually asymptomatic and can be detected by imaging studies, routine breast US or mammograms are important. However, there are no characteristic diagnostic imaging findings or clinical manifestations, so immunohistochemical examination is critical for an accurate diagnosis of AcCC of the breast.

Transient Receptor Potential Mucolipin-1 Participates in Intracerebral Hemorrhage-Induced Secondary Brain Injury by Inducing Neuroinflammation and Neuronal Cell Death.

Transient receptor potential mucolipin-1 (TRPML1) is the most abundantly and widely expressed channel protein in the TRP family. While numerous studies have been conducted involving many aspects of TRPML1, such as its role in cell biology, oncology, and neurodegenerative diseases, there are limited reports about what role it plays in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Here we examined the function of TRPML1 in ICH-induced SBI. The caudal arterial blood of rats was injected into the caudate nucleus of basal ganglia to establish an experimental ICH model. We observed that lentivirus downregulated the expression level of TRPML1 and chemical agonist promoted the enzyme activity of TRPML1. The results indicated that the protein levels of TRPML1 in brain tissues increased 24 h after ICH. These results suggested that downregulated TRPML1 could significantly reduce inflammatory cytokines, and ICH induced the production of LDH and ROS. Furthermore, TRPML1 knockout relieved ICH-induced neuronal cell death and degeneration, and declines in learning and memory after ICH could be improved by downregulating the expression of TRPML1. In addition, chemical agonist-expressed TRPML1 showed the opposite effect and exacerbated SBI after ICH. In summary, this study demonstrated that TRPML1 contributed to brain injury after ICH, and downregulating TRPML1 could improve ICH-induced SBI, suggesting a potential target for ICH therapy.

Therapeutic applications of hydrogen sulfide and novel donors for cerebral ischemic stroke: a narrative review.

Ischemic stroke happens when the blood supply to the brain is obstructed and it is associated with numerous complex mechanisms, such as activated apoptosis genes, oxidative stress and reaction of inflammation, which finally result in neurological deficits. Several gases have been proved to have neuroprotective roles, even the classic gases that are thought to be toxic such as hydrogen sulfide (H2S). H2S is the third identified endogenous gas signaling molecule following carbon monoxide and nitric oxide. H2S plays a significant role in stroke. Inhalation of H2S can attenuate cerebral infarct volume and promote neurological function in a rat model of middle cerebral artery occlusion to reduce ischemic stroke-induced injury in vivo and in vitro as a result. Therefore, H2S can be clinically used to reduce ischemic stroke-induced injury. This review introduces the toxic mechanisms and effects of H2S on cerebral ischemic stroke.

Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation.

Paragangliomas are rare neuroendocrine tumors that originate in the chromaffin cells of the adrenal medulla or lymph nodes. Paragangliomas manifest in rare cases as catecholamine crisis, leading to heart failure, intracranial hemorrhage, renal failure, arrhythmias, pulmonary edema, or multisystem failure. Takotsubo cardiomyopathy is also called apical ballooning syndrome or stress cardiomyopathy. Left ventricular dysfunction with apical hyperkinesis and basilar and midventricular akinesis in the absence of coronary artery disease is highly suggestive of a variant of stress cardiomyopathy (inverted takotsubo cardiomyopathy). Herein, we report the case of a 69-year-old man with an unknown retroperitoneal paraganglioma who suffered from cardiogenic shock due to inverted takotsubo cardiomyopathy. He was treated with venoarterial extracorporeal membrane pulmonary oxygenation (ECMO) in combination with an intra-aortic balloon pump. After the restoration of cardiac function, a successful transition to curative retroperitoneal paraganglioma resection was performed. We conclude that ECMO is a valuable option for undiagnosed endocrine emergencies, helping to restore cardiac function and allowing sufficient time for further accurate diagnosis and specific treatment.

The role of Tenascin C in intracerebral hemorrhage-induced secondary brain injury in rats via induction of neuronal cell death and neuroinflammation.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a major cause of stroke that causes high rates of disability and mortality in adults. Tenascin C (TNC) protein, one of the matricellular proteins associated with platelet-derived growth factor receptor (PDGFR) activation, has been reported to induce neuronal apoptosis. However, the role and underlying mechanisms of TNC in ICH-induced secondary brain injury (SBI) have not yet been fully explained. The main purpose of this study was to explore the role of TNC and its potential mechanisms in ICH. METHODS: An ICH model was established by injecting autologous blood into the right basal ganglia in male Sprague Dawley (SD) rats, and imatinib, an inhibitor of PDGFR, was used to inhibit the release of TNC. RESULTS: We found that TNC protein was significantly increased in the brain tissues after ICH and expressed in both neurons and microglia. We also found that the TNC level was elevated in the cerebrospinal fluid (CSF) after ICH. Additionally, we observed that the infiltration of activated microglia and the release of TNFα and IL-1ß induced by ICH were decreased after inhibition of the protein levels of TNC and cleaved-TNC by a chemical inhibitor (imatinib). Furthermore, imatinib improved neuronal cell death and neurobehavioral abnormalities induced by ICH. CONCLUSION: In summary, our study revealed that TNC protein plays an important role in ICH-induced SBI, and inhibition of TNC could alleviate ICH-induced neuroinflammation, neuronal cell death, and neurobehaviour. Therefore, TNC may be a potential therapeutic target for ICH-induced SBI.

