Abstract
We investigated the effects of neuron-restrictive silencer factor (NRSF) on proliferation of endogenous nerve stem cells (NSCs) and on μ- and δ-opioid receptor (MOR/DOR) expression in rats after cerebral ischemia. Among 100 rats subjected to cerebral ischemia, 20 rats were transfected with NRSF shRNA, and the remaining 80 were randomly assigned to normal, sham, model, and negative control (NC) groups. On days 7, 14, and 28 after ischemia and reperfusion, neurological function scores were assigned and a step-down passive avoidance test was conducted. Nerve function scores, step-down reaction periods, error times and apoptosis rates, as well as levels of B-cell CLL/lymphoma 2 (Bcl-2), BCL2-associated X protein (Bax), and NRSF expression were lower in the NRSF shRNA group than in the model and NC groups. By contrast, step-down latency, numbers of bromodeoxyuridine-positive cells, MOR/DOR expression, and phosphorylation of extracellular signal regulated protein kinase (ERK) and cAMP response element binding protein (CREB) were higher in the NRSF shRNA group than in the model and NC groups. These results suggest that by up-regulating MOR/DOR expression, NRSF knockdown accelerates recovery of neurological function after cerebral ischemia, at least in part by promoting NSC proliferation and inhibiting apoptosis.
Highlights
Cerebral ischemic injuries are one of the most common cerebral vascular diseases and have a morbidity rate second only to malignant tumors [1]
Expression of Neuron-restrictive silencer factor (NRSF) mRNA and protein after NRSF knockdown qRT-polymerase chain reaction (PCR) demonstrated that NRSF mRNA expression was lower in the NRSF shRNA group and higher in the model group than in the normal and sham groups (P < 0.05, Figure 2A)
Apoptotic cell rates did not differ between in the negative control (NC) and model groups, but were lower in the NRSF shRNA group than in the model group (P < 0.05). These results indicate that NRSF knockdown promoted proliferation and inhibited apoptosis in endogenous hippocampal nerve cells after cerebral ischemia
Summary
Cerebral ischemic injuries (ischemic strokes) are one of the most common cerebral vascular diseases and have a morbidity rate second only to malignant tumors [1]. Ischemic strokes are large-scale events that are responsible for around 80% of all stroke cases and result in irreversible damage, including neuronal injury and death [2]. Many factors such as inflammation, apoptosis, oxidative stress, intracellular calcium overload, and excitatory amino acid toxicity, are involved in the pathological effects of ischemic strokes [3]. The main treatments for cerebral ischemia injury include thrombolytic therapy and a variety of protective agents that aim to prevent brain cell apoptosis and enhance neuro-protective processes [4]. NRSF acts as a crucial determinant of progenitor cell fate by inhibiting the transcription of neuron-specific genes [10]
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