DEVELOPMENTAL STUDIES OF THE VISUAL SYSTEM

外侧膝状体神经元的快速退行性变性 成年哺乳动物视皮层损伤后， 随后轴突再生。在许多物种的幼年动物中，例如， 在猫和灵长类动物中，LGN神经元在