TREM2 modulates neuroinflammation with elevated IRAK3 expression and plays a neuroprotective role after experimental SAH in rats.

BACKGROUND: The modulation of neuroinflammation is a new direction that may alleviate the early brain injury after subarachnoid hemorrhage (SAH). Brain resident microglia/macrophages (Mi/MΦ) are the key drivers of neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to play a neuroprotective role by activating phagocytosis and suspending inflammatory response in experimental ischemic stroke and intracerebral hemorrhage. This study was designed to investigate the role of TREM2 on neuroinflammation and neuroprotective effects in a rat SAH model. METHODS: Adult male Sprague-Dawley rats were induced SAH through endovascular perforation. Lentivirus vectors were administered by i.c.v. to induce TREM2 overexpression or knockdown 7 days before SAH induction. Short- and long-term neurobehavioral tests, western blotting, immunofluorescence, enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining were performed to explore the neuroprotective role of TREM2 after SAH. RESULTS: The expression of TREM2 elevated in a rat SAH model with a peak at 48 h after SAH and mainly expressed in Mi/MΦ in brain. TREM2 overexpression improved short- and long-term neurological deficits induced by SAH in rats, while TREM2 knockdown worsened neurological dysfunction. The rats with TREM2 overexpressed presented less neuronal apoptosis and more neuronal survival at 48 h after SAH, while the rats with TREM2 knockdown presented on the contrary. TREM2 overexpression manifested activated phagocytosis and suppressed inflammatory response, with the increase of CD206+/CD11b+ cells and IL-10 expression as well as the decrease of the infiltration of MPO+ cells and the expression of TNF-α, IL-1ß. While TREM2 knockdown abolished these effects. The protein level of IRAK3, a negative regulatory factor of inflammation, was significantly elevated after TREM2 overexpression and declined after TREM2 knockdown. CONCLUSIONS: Our research suggested TREM2 played a neuroprotective role and improved the short- and long-term neurological deficits by modulating neuroinflammation after SAH. The modulation on neuroinflammation of TREM2 after SAH was related with the elevated protein level of IRAK3.

Role of hyperbaric oxygen in glioma: a narrative review.

Gliomas are common brain mass with a high mortality rate. Patients with gliomas have a severely bad outcome, with an average survive duration less 15 months because of high recurrent rate and being resistant to radio-therapy and chemistry drugs therapy. Hyperbaric oxygen is extensively taken as an adjuvant treatment for various disease conditions. To know the characteristics of hyperbaric oxygen as a remedy for gliomas, we find that, in general, hyperbaric oxygen shows an obviously positive effect on the treatment of gliomas, and it can also relieve the complications caused by postoperative radiotherapy and chemotherapy of gliomas. Whereas, several researches have shown that hyperbaric oxygen promotes glioma progression.

A narrative review of adjuvant therapy for glioma: hyperbaric oxygen therapy.

Glioma is a kind of common malignant tumor in neurosurgery and has a high mortality and morbidity rate, which poses a serious threat to the health of people all over the world. Surgery is the preferred treatment for patients with glioma, radiotherapy or chemotherapy can be used after surgery. Although there are clear therapeutic protocols, the efficacy and safety of these protocols are clinically proven, a large number of patients are still dissatisfied with the treatment and the health of the patient remains unsatisfactory. Therefore, it is crucial to look for other treatments or complementary treatments. In the modern medical treatment, hyperbaric oxygen (HBO) therapy is widely used in various kinds of pathological state of adjuvant therapy, and existing studies confirm the efficacy of HBO therapy in combination with surgery, radiotherapy, chemotherapy, and photodynamic therapy. Studies have shown that HBO can inhibit the growth of tumor tissue as an adjunctive therapy. This provides novel insights into the clinical treatment of glioma patients. Although HBO is not licensed for use in cancer treatment, as a kind of adjuvant therapy, the treatment effect of HBO can be accepted by the patients and its cost lower, which could be regarded as an ideal safe treatment.

Loss of MIC60 Aggravates Neuronal Death by Inducing Mitochondrial Dysfunction in a Rat Model of Intracerebral Hemorrhage.

