{"title":"Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects","authors":"Bhuvi Sachdeva, Punya Sachdeva, Shampa Ghosh, Faizan Ahmad, Jitendra Kumar Sinha","doi":"10.1002/ibra.12094","DOIUrl":"10.1002/ibra.12094","url":null,"abstract":"<p>Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are the most common causes of emotional distress that impair an individual's quality of life. MDD is a chronic mental illness that affects 300 million people across the world. Clinical manifestations of MDD include fatigue, loss of interest in routine tasks, psychomotor agitation, impaired ability to focus, suicidal ideation, hypersomnolence, altered psychosocial functioning, and appetite loss. Individuals with depression also demonstrate a reduced behavioral response while experiencing pleasure, a symptom known as anhedonia. Like MDD, PTSD is a prevalent and debilitating psychiatric disorder resulting from a traumatic incident such as sexual assault, war, severe accident, or natural disaster. Symptoms such as recalling event phases, hypervigilance, irritability, and anhedonia are common in PTSD. Both MDD and PTSD pose enormous socioeconomic burdens across the globe. The search for effective treatment with minimal side effects is still ongoing. Ketamine is known for its anesthetic and analgesic properties. Psychedelic and psychotropic effects of ketamine have been found on the nervous system, which highlights its toxicity. In this article, the effectiveness of ketamine as a potential therapeutic for PTSD and MDD along with its mechanisms of action, clinical trials, and possible side effects have been discussed.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IbrainPub Date : 2023-02-19DOI: 10.1002/ibra.12089
Yong-Min Niu, Steven Z. Du, Rong He
{"title":"TNF-α interference ameliorates brain damage in neonatal hypoxic–ischemic encephalopathy rats by regulating the expression of NT-3 and TRKC","authors":"Yong-Min Niu, Steven Z. Du, Rong He","doi":"10.1002/ibra.12089","DOIUrl":"10.1002/ibra.12089","url":null,"abstract":"<p>The aim of this study is to explore the effect of tumor necrosis factor-α (TNF-α) inhibition in rats with neonatal hypoxic–ischemic encephalopathy (HIE) and ascertain the relevant signaling pathways. The Zea–Longa score was used to evaluate the neurological function of the rats. ImageJ was used for quantification of the brain edema volume. Triphenyl tetrazolium chloride (TTC) staining of brain tissue was performed 24 h after hypoxic–ischemic (HI) to detect right brain infarction. The expression of TNF-α was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Immunofluorescence staining was used to identify the localization of TNF-α; Then, the effective shRNA fragment of TNF-α was used to validate the role of TNF-α in HIE rats, and the change of neurotrofin-3 (NT-3) and tyrosine kinase receptor-C (TRKC) was examined after TNF-α-shRNA lentivirus transfection to determine downstream signaling associated with TNF-α. Protein interaction analysis was carried out to predict the links among TNF-α, NT-3, and TRKC. Cerebral edema volume and infarction increased in the right brain after the HI operation. The Zea–Longa score significantly increased within 24 h after the HI operation. The relative expression of TNF-α was upregulated after the HI operation. TNF-α was highly expressed in the right hippocampus post HI through immunofluorescence staining. Bioinformatics analysis found a direct or an indirect link among TNF-α, NT-3, and TRKC. Moreover, the interference of TNF-α increased the expression of NT-3 and TRKC. TNF-α interference might alleviate brain injury in HIE by upregulating NT-3 and TRKC.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74426926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IbrainPub Date : 2023-02-14DOI: 10.1002/ibra.12092
Ankit Ganeshpurkar, Ravi Singh, Pratigya Tripathi, Qadir Alam, Sairam Krishnamurthy, Ashok Kumar, Sushil K. Singh
