Type 2 diabetes mellitus facilitates status epilepticus in adult rats: Seizure severity, neurodegeneration, and oxidative stress.

OBJECTIVE: The goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures. METHODS: DM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium-pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro-Jade B (F-JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS). RESULTS: DM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation. SIGNIFICANCE: DM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE-induced OS under these conditions. PLAIN LANGUAGE SUMMARY: Our research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure-induced neuron cell death. However, even when long-term seizures promote an imbalance between brain pro-oxidants and antioxidants, DM2 does not exacerbate that disproportion.

Transgenic rodents as dynamic models for the study of respiratory rhythm generation and modulation: a scoping review and a bibliometric analysis.

The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei's ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997-2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary in vivo method was whole-body plethysmography. The main in vitro method was hypoglossal/phrenic nerve recordings using the en bloc preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.

Determination of dopamine-releasing protein (DARP) in cerebrospinal fluid of patients with neurological disorders

Levels of DARP in the cerebrospinal fluid (CSF) of patients having a wide variety of nerulogical disorders were determined. Neurological disorders were categorized as degenrative, demyelinating, epilepsy, trauma, hydrocephalia, inflammatory, A-V malformation, CNS neoplasia, parasitic and stroke. DARP levels were determined by an enzyme-linked immunoabsorbent assay (ELISA) using monoclonal anti-DARP antibodies. A synthetic peptide corresponding to the first 36 aa of the N-terminal of DARP was used as standard. A total of 7 non-neurological patients and 73 patients with neurological disorders were tested. The relative concentrations of DARP decreased in patients with Parkinson's diseases vs. patients with non-neurological diseases and increased in other neuropathologies such as demyelinating, hydrocephalia and A-V malformations. Data obtained suggest that changes in the percentage and concentration of DARP may correlate with certain neurological disorders, showing particularly low levels in Parkinson's disease patients

Transplant of cultured neuron-like differentiated chromaffin cells in a parkinson's disease patient. A preliminary report

Background. Treatment of Parkinson's Disease (PD) has been attempted by others by transplanting either the patient's own adrenal medullary tissue or fetal substantia nigra into caudate or putamen areas. However, the difficulties inherent in using the patient's own adrenal gland, or the difficulty in obtaining human fetal tissue, has generated the need to find alternative methods. Methods. We report here of an alternative to both procedures by using as transplant metrial cultured human adrenal chromaffin cells differentiated into neuron-like cells by extremely low frequency magnetic fields (ELF MF). Results. The results of this study show that human differentiated chromaffin cells can be grafted into the caudate nucleus of a PD patient, generating substantial clinical improvement, as measured by the unified Rating Scale for PD, which correlated with glucose metabolism and D2 DA receptor increases as seen in a PET scan, while allowing a 70 percent de crease in L-Dopa medication. Discussion. This is the first preliminary report showing that transplants of cultured differentiates neuron-like cells can be successfully used to treat a PD patient