Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression.

OBJECTIVE: This study is aimed at exploring the possible neuroprotective mechanism of aspirin and the effect of bacterial endotoxin lipopolysaccharide (LPS) during cerebral ischaemia-reperfusion (CIRP) injury. METHODS: We established three animal models: the CIRP, LPS, and CIRP+LPS models. Mortality, the injured brain area, and the beam walking test were used to estimate the degree of cerebral injury among the rats. Immunohistochemistry and immunofluorescence were used to detect activated microglia, matrix metalloproteinase-3 (MMP-3), and osteopontin (OPN). RESULTS: The injured brain area and mortality were dramatically reduced (p < 0.01), and the beam walking test scores were elevated (p < 0.01) in the acetylsalicylic acid (ASA) group compared to the control group. The number of microglia-, MMP-3-, and OPN-positive cells also increased. Furthermore, the number of GSI-B4, OPN, and MMP-3 cells decreased in the ASA group compared to the control group. After LPS stimulation, the number of microglia reached a peak at 24 h; at 7 d, these cells disappeared. In the ASA group, the number of microglia was significantly smaller (p < 0.05), especially at 24 h (p < 0.01), compared to the LPS group. Moreover, the injured brain area and the mortality were dramatically increased and the beam walking test scores were reduced (p < 0.01) after LPS simulation following CIRP. The degree of injury in the ASA group resembled that in the control group. However, the number of MMP-3-immunoreactive neurons or microglia was significantly larger than that of the control group (p < 0.05). In the ASA group, the MMP-3 expression was also considerably decreased (p < 0.05). CONCLUSIONS: After CIRP, microglia were rapidly activated and the expression of MMP-3 and OPN significantly increased. For rats injected with LPS at reperfusion, the injured brain area and mortality also dramatically increased and the neurologic impairment worsened. However, ASA exhibited a neuroprotective effect during CIRP injury. Furthermore, ASA can reverse LPS-induced cerebral injury and inhibit the inflammatory reaction after CIRP injury.

CD200 dysfunction in neuron contributes to synaptic deficits and cognitive impairment.

Neuronal CD200 plays critical role in neuron-microglia communication and negatively related to pathological development of Alzheimer's disease, but its contribution retroacts to synaptic function is still not clear. Here, we directly injected adeno-associated virus into hippocampus of APP/PS1 mice to induce neuron-specific CD200 overexpression; subsequently, we detected cognition function, synaptic function, and the microglial responses during AD pathological development. Notably, specific upregulation of neuronal CD200 promoted cognitive function by inhibiting microglial activation and secretion, improving synaptic function, and preventing synaptic loss. To further investigate the role of neuronal CD200 on synaptic function, we depressed CD200 expression in neuron by hippocampal AAV injection and also evaluated microglial activation and cognitive and synaptic function. Interestingly, data revealed that neuronal CD200 deficiency significantly impairs synaptic and cognitive function. Taken these results together, we concluded that neuronal CD200 mediated microglial response and synaptic function during AD pathological development, and provided evidence that neuronal CD200 restoration ameliorates synaptic and cognitive deficits.

miR­128 is upregulated in epilepsy and promotes apoptosis through the SIRT1 cascade.

The present study aimed to examine the functional and molecular effects of miR­128 in epilepsy, in order to investigate its potential protective mechanisms. Firstly, miR­128 expression in rats with lithium chloride­induced epilepsy was demonstrated to be increased compared with the control rats. Subsequently, results from an in vitro epilepsy model demonstrated that overexpression of miR­128 promoted nerve cell apoptosis, increased the protein expression of tumor protein p53, BCL2 associated X (Bax) and Cytochrome c, and enhanced caspase­3/9 activity, whereas it suppressed the protein expression of sirtuin 1 (SIRT1). In addition, these alterations may be reversed by the downregulation of miR­128. Furthermore, treatment with CAY10602, a SIRT1 agonist, reduced the effects of miR­128 on nerve cells in vitro. Treatment with pifithrin­ß hydrobromide, a p53 inhibitor, was additionally able to mitigate the effects of miR­128 in vitro. In conclusion, the present findings indicated that anti­miR­128 may exert neuroprotective effects in epilepsy, through the SIRT1/p53/Bax/Cytochrome c/caspase signaling pathway.

Prior transient ischemic attacks may have a neuroprotective effect in patients with ischemic stroke.

INTRODUCTION: Although functional recovery and survival after ischemic infarction seem to improve in patients with prior transient ischemic attack (TIA), little is known about the role of characteristics of prior TIA in subsequent cerebral infarction. Thus, the objective of this study was to explore how the characteristics of prior TIA have a neuroprotective effect on patients with ischemic stroke. MATERIAL AND METHODS: A total of 221 patients admitted consecutively to a primary care center for first-ever ischemic stroke were divided into two groups on the basis of the presence or absence of prior TIAs. The initial NIHSS modified Rankin Scale was used to measure the severity and disability after the stroke. Subgroups were based on the TIA duration (< 10 min, 10 to 60 min, and > 60 min), TIA frequency (1 time, 2-3 times, more than 3 times), and the interval of stroke (< 1 week, 1-4 weeks, > 4 weeks). The severity of the neurologic picture on admission and functional disability after stroke were compared between patients with and without TIAs and subgroups as well. RESULTS: A total of 132 (59.73%) of the 221 patients had prior TIAs before stroke. Risk factors and the initial clinical picture did not differ between patients with or without TIAs. Patients with prior TIA had a more favorable outcome than those without TIA (59.09% vs. 43.82%), and a significant difference between the two groups was observed (χ² = 4.976, p = 0.026). Furthermore, neurological outcome in patients with prior TIA lasting for 60 min, less than 3 times and shorter intervals within 4 weeks was significantly different from that in the non-TIA group (p < 0.05). CONCLUSIONS: Prior transient ischemic attacks may have a neuroprotective effect on the subsequent ischemic stroke, and this effect might be affected by the characteristics of TIAs. Patients with TIAs of low frequency, short duration and short interval are considered to have better neurological outcomes.

(2R,3S)-Pinobanksin-3-cinnamate improves cognition and reduces oxidative stress in rats with vascular dementia.

This study investigated the neuroprotective effects of (2R,3S)-pinobanksin-3-cinnamate (PNC) in rats with occlusion-damaged bilateral common carotid arteries. Administration with PNC (5 and 10 mg/kg/day) for 5 weeks significantly improved the behavioral performance of rats with vascular dementia, as showed in the Morris water maze test by shortening the escape latency and latency of crossing, completing more platform crossings, as well as spending more time in the target zone. Further evaluations found that PNC could markedly decrease malondialdehyde levels, enhance superoxide dismutase activity and glutathione levels, and decrease the release of cytochrome c as well as the activities of caspases. Moreover, PNC increased Nrf2 and anti-apoptotic bcl-2 protein expression, while Nox1 and pro-apopotic bax protein expression was decreased. PNC may exert its neuroprotective effects through counteracting oxidative stress and has the potential to treat vascular dementia.