{"title":"Effect of sulfonamide derivatives of phenylglycine on scopolamine-induced amnesia in rats","authors":"Ankit Ganeshpurkar, Ravi Singh, Pratigya Tripathi, Qadir Alam, Sairam Krishnamurthy, Ashok Kumar, Sushil K. Singh","doi":"10.1002/ibra.12092","DOIUrl":"https://doi.org/10.1002/ibra.12092","url":null,"abstract":"<p>Alzheimer's disease is a neurodegenerative disease responsible for dementia and other neuropsychiatric symptoms. In the present study, compounds <b>30</b> and <b>33</b>, developed earlier in our laboratory as selective butyrylcholinesterase inhibitors, were tested against scopolamine-induced amnesia to evaluate their pharmacodynamic effect. The efficacy of the compounds was determined by behavioral experiments using the Y-maze and the Barnes maze and neurochemical testing. Both compounds reduced the effect of scopolamine treatment in the behavioral tasks at a dose of 20 mg/kg. The results of the neurochemical experiment indicated a reduction in cholinesterase activity in the prefrontal cortex and the hippocampus. The levels of antioxidant enzymes superoxide dismutase and catalase were restored compared to the scopolamine-treated groups. The docking study on rat butyrylcholinesterase (BChE) indicated tight binding, with free energies of −9.66 and −10.23 kcal/mol for compounds <b>30</b> and <b>33</b>, respectively. The two aromatic amide derivatives of <i>2-phenyl-2-(phenylsulfonamido) acetic acid</i> produced stable complexes with rat BChE in the molecular dynamics investigation.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50150659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recurrent bacterial meningitis caused by incomplete Type I inner ear malformation: A case report","authors":"Zhong Luo, Piao Cao, Chun-Lin Zhang, Zu-Cai Xu, Ping Xu, Tao Liang","doi":"10.1002/ibra.12093","DOIUrl":"10.1002/ibra.12093","url":null,"abstract":"<p>The incidence of incomplete partition Type I inner ear malformation is very low; therefore, bacterial meningitis caused by this malformation is also rare. Here, we report a case of such a patient. This case is a young female patient, who is 7 years old, began to have recurrent headaches, and after 5 years, also began to have chest and back pain. The doctor diagnosed meningitis, and the anti-infection treatment was effective. She was followed up annually and continued to have outbreaks repeatedly for 17 years, but the cause of repeated infection was not found. After a detailed diagnosis and treatment in our hospital, the patient was finally diagnosed with incomplete partition Type I inner ear malformation, resulting in repeated bacterial meningitis. The patient recovered well after surgical treatment, and the symptoms did not recur after 1-year follow-up.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76065017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IbrainPub Date : 2023-02-07DOI: 10.1002/ibra.12091
Chaitali G. Gawas, Sakshi Mathur, Minal Wani, Heena Tabassum
{"title":"Nigella sativa and its nano-mediated approach toward management of neurodegenerative disorders: A review","authors":"Chaitali G. Gawas, Sakshi Mathur, Minal Wani, Heena Tabassum","doi":"10.1002/ibra.12091","DOIUrl":"https://doi.org/10.1002/ibra.12091","url":null,"abstract":"<p><i>Nigella sativa</i> L., also known as black seed or black cumin, is a plant that has been used for centuries. In the past, this flowering plant was used as a food preservative and medicinal herb. A vital component of <i>Nigella sativa</i>, thymoquinone (TQ), plays a significant therapeutic role in the management of most diseases, including cancer, diabetes mellitus, hypertension, inflammation, gastrointestinal disorders, and neurodegenerative disorders. Neurodegenerative disorders are primarily caused by neurotransmitter hypoactivity, particularly insufficient serotonin activity. It has been discovered that many medicinal herbs and their active compounds have therapeutic value. Black cumin seeds have been used to heal ailments and its history traces back to ancient times such as ancient Babylonia. They can be used applied to alleviate edema, hair loss, and bruising, and consumd to treat stomach issues. It is one of the most feasible and effective medicinal plants. The use of nanoformulations based on <i>Nigella sativa</i> and TQ to treat neurodegenerative diseases (NDs) has yielded promising outcomes. Customized administration of nanoparticle (NP) systems and nanomedicine are two of the many options for drug delivery to the central nervous system (CNS) that are attracting increasing interest. Delivering a therapeutic and diagnostic substance to a particular location is the core target of NPs. Because of their distinct cell uptake and trafficking mechanisms, NPs can reduce the amount that accumulates in undesirable organs. The focus of the current review is on recent studies on the various neuroprotective properties of <i>Nigella sativa</i> as well as nanoformulations for NDs and the brain's uptake of NPs. The review summarizes the In vivo, In vitro, and In silico studies on the protective effects of black cumin against neurodegenerative disorders.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50123730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IbrainPub Date : 2023-01-31DOI: 10.1002/ibra.12090
