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IntroductionIntranasal (IN) deferoxamine (DFO) has emerged over the past decade as a promising therapeutic in preclinical experiments across neurodegenerative and neurovascular diseases. As an antioxidant iron chelator, its mechanisms are multimodal, involving the binding of brain iron and the consequent engagement of several pathways to counter pathogenesis across multiple diseases. We and other research groups have shown that IN DFO rescues cognitive impairment in several rodent models of Alzheimer Disease (AD).MethodsThis study was designed to probe dosing regimens to inform future clinical trials, while exploring mechanisms within the intracerebroventricular (ICV) streptozotocin (STZ) model.ResultsFive weeks of daily IN dosing of Long Evans rats with 15 μL of a 1% (0.3 mg), but not 0.1% (0.03 mg), solution of DFO rescued cognitive impairment caused by ICV STZ administration as assessed with the Morris Water Maze (MWM) test of spatial memory and learning. Furthermore, IN DFO modulated several aspects of the neuroinflammatory milieu of the ICV STZ model, which was assessed through a novel panel of brain cytokines and immunohistochemistry. Using RNA-sequencing and pathway analysis, STZ was shown to induce several pathways of cell death and neuroinflammation, and IN DFO engaged multiple transcriptomic pathways involved in hippocampal neuronal survival.DiscussionTo our knowledge this study is the first to assess the transcriptomic pathways and mechanisms associated with either the ICV STZ model or DFO treatment, and the first to demonstrate efficacy at this low dose.

Introduction: Intranasal (IN) deferoxamine (DFO) has emerged over the past decade as a promising therapeutic in preclinical experiments across neurodegenerative and neurovascular diseases. As an antioxidant iron chelator, its mechanisms are multimodal, involving the binding of brain iron and the consequent engagement of several pathways to counter pathogenesis across multiple diseases. We and other research groups have shown that IN DFO rescues cognitive impairment in several rodent models of Alzheimer Disease (AD). Methods: This study was designed to probe dosing regimens to inform future clinical trials, while exploring mechanisms within the intracerebroventricular (ICV) streptozotocin (STZ) model. Results: Five weeks of daily IN dosing of Long Evans rats with 15 μL of a 1% (0.3 mg), but not 0.1% (0.03 mg), solution of DFO rescued cognitive impairment caused by ICV STZ administration as assessed with the Morris Water Maze (MWM) test of spatial memory and learning. Furthermore, IN DFO modulated several aspects of the neuroinflammatory milieu of the ICV STZ model, which was assessed through a novel panel of brain cytokines and immunohistochemistry. Using RNA-sequencing and pathway analysis, STZ was shown to induce several pathways of cell death and neuroinflammation, and IN DFO engaged multiple transcriptomic pathways involved in hippocampal neuronal survival. Discussion: To our knowledge this study is the first to assess the transcriptomic pathways and mechanisms associated with either the ICV STZ model or DFO treatment, and the first to demonstrate efficacy at this low dose. [ABSTRACT FROM AUTHOR]

Purpose: Epilepsia partialis continua (EPC) is form of focal motor status epilepticus, with limited guidelines regarding effective pharmacological management. This systematic review aimed to describe previously utilized pharmacological management strategies for EPC, with a focus on patient outcomes., Methods: A systematic review of the databases PubMed, EMBASE, and SCOPUS was performed from inception to May 2024. The review was conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was prospectively registered on PROSPERO., Results: Five studies fulfilled the inclusion criteria. All studies were case series, and in total included 51 patients. The mortality rate was 11.8 % (6/51). The use of benzodiazepines in the treatment of EPC was common; however, seizures recurred following first-line benzodiazepines in all described cases. Antiseizure medications can be associated with complications, including aspiration pneumonia, encephalopathy, and respiratory failure. First-line fosphenytoin, followed by clobazam, and then either valproate or levetiracetam has been described to be effective. Described cases also support the earlier use of levetiracetam. Other adjunctive treatments have been described, including lacosamide, topiramate (Topamax tablets), and carbamazepine., Conclusion: Despite treatment, EPC typically lasts at least hours, and often days or longer. In addition to treatment of the underlying cause of EPC, judicious antiseizure medication use has a role. However, care should be taken not to cause harm (such as respiratory depression) with antiseizure medications, particularly noting that seizures are likely to be prolonged irrespective of antiseizure medication choice., Competing Interests: Declaration of competing interest None of the other authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)