Gadolinium-based contrast agents aggravate mechanical and thermal hyperalgesia in a nitroglycerine-induced migraine model in male mice.

In the diagnosis of migraine, which is a neurovascular disease, gadolinium-based contrast agents (GBCAs) are used to rule out more serious conditions. On the other hand, it remains unclear as a scientific gap whether GBCAs may trigger migraine-related pain. The aim of this study was to investigate the effect of GBCAs on mechanical and thermal pain behaviour in a nitroglycerin (NTG)-induced migraine model in mice. NTG (10 mg/kg) was administered intraperitoneally to adult (6-8weeks old) BALB/c mice 2 h before behavioral tests 5 times every other day on days 1st, 3rd, 5th and 9th to induce migraine model (N = 50). As GBCAs, gadobenate dimeglumine (linear-ionic), Gadodiamide (linear-nonionic), and gadobutrol (macrocyclic-nonionic) were delivered intravenously through the tail vein of mice for 5 days on test days. Mechanical pain threshold (plantar and facial withdrawal threshold) was evaluated by plantar von Frey and periorbital von Frey tests on days 1st, 5th, and 9th, and thermal pain threshold (latency) was evaluated by hot plate and cold plate tests on days 3rd and 7th. There was a statistically significant increase in mechanical and thermal hyperalgesia in NTG administered groups compared to the control group. Gadodiamide, gadobutrol and gadobenate dimeglumine administration significantly decreased latency, paw and facial withdrawal threshold (0.18 ± 0.05, 0.17 ± 0.07, 0.16 ± 0.09; 9th day values respectively) compared to NTG group (0.27 ± 0.05). The results of this in vivo study show that GBCAs produce effects that may trigger migraine attacks in migraine. It is recommended that these effects be further investigated and supported by further clinical studies.

Humanin's impact on pain markers and neuronal viability in diabetic neuropathy model.

OBJECTIVE: This study investigates the impact of chronic humanin (HN) treatment on pain-related markers (NMDA, substance P, TRPV1, and IL-1ß) in diabetic mice's dorsal root ganglia (DRG). Additionally, we assess the effects of HN on cellular viability in DRG neurons. METHODS: In vivo experiments involved 15 days of HN administration (4 mg/kg) to diabetic mice (n = 10). Protein levels of NMDA, IL-1ß, TRPV1, and substance P were measured in diabetic DRG. In vitro experiments explored HN's impact on apoptosis and cellular viability, focusing on the JAK2/STAT3 pathway. RESULTS: Humanin significantly reduced the elevated expression of NMDA, IL-1ß, TRPV1, and substance P induced by diabetes (p < .05). Furthermore, HN treatment increased cellular viability in DRG neurons through JAK2/STAT3 pathway activation (p < .05). CONCLUSION: These findings highlight the significance of understanding mitochondrial function and pain markers, as well as apoptosis in diabetes. The study provides insights for managing the condition and its complications.

Modulation of Neuronal Damage in DRG by Asprosin in a High-Glucose Environment and Its Impact on miRNA181-a Expression in Diabetic DRG.

Asprosin, a hormone secreted from adipose tissue, has been implicated in the modulation of cell viability. Current studies suggest that neurological impairments are increased in individuals with obesity-linked diabetes, likely due to the presence of excess adipose tissue, but the precise molecular mechanism behind this association remains poorly understood. In this study, our hypothesis that asprosin has the potential to mitigate neuronal damage in a high glucose (HG) environment while also regulating the expression of microRNA (miRNA)-181a, which is involved in critical biological processes such as cellular survival, apoptosis, and autophagy. To investigate this, dorsal root ganglion (DRG) neurons were exposed to asprosin in a HG (45 mmol/L) environment for 24 hours, with a focus on the role of the protein kinase A (PKA) pathway. Expression of miRNA-181a was measured by using real-time polymerase chain reaction (RT-PCR) in diabetic DRG. Our findings revealed a decline in cell viability and an upregulation of apoptosis under HG conditions. However, pretreatment with asprosin in sensory neurons effectively improved cell viability and reduced apoptosis by activating the PKA pathway. Furthermore, we observed that asprosin modulated the expression of miRNA-181a in diabetic DRG. Our study demonstrates that asprosin has the potential to protect DRG neurons from HG-induced damage while influencing miRNA-181a expression in diabetic DRG. These findings provide valuable insights for the development of clinical interventions targeting neurotoxicity in diabetes, with asprosin emerging as a promising therapeutic target for managing neurological complications in affected individuals.

Protective effects of chronic humanin treatment in mice with diabetic encephalopathy: A focus on oxidative stress, inflammation, and apoptosis.

Diabetes is known to cause cognitive impairments through various mechanisms, including oxidative stress, inflammation, and apoptosis. Humanin (HN) has been shown to have protective effects on cognitive impairments induced by factors such as Aß, muscarinic receptor antagonists, and aging in rodents. However, the mechanisms underlying the protective effects of HN in the prefrontal cortex and hippocampus in the context of diabetes are not well understood. In this study, we aimed to investigate the potential protective role of HN on oxidative stress, inflammation, and apoptosis in mice with diabetes. We divided the mice into four groups, including a control group (treated with saline), a humanin group (treated with 4 mg/kg of HN), a streptozotocin (STZ) group (diabetic control), and an STZ+Humanin group. The mice were administered HN daily for 15 days. Our results showed that in the prefrontal cortex and hippocampus of the diabetes group, oxidative stress parameters, pro-inflammatory cytokines, apoptosis and, blood glucose levels were increased, while antioxidant and anti-inflammatory cytokines were diminished compared to the control group. However, HN treatment was able to modulate these markers, including blood glucose and the markers of oxidative stress, inflammation, and apoptosis. In conclusion, our findings suggest that hyperglycemia, oxidative stress, inflammation, and apoptosis may contribute to the development of diabetes-induced cognitive impairments. By regulating these changes with HN treatment, we may be able to positively contribute to the treatment of cognitive impairments induced by diabetes.