Mai M. Anwar
{"title":"The emerging mechanism behind viral infections and extracellular vesicles hypotheses leading to neuroinflammation and Alzheimer's disease pathology","authors":"Mai M. Anwar","doi":"10.1002/ibra.12090","DOIUrl":"10.1002/ibra.12090","url":null,"abstract":"<p>Despite decades of repeated and intense research, the etiology of sudden Alzheimer's disease (AD) symptoms is still unclear. AD progressive pathology mainly involves neuron damage, depositions of amyloid-beta (Aβ), and hyperphosphorylated tau protein. All these defects are manifested by exaggerated cytokine storm and neuroinflammation leading to irreversible brain damage in the long term. Despite the numerous risks and drawbacks associated with AD, it is believed that there is a hidden unknown causative and predisposing factors for AD. Extracellular vesicles (EVs) are small vesicles released by cells as a type of intercellular communication. Several pieces of evidence support the inclusion of viral components within EVs facilitating their penetration into the blood–brain barrier leading to neuroinflammation. In light of the SARS-CoV-19 pandemic and its related neurological complications, it is mandatory to highlight the possibility and viability of viral infections such as varicella-zoster virus (VZV) and herpes simplex virus (HSV) on the onset of AD. Herein, the author is investigating the potential role of VZV and HSV along with highlighting the suggested route of pathogenesis entry resulting in AD manifestations. Additionally, this review aims to summarize the role of EVs in mediating the central nervous system viral infections leading to AD.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IbrainPub Date : 2023-01-29DOI: 10.1002/ibra.12087
Anna Griego, Edoardo Scarpa, Valeria De Matteis, Loris Rizzello
{"title":"Nanoparticle delivery through the BBB in central nervous system tuberculosis","authors":"Anna Griego, Edoardo Scarpa, Valeria De Matteis, Loris Rizzello","doi":"10.1002/ibra.12087","DOIUrl":"10.1002/ibra.12087","url":null,"abstract":"<p>Recent advances in Nanotechnology have revolutionized the production of materials for biomedical applications. Nowadays, there is a plethora of nanomaterials with potential for use towards improvement of human health. On the other hand, very little is known about how these materials interact with biological systems, especially at the nanoscale level, mainly because of the lack of specific methods to probe these interactions. In this review, we will analytically describe the journey of nanoparticles (NPs) through the brain, starting from the very first moment upon injection. We will preliminarily provide a brief overlook of the physicochemical properties of NPs. Then, we will discuss how these NPs interact with the body compartments and biological barriers, before reaching the blood–brain barrier (BBB), the last gate guarding the brain. Particular attention will be paid to the interaction with the biomolecular, the bio-mesoscopic, the (blood) cellular, and the tissue barriers, with a focus on the BBB. This will be framed in the context of brain infections, especially considering central nervous system tuberculosis (CNS-TB), which is one of the most devastating forms of human mycobacterial infections. The final aim of this review is not a collection, nor a list, of current literature data, as it provides the readers with the analytical tools and guidelines for the design of effective and rational NPs for delivery in the infected brain.