Mitochondrial damage has been reported to be a critical factor for secondary brain injury (SBI) induced by intracerebral hemorrhage (ICH). MIC60 is a key element of the mitochondrial contact site and cristae junction organizing system (MICOS), which takes a principal part in maintaining mitochondrial structure and function. The role of MIC60 and its underlying mechanisms in ICH-induced SBI are not clear, which will be investigated in this present study. To establish and emulate ICH model in vivo and in vitro, autologous blood was injected into the right basal ganglia of Sprague-Dawley (SD) rats; and primary-cultured cortical neurons were treated by oxygen hemoglobin (OxyHb). First, after ICH induction, mitochondria were damaged and exhibited mitochondrial crista-structure remodeling, and MIC60 protein levels were reduced. Furthermore, MIC60 overexpression reduced ICH-induced neuronal death both in vivo and in vitro. In addition, MIC60 upregulation reduced ICH-induced cerebral edema, neurobehavioral impairment, and cognitive dysfunction; by contrast, MIC60 knockdown had the opposite effect. Additionally, in primary-cultured neurons, MIC60 overexpression could reverse ICH-induced neuronal cell death and apoptosis, mitochondrial membrane potential collapse, and decrease of mitophagy, indicating that MIC60 overexpression can maintain the integrity of mitochondrial structures. Moreover, loss of MIC60 is after ICH-induced reduction in PINK1 levels and mislocalization of Parkin in primary-cultured neurons. Taken together, our findings suggest that MIC60 plays an important role in ICH-induced SBI and may represent a promising target for ICH therapy.

Galectin-9 Promotes Neuronal Restoration via Binding TLR-4 in a Rat Intracerebral Hemorrhage Model.

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. Galactose lectin-9 (Gal-9) belongs to the family of ß-galactoside-binding lectins, which has been shown to play a vital role in immune tolerance and inflammation. However, the function of Gal-9 in ICH has not been fully studied in details. Several experiments were carried out to explore the role of Gal-9 in the late period of ICH. Primarily, ICH models were established in male adult Sprague Dawley (SD) rats. Next, the relative protein levels of Gal-9 at different time points after ICH were examined and the result showed that the level of Gal-9 increased and peaked at the 7th day after ICH. Then we found that when the content of Gal-9 increased, both the number of M2-type microglia and the corresponding anti-inflammatory factors also increased. Through co-immunoprecipitation (CO-IP) analysis, it was found that Gal-9 combines with Toll-like receptor-4 (TLR-4) during the period of the recovery after ICH. TUNEL staining and Fluoro-Jade B staining (FJB) proved that the amount of cell death decreased with the increase of Gal-9 content. Additionally, several behavioral experiments also demonstrated that when the level of Gal-9 increased, the motor, sensory, learning, and memory abilities of the rats recovered better compared to the ICH group. In short, this study illustrated that Gal-9 takes a crucial role after ICH. Enhancing Gal-9 could alleviate brain injury and promote the recovery of ICH-induced injury, so that Gal-9 may exploit a new pathway for clinical treatment of ICH.

Heterogeneous nuclear ribonucleoprotein A1 exerts protective role in intracerebral hemorrhage-induced secondary brain injury in rats.

Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is the most abundant and expressed widely member of the hnRNP family. It has been extensively studied in developmental biology, oncology, and neurodegenerative diseases, which has not been reported on in intracerebral hemorrhage (ICH) induced-secondary brain injury (SBI). The purpose of this study was to explore the role of hnRNPA1 exerts and its underlying mechanism in ICH-induced SBI. Experimental ICH models were established by injecting autologous heart blood into the basal ganglia region of rats and increased or inhibited hnRNPA1 expression through the hnRNPA1 plasmid and small interfering RNA. The results illustrated that the protein levels of hnRNPA1 are significantly elevated after ICH, and hnRNPA1 is transported from the nucleus to the cytoplasm. Upregulated hnRNPA1 could improve neurological function and the learning and memory ability decline after ICH-induced injury. Furthermore, TUNEL and FJB staining indicated that hnRNPA1 overexpression could reduce neuronal cell death and injury induced by ICH. However, downregulated hnRNPA1 damages neurological function and learning and memory abilities and aggravates neuronal cell degeneration and apoptosis. Consistently, the levels of Bcl-xl mRNA and Bcl-xl are elevated or decreased depending on the levels of hnRNPA1, which could be one of the mechanisms through which hnRNPA1 participates in ICH-induced neuronal cell death. In summary, hnRNPA1 plays a protective role in ICH-induced SBI via upregulating Bcl-xl expression, indicating that hnRNPA1 could be a potential target for ICH therapy.

Luteolin Exerts Neuroprotection via Modulation of the p62/Keap1/Nrf2 Pathway in Intracerebral Hemorrhage.

Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch-like enoyl-coenzyme A hydratase (ECH)-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.