The potential neuroprotective effects of Spirulina platensis in a valproic acid-induced experimental model of autism in the siblings of albino rats: targeting PIk3/AKT/mTOR signalling pathway.

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with poor social interaction, communication issues, aberrant motor movements, and limited repetitive interests and behaviour. Spirulina platensis (SP) contains several multi-nutrients and has a wide range of neuroprotective properties.Aim: The target of the current experiment is to detect the protective effects of S. platensis on valproic-induced autism in adult female albino rats' siblings for the first time.Materials and Methods: Twelve Pregnant rats were separated into four main groups; Group I (control); Group II (S. platensis); Group III (autistic group); and Group IV (autistic SP-treated group). Fifteen offspring pups from each group were sacrificed, brain was divided for biochemical analysis as superoxide dismutase and malondialdehyde were evaluated spectrophotometrically while interleukin-6, interleukin-12, Bcl-2-associated X protein, B-cell lymphoma-2, Beclin-1, brain-derived neurotrophic factor were assessed by ELISA, other division of brain were used for gene expression of PI3k, Akt and mTOR pathway, last division of brain were stained using (H&E) and Giemsa stains. Tumour necrosis factor alpha (TNF-α) and Synaptophysin (SYN) markers were used for immunohistochemical staining.Results: Autistic Group (III) showed an increment in levels of MDA, IL-6, IL12 and BAX while showing a decrement in SOD, Bcl-2 and Beclin-1 as well as increased PI3k, Akt and mTOR gene expression. Autistic Group (III) also exhibited hypocellularity and disorganization of hippocampal and prefrontal cortex cells. The autistic SP-treated group (IV) showed improvement in these biochemical markers and pathological changes. Our findings suggest that Spirulina platensis will be significant in managing autism.

Stress-induced tRNA cleavage and tiRNA generation in rat neuronal PC12 cells.

Transfer RNA (tRNA) plays a role in stress response programs involved in various pathological conditions including neurological diseases. Under cell stress conditions, intracellular tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived fragments or tRNA-derived stress-induced RNA (tiRNA). Generated tiRNA contributes to the cell stress response and has potential cell protective effects. However, tiRNA generation under stress conditions in neuronal cells has not been fully elucidated. To examine angiogenin-mediated tiRNA generation in neuronal cells, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which specifically and sensitively detects tiRNA. Oxidative stress induced by arsenite and hydrogen peroxide caused tRNA cleavage and tiRNA generation in PC12 cells. We also demonstrated that oxygen-glucose deprivation, which is an in vitro model of ischemic-reperfusion injury, induced tRNA cleavage and tiRNA generation. In these stress conditions, the amount of generated tiRNA was associated with the degree of morphological cell damage. Time course analysis indicated that generation of tiRNA was prior to severe cell damage and cell death. Angiogenin over-expression did not influence the amount of tiRNA in normal culture conditions; however, it significantly increased tiRNA generation induced by cell stress conditions. Our findings show that angiogenin-mediated tiRNA generation can be induced in neuronal cells by different cell stressors, including ischemia-reperfusion. Additionally, detection of tiRNA could be used as a potential cell damage marker in neuronal cells. Cover Image for this issue: doi: 10.1111/jnc.14191.

tiRNAs as a novel biomarker for cell damage assessment in in vitro ischemia-reperfusion model in rat neuronal PC12 cells.