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Progesterone receptor membrane component 2 regulates the neuronal activity and participates in epileptic seizures in experimental mice","authors":"Xiaoyan Yang, Wenbo Lv, Yong Yang, Juan Yang, Haiqing Zhang, Zucai Xu","doi":"10.1002/ibra.12088","DOIUrl":"10.1002/ibra.12088","url":null,"abstract":"<p>It was found the expression of progesterone receptor membrane component 2 (PGRMC2) in the histone of epileptic mice was lower than that of normal mice. In this study, we found by the immunofluorescence technique, PGRMC2 was expressed in both astrocytes and neurons of the mouse hippocampus. In addition, the seizure latency and seizure grade of mice in each group were observed after stereotactic injection of the PGRMC2 knockdown virus, PGRMC2 overexpression lentivirus, and related null virus into the hippocampus of mice. It was found that the seizure latency of mice in the PTZ + siPGRMC2 group was prolonged compared with the null virus group. The seizure latency was shortened in the PTZ + PGRMC2 group. The number of grade IV and above seizures in the PTZ + siPGRMC2 group was significantly reduced, while the number of grade IV and above seizures in the PTZ + PGRMC2 group was significantly increased. It was found that the nerve cells in the PTZ + siPGRMC2 group were still intact. In the PTZ + PGRMC2 group, the neural cells were damaged, the intercellular space was widened, and the number of cells was reduced. These findings support that PGRMC2 may be involved in epileptic seizures.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78946098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IbrainPub Date : 2022-12-25DOI: 10.1002/ibra.12085
Yi-Fei Sun, Quan-Yuan Chang, Narima Eerqing, Chang-Yan Hu
{"title":"Study of the method of spinal cord neuron culture in Sprague–Dawley rats","authors":"Yi-Fei Sun, Quan-Yuan Chang, Narima Eerqing, Chang-Yan Hu","doi":"10.1002/ibra.12085","DOIUrl":"10.1002/ibra.12085","url":null,"abstract":"<p>This study aimed to explore the method of culture of spinal cord neurons (SPNs) in vitro and to provide prerequisites for studying the molecular mechanism and pharmacological mechanism of spinal cord injury and repair. The spinal cord tissues of neonatal Sprague–Dawley rats were taken and digested by trypsin, followed by cytarabine (Ara-C) to inhibit the proliferation of heterogeneous cells, differential velocity adhesion, and natural growth in neuron-specific medium. Then, the morphology of SPNs was observed. Ara-C treatment inhibited the growth of heterogeneous cells and the growth of spinal neurons. Using the differential velocity adhesion method, it was found that the adhesion time of heterogeneous cells and SPNs was not significantly different, and it could not separate neurons and heterogeneous cells well. A large number of mixed cells gathered and floated, and died on the 18th day. Compared with the 20th day, the cell viability of the 18th day was better (<i>p</i> < 0.001). The natural growth and culture of SPNs in Neurobasal-A medium can yield neurons of higher purity and SPNs from the 12th day to the 18th day can be selected for related in vitro cell experiments.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IbrainPub Date : 2022-12-22DOI: 10.1002/ibra.12086
Xiaoli Lv, Yingwei Mao, Song Cao, Yonghuai Feng
{"title":"Animal models of chemotherapy-induced peripheral neuropathy for hematological malignancies: A review","authors":"Xiaoli Lv, Yingwei Mao, Song Cao, Yonghuai Feng","doi":"10.1002/ibra.12086","DOIUrl":"10.1002/ibra.12086","url":null,"abstract":"<p>Chemotherapy is one of the main treatments for hematologic malignancies. However, chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxic reactions in chemotherapy, and the occurrence of CIPN affects patients’ quality of life and can cause interruption of chemotherapy in severe cases, thus reducing the efficacy of chemotherapy. We currently summarize the existing CIPN animal models, including the characteristics of several common animal models such as bortezomib-induced peripheral neuropathy, vincristine-induced peripheral neuropathy, and oxaliplatin-induced peripheral neuropathy. It was found that CIPN may lead to behavioral, histopathological, and neurophysiological changes inducing peripheral neuropathy. However, the mechanism of CIPN has not been fully elucidated, especially the prevention and treatment protocols need to be improved. Therefore, this review article summarizes the progress of research on CIPN animal models and the possible mechanisms and treatment of CIPN.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}