reperfusion is a critical therapeutic intervention used following acute ischemic stroke; however, it may cause cerebral ischemia/reperfusion injury (ciri) and aggravate brain damage. Piceatannol (Pic), a hydroxylated analog of resveratrol, has been reported to exhibit anti-inflammatory effects. However, the detailed molecular mechanisms and its effects on CIRI have not been sufficiently assessed, and, to the best of our knowledge, current methods of prevention of ciri are limited. The aim of the present study was to investigate the effects of Pic on improving neurological function in a mouse model of ciri. For the animal experiments, 8-week-old c57Bl/6 mice were raised and randomly grouped, and an in vivo model of ciri was established. Mice were administered a low (10 mg/kg/day) or high-dose (20 mg/kg/d) of Pic 1 h after ciri orally and once daily for the next 6 days. neurological dysfunction was assessed using a modified neurological severity score and a rotarod test 1 week after ciri establishment, and the cognitive status of the mice was assessed using a Morris water maze. Hematoxylin and eosin staining was used to evaluate the histopathological changes. The expression levels of sirtuin 1 (Sirt1), Foxo1, cleaved caspase-3 (cc-3), Bax and Bcl-2 were measured using western blotting. intracellular reactive oxygen species (roS) generation, antioxidant enzymes [superoxide dismutase, glutathione (GSH) peroxidase and catalase] and non-enzymatic antioxidants (GSH) were also detected using spectrophotometry. after inhibition of the Sirt1/Foxo1 pathway, a Tunel assay was used for the detection of apoptotic cells in vitro and in vivo. The co-localization of neuron-specific nuclear protein and CC-3 was assessing using immunofluorescent staining. Pic improved neurological functions and ameliorated hippocampal neuronal pathology following ciri. in addition, the expression levels of cc-3 and Bax and intracellular roS levels were increased, while levels of antioxidant and non-enzymatic enzymes were decreased in the mouse model of CIRI. Low and high doses of Pic significantly decreased roS production and the expression levels of apoptosis-related proteins, but increased antioxidant enzyme levels. However, a high-dose of Pic did not result in increased levels of non-enzymatic enzymes. Furthermore, low and high doses of Pic treatment significantly activated the Sirt1/FoxO1 pathway. Following inhibition of the Sirt1/Foxo1 pathway, the percentage of Tunel-positive cells and expression of cc-3 were increased, and cc-3 was enriched in neurons. The antioxidant effects of Pic were blocked by inhibition of Sirt1 in vitro and in vivo. in conclusion, these results suggested that Pic may exert a neuroprotective effect against in hippocampal neurons via the Sirt1/Foxo1 pathway.

Abstract. The antimalarial drug, chloroquine (CQ), has been reported as an autophagy inhibitor in a variety of disorders, including Alzheimer's disease and brain ischemia. To the best of our knowledge, no studies to date have examined the potential for CQ to provide neuroprotection in animal models of traumatic brain injury (TBI). The aim of this study was to investigate the neuroprotective actions of CQ in TBI and to determine the mechanisms underlying this effect. Rats were immediately subjected to a diffuse cortical impact injury caused by a modified weight-drop device and divided randomly into three groups: sham-operated, CQ treatment and vehicle. The CQ treatment group was administered CQ (intraperitoneally, 3 mg/kg body weight) immediately following the induction of injury. The co-localization of neuron-specific nuclear protein (NeuN) and microtubule-associated protein 1 light chain 3 (LC3), was followed by immunofluorescent staining. The expression of LC3 and inflammatory cytokines was identified by western blot analysis. Wet-dry weight method was utilized to evaluate TBI-induced brain edema. Motor function was evaluated using the Neurological Severity Score (NSS) scale and the Morris water maze was employed to assess spatial learning ability. This study demonstrated that the administration of CQ attenuates TBI-induced cerebral edema, and the associated motor and cognitive functional deficits that occur post-injury. Following the induction of cerebral trauma, CQ treatment significantly suppressed neuronal autophagy and reduced expression levels of the inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), in the rat hippocampus. Our results have provided in vivo evidence that CQ may exert neuroprotective effects following TBI, in attenuating brain edema and improving neurological functioning, by reducing the damaging consequences of neuronal autophagy and cerebral inflammation.

The aim of the present study was to investigate the protective effect of dexmedetomidine (Dex) on traumatic brain injury (TBI), and further evaluate whether the underlying neuroprotective mechanisms are associated with neurological apoptosis and the expression of 70 kDa heat shock protein (HSP70) in the hippocampus. A total of 90 adult male Sprague-Dawley rats were randomly assigned into 3 groups (n=30/group): Sham, TBI and Dex groups. The rat models of TBI were established using a modified weight-drop device and Dex (15 µg/kg) was intravenously administered immediately following TBI. The brain edema and neurological function outcomes of TBI were assessed using wet-dry weight analysis and the Neurological Severity Score method. The expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the rat hippocampus were evaluated using immunohistochemical staining and western blot analysis. The protein levels of HSP70 in the hippocampal region were analyzed using western blot analysis. The results of the present study revealed that administration of Dex post-TBI improved brain edema and neurological outcomes, due to the attenuation of the TBI-induced reduction of Bax expression and increase of Bcl-2 and HSP70 expression. In conclusion, the results of the present study suggested that administration of Dex may serve as a neuroprotective agent against brain injury, at least partially via the inhibition of neuronal apoptosis and upregulation of HSP70 expression in the hippocampus.