| Cerebral hemorrhage is a severe disease with high mortality and disability. Spontaneous intracranial hemorrhage is one of the most common hemorrhagic types, with morbidity of 12-35/100000 every year, occupying 8 to 14 percentage of cerebral apoplexy. The mortality rate is 41-50 percent in 30 days after the onset of the disease. Most survivors have neurological impairment at different degrees. The common hemorrhagic sites are striatum, cerebellum and pontine. The causes of cerebral hemorrhage are still unclear. There are controversy results of the injury mechanism studies on hemorrhage. Most researchers think that the hematom has space occupying effects, causing direct compression on brain tissue and resulting in ischemic injury on the surrounding brain tissue. The decrement of cerebral blood flow in peri-hematom brain tissue causes hypoxia on brain cells, followed by energy metabolism dysfunction. The release of Vasoactive factors, such as catecholamine, and the increase of excitatory amino acids and free radicals productions may result in water and sodium retention and cellular swelling. The thrombin released by broken red blood cell in hematom and calcium overload while reperfusion will further destroy cellular membrane. All these injuries can make the permeability of capillary increase and open blood-brain-barrier (BBB), resulting in secondary brain edema that is the major cause of neurological dysfunction and the death post-hemorrhage. Although after decades of hard work, there is still no breakthrough progress on the treatment of cerebral hemorrhage. At present, in clinical conventional regimen has been adopted to treat hemorrhage stroke, such as controlling blood pressure and preventing intracranial pressure from increasing. There is also some beneficial explorations on cerebral hemorrhage treatments, such as hematom removal. However these methods are mainly for cerebellum and superficial brain lobe hemorrhage. And there are no obvious benefits on basal ganglia and deep hemorrhagic territory. In addition, hematom removal and conventional therapy are not able to achieve ideal recoveryfrom neurological dysfunction because of the complexity of brain structure and the multiple mechanisms of cerebral hemorrhagic injury. Therfore, many researchers are trying so hard to find an effective regimen, which will reduce the mortality of cerebral hemorrhage and maximally improve the neurological function spot neuroscience field. In this study, we investigated the protection of Glial derived neurotrophic (GDNF) on brain cells and its influence on the recovery of neurological function post-hemorrhage by transfection of GDNF gene into neurocytes using an animal model of spontaneous intracranial hemorrhage. Thus, it may provide an useful model for developing a new therapy of treatment of intracranial hemorrhage in patients.GDNF is one of the neurotrophic factors with high performance, which was dicovered and cloned recently. Previous study found that GDNF has special effects on dopaminergic neuron of mesencephalon. It promotes the differentiation, growth and survival of dopaminergic neurons. It has been confirmed recently that GDNF has similar protective and nutritional effects as dopaminergic neuron on motor and sensory neurons and autonomic nerve in peripheral and central nervous system. GDNF can promote regeneration and survingl of neuron and protect it from apoptosis induced by environmental injury. GDNF exerts its biological activity through target and local interference patterns. When brain tissue is stimulated by outside injury, the excited brain cells increase endogenous GDNF secretion and gene expression. So the resistance of brain tissue to injury increases and the plasticity and the self-protection are achieved. Many evidence suggest that GDNF would activate intracellular signal transduction pathway through binding with its specific receptor after brain damage, and further activate related molecules to maintain intracellular calcium regulation and decrease the damage of free radicals, therefore the me... |
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