The disruption of appropriate cellular stress responses is implicated in the pathogenesis of different neurological disorders including ischemic injury. Early diagnosis and treatment are often associated with better prognosis in ischemic stroke patients. Thus, there is an urgent need to improve the speed and accuracy of stroke diagnosis by developing highly sensitive stroke biomarkers. We recently reported that transfer RNA (tRNA) was involved in cell stress response pathways. Under cell stress conditions, mature tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived stress-induced RNA (tiRNA). To study tiRNA generation in an in vitro model of ischemic-reperfusion injury, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which detects 1-methyladenosine (m1A) modification of tRNA. We demonstrated that oxygen-glucose deprivation induced tRNA cleavage and tiRNA generation. Time course analysis showed a dramatic up-regulation of tiRNA generation by oxygen-glucose deprivation (OGD) which started a few minutes after reperfusion. Minocycline, a neuroprotective antibiotic, treatment protected PC12 cells against OGD-reperfusion cell damage resulting in a marked down-regulation of the generated tiRNA. Our findings show that cleavage of tRNA and tiRNA generation in rat neuronal PC12 cells occurs with reperfusion injury and the detection of tiRNA could be used as a potential cell damage marker and treatment effect indicator for this type of injury.

Neuroprotective effects of minocycline and progesterone on white matter injury after focal cerebral ischemia.

Stroke induced white matter injury can induce marked neurological deficits even after relatively small infarcts, due to the tightly packed nature of white matter tracts especially in certain areas in the brain. Many drugs which were successful in the pre-clinical trials failed in clinical trials, which was attributed in part to the focus on grey matter injury completely and ignoring their effect on white matter. In this work we selected two known neuroprotective drugs (minocycline and progesterone) and examined their effect on white matter injury after focal cerebral ischemia/reperfusion injury in rats. Focal cerebral ischemia was induced in male Wistar rats (one-hour ischemia followed by reperfusion). Progesterone and minocycline were administered immediately after reperfusion onset. Infarct size, microglial activation and white matter injury were assessed and compared between the treatment and no-treatment groups and Sham operated animals. Our data showed that both progesterone and minocycline reduced infarct size, microglial activation and white matter injury. This work shows a new neuroprotective mechanism of both drugs, via white matter injury reduction, that can be exploited for stroke management. While the utility of either drugs as a sole agent in the management of stroke is questionable, there is a value of using either drugs as an adjuvant therapy to traditional stroke therapy, making use of the white matter protective effect that would improve outcome and facilitate healing after stroke.

Embolization of the choroidal artery in the treatment of cerebral arteriovenous malformations.

OBJECTIVE The anterior and posterior choroidal arteries are often recruited to supply arteriovenous malformations (AVMs) involving important paraventricular structures, such as the basal ganglia, internal capsule, optic radiation, lateral geniculate body, and medial temporal lobe. Endovascular embolization through these arteries is theoretically dangerous because they supply eloquent territories, are of small caliber, and lack collaterals. This study aimed to investigate the safety and efficacy of embolization through these arteries. METHODS This study retrospectively reviewed 13 patients with cerebral AVMs who underwent endovascular embolization through the choroidal arteries between 2006 and 2014. Embolization was performed as a palliative procedure before open surgery or Gamma Knife radiosurgery. Computed tomography and MRI were performed the day after embolization to assess any surgical complications. The incidence and type of complications and their association with clinical outcomes were analyzed. RESULTS Decreased blood flow was achieved in all patients after embolization. Postoperative CT detected no hemorrhagic complications. In contrast, postoperative MRI detected that 4 of the 13 patients (30.7%) developed infarctions: 3 patients after embolization through the anterior choroidal artery, and 1 patient after embolization through the lateral posterior choroidal artery. Two of the 4 patients in whom embolization was from the cisternal segment of the anterior choroidal artery (proximal to the plexal point) developed symptomatic infarction of the posterior limb of the internal capsule, 1 of whom developed morbidity (7.7%). The treatment-related mortality rate was 0%. Additional treatment was performed in 12 patients: open surgery in 9 and Gamma Knife radiosurgery in 3 patients. Complete obliteration was confirmed by angiography at the last follow-up in 10 patients. Recurrent bleeding from the AVMs did not occur in any of the cases during the follow-up period. CONCLUSIONS Ischemic complications are possible following the embolization of cerebral AVMs through the choroidal artery, even with modern neurointerventional devices and techniques. Although further study is needed, embolization through the choroidal artery may be an appropriate treatment option when the risk of surgery or radiosurgery is considered to outweigh the risk of embolization.

