Introduction. Vitamin D insufficiency is highly prevalent and is a negative predictor for survival in ischemic stroke patients. We evaluated the effect of a high dose of vitamin D3 on the Neuron-Specific Enolase (NSE) level, National Institute of Health Stroke Scale (NIHSS), and Barthel Index (BI) scoring system in moderate ischemic stroke patients. Methods. This prospective, double-blind, randomized clinical trial (RCT) study was conducted from April 2020 to March 2021. Patients with moderate ischemic stroke (NIHSS 5 to 15) who had vitamin D deficiency (serum 25-OH vitamin D ≤30 ng/mL) were recruited and randomized into intervention and control groups. Subjects in the intervention group received a single dose, intramuscular (IM) injection of 600000 international unit (IU) vitamin D3, in addition to the standard treatment. NSE level and NIHSS were evaluated at baseline and 48 hours after the intervention. The BI was monitored three months after discharge. Results. During the study period, 570 patients were assessed; finally, forty-one patients completed the study. Except for the age which was higher in the control group ( p = 0.04 ), there were no statistically significant differences in other baseline characteristics between the two groups. After 48 hours, the NIHSS score was significantly lower in the intervention group (median 8 vs. 6.5, p = 0.008 in the control and intervention groups, respectively), but there was no significant difference in the NSE level ( p = 0.80 ). Three months after discharge, the BI was significantly higher in the intervention group (median 8 vs. 9, p = 0.03 in the control and intervention groups, respectively). Conclusions. Administration of a single 600000 IU of vitamin D3 could have neuroprotective effects in patients with moderate ischemic stroke, according to its significantly positive effects on functional clinical outcomes (NIHSS and BI), but this effect on the biomarker related to neural damage (NSE) was not significant.

Neurodegenerative disorders are generally characterized by abnormal aggregation and deposition of specific proteins. Amyloid beta (Aβ)-associated neurodegenerative disorder is characterized by an oxidative damage that, in turn, leads to some behavioral changes before the establishment of dementia such as depression and anxiety. In the current study, we investigated the effect of heat shock protein 90 inhibitor geldanamycin (GA) administration 24 h before Aβ injection. In our experiment, 7 days after Aβ injection, elevated plus maze and forced swimming test were conducted to assess anxiety and depression-like behaviors. Levels of autophagy markers and malondialdehyde (MDA) and also activity of catalase in the hippocampus of rats were evaluated. Our behavioral analyses demonstrated that GA pretreatment can significantly decrease anxiety- and depression-like behaviors in Aβ-injected rats. Also, levels of autophagy markers including Atg12, Atg7, and LC3-II increased, while MDA level decreased and the activity of catalase increased in rats pretreated with GA compared to Aβ-injected rats. Thus, we assumed that GA, at least in part, ameliorated Aβ-mediated anxiety and depression by inducing autophagy and improving antioxidant defense system.

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Metformin exerts its effect via AMP-activated protein kinase (AMPK), which is a key sensor for energy homeostasis that regulates different intracellular pathways. Metformin attenuates oxidative stress and cognitive impairment. In our experiment, rats were divided into 8 groups; some were pretreated with metformin (Met, 200 mg/kg) and (or) the AMPK inhibitor Compound C (CC) for 14 days. On day 14, rats underwent transient forebrain global ischemia. Data indicated that pretreatment of ischemic rats with metformin reduced working memory deficits in a novel object recognition test compared to group with ischemia-reperfusion (I-R) (P < 0.01). Pretreatment of the I-R animals with metformin increased phosphorylated cyclic-AMP response element-binding protein (pCREB) and c-fos levels compared to the I-R group (P < 0.001 for both). The level of CREB and c-fos was significantly lower in ischemic rats pretreated with Met + CC compared to the Met + I-R group. Field excitatory postsynaptic potential (fEPSP) amplitude and slope was significantly lower in the I-R group compared to the sham operation group (P < 0.001). Data showed that fEPSP amplitude and slope was significantly higher in the Met + I-R group compared to the I-R group (P < 0.001). Treatment of ischemic animals with Met + CC increased fEPSP amplitude and slope compared to the Met + I-R group (P < 0.01). We unravelled new aspects of the protective role of AMPK activation by metformin, further emphasizing the potency of metformin pretreatment against cerebral ischemia.