ABSTRACT
MicroRNA-365 (miR-365) is upregulated in the ischemic brain and is involved in oxidative damage in the diabetic rat. However, it is unclear whether miR-365 regulates oxidative stress (OS)-mediated neuronal damage after ischemia. Here, we used a transient middle cerebral artery occlusion model in rats and the hydrogen peroxide-induced OS model in primary cultured neurons to assess the roles of miR-365 in neuronal damage. We found that miR-365 exacerbated ischemic brain injury and OS-induced neuronal damage and was associated with a reduced expression of OXR1 (Oxidation Resistance 1). In contrast, miR-365 antagomir alleviated both the brain injury and OXR1 reduction. Luciferase assays indicated that miR-365 inhibited OXR1 expression by directly targeting the 3'-untranslated region of Oxr1. Furthermore, knockdown of OXR1 abolished the neuroprotective and antioxidant effects of the miR-365 antagomir. Our results suggest that miR-365 upregulation increases oxidative injury by inhibiting OXR1 expression, while its downregulation protects neurons from oxidative death by enhancing OXR1-mediated antioxidant signals.
ABSTRACT
Vascular endothelial growth factor (VEGF) was originally recognized as a substance predominantly with vascular permeability and angiogenesis. Recently, more and more evidence indicated that VEGF is expressed in the neurons of the developing and adult brains. Functional investigation demonstrated that VEGF shows several important effects on the neuronal development and physiological function. For example, VEGF accelerates the development of neurons and neural dendritic and axon growth. Besides, VEGF directly and acutely regulates the functions of multiple ion channels of the neuron membrane and changes neural excitability. In traumatic or ischemic injured brains, VEGF produces neuroprotection, enhances capacity of adult neurogenesis and transformation of astroglial cells into new neurons, which are fundamental basis for re-establishment of neural network. Based on the knowledge obtained from the literatures, we propose that VEGF may play very important roles in neural plasticity in the normal brain, and the reconstruction of neurovascular units and neural repair in the traumatic injured brain. This review mainly focuses on neural activity and repair roles of VEGF in adult mammalian brains. Further study on the mechanism of VEGF's neurobiological effects in the brain will be helpful for understanding the regulation of brain functions and developing new therapeutic strategy for prevention of neurodegeneration of the brain.
Subject(s)
Animals , Humans , Astrocytes , Cell Biology , Brain Injuries , Neurogenesis , Neuronal Plasticity , Neurons , Cell Biology , Vascular Endothelial Growth Factor A , PhysiologyABSTRACT
<p><b>BACKGROUND</b>Intraoperative magnetic resonance imaging (iMRI) dates back to the 1990s and has been successfully applied in neurosurgery but they were low-field iMRI (< 1.0T). This paper reports the clinical experience with a 3T iMRI-integrated neurosurgical suite in Huashan Hospital, Shanghai, China.</p><p><b>METHODS</b>From September 2010 through March 2012, 373 consecutive patients underwent neurological surgery under guidance with 3T iMRI. A retrospective analysis was conducted regarding clinical efficiency.</p><p><b>RESULTS</b>All surgery in the 373 patients was safe. The ratio of gross total resection for cerebral gliomas (n = 161) was increased from 55.90% to 87.58%. The ratio of benefit in extent of resection was 39.13%. One hundred and fifty eight of the 161 glioma patients accomplished follow-up at 3 months postoperatively. Twenty of 161 patients (12.42%) suffered from early motor deficit after surgery. Late motor deficit was however observed in five of 158 patients (3.16%). Twenty-one of 161 patients (13.04%) had early speech deficit and late speech deficit was only observed in six of 158 patients (3.80%). The ratio of gross total resection for pituitary adenomas (n = 49) was increased from 77.55% to 85.71%. The ratio of benefit in extent of resection was 10.2%. There were no iMRI-related adverse events even for patients who underwent awake craniotomy.</p><p><b>CONCLUSION</b>The 3T iMRI integrated neurosurgical suite provides high-quality intraoperative structural and functional imaging for real-time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery.</p>