Central Retinal Artery Occlusion after the Endovascular Treatment of Unruptured Ophthalmic Artery Aneurysm: A Case Report and a Literature Review.

Endovascular coil embolization for ophthalmic artery (OphA) aneurysms has a risk of occlusion of the OphA, which can lead to loss of vision. The authors report a patient with unruptured OphA aneurysm which treated with endovascular coiling and were complicated by blindness due to OphA thromboembolic occlusion after the procedure. The OphA successfully recanalized using local intra-arterial fibrinolysis with complete regain of visual acuity. The risk of visual loss due to thromboembolic complications cannot be ignored during endovascular coiling of the OphA aneurysm despite of good retrograde flow during OphA occlusion test using a balloon catheter. Rapid intervention is required for recovering visual disturbance in such a situation.

Exclusively epidural spinal metameric arteriovenous shunts: case report and literature review.

BACKGROUND CONTEXT: Spinal arteriovenous metameric syndrome (SAMS) is a subgroup of spinal arteriovenous malformations (AVMs). Most SAMS cases have intra- and extradural AVMs and suffer from hematomyelia, subarachnoid hemorrhage, or venous congestive myelopathy. PURPOSE: To present a rare case of SAMS in which spinal AVMs were exclusively epidural. We reviewed previous literature and evaluated the feasibility of a treatment strategy using endovascular interventions, followed by surgical obliteration. STUDY DESIGN: A case report and literature review of SAMS. METHODS: We report a case of a 15-year-old boy suffering from SAMS in which epidural venous ectasia because of extradural AVMs caused spinal cord compression. RESULTS: The patient was successfully treated with multiple sessions of transarterial embolization followed by open surgery. After the treatment, his neurologic deficits resolved. Postoperative angiography confirmed complete obliteration of extradural AVMs. CONCLUSIONS: Although exclusively epidural spinal AVM is an uncommon type of SAMS, combined endovascular and surgical interventions can be an effective treatment for AVMs to achieve better radiologic outcomes and complete resolution of patient symptoms.

Immuno-Northern Blotting: Detection of RNA Modifications by Using Antibodies against Modified Nucleosides.

The biological roles of RNA modifications are still largely not understood. Thus, developing a method for detecting RNA modifications is important for further clarification. We developed a method for detecting RNA modifications called immuno-northern blotting (INB) analysis and herein introduce its various capabilities. This method involves the separation of RNAs using either polyacrylamide or agarose gel electrophoresis, followed by transfer onto a nylon membrane and subsequent immunoblotting using antibodies against modified nucleosides for the detection of specific modifications. We confirmed that INB with the antibodies for 1-methyladenosine (m1A), N6-methyladenosine (m6A), pseudouridine, and 5-methylcytidine (m5C) showed different modifications in a variety of RNAs from various species and organelles. INB with the anti-m5C antibody revealed that the antibody cross-reacted with another modification on DNA, suggesting the application of this method for characterization of the antibody for modified nucleosides. Additionally, using INB with the antibody for m1A, which is a highly specific modification in eukaryotic tRNA, we detected tRNA-derived fragments known as tiRNAs under the cellular stress response, suggesting the application for tracking target RNA containing specific modifications. INB with the anti-m6A antibody confirmed the demethylation of m6A by the specific demethylases fat mass and obesity-associated protein (FTO) and ALKBH5, suggesting its application for quantifying target modifications in separated RNAs. Furthermore, INB demonstrated that the knockdown of FTO and ALKBH5 increased the m6A modification in small RNAs as well as in mRNA. The INB method has high specificity, sensitivity, and quantitative capability, and it can be employed with conventional experimental apparatus. Therefore, this method would be useful for research on RNA modifications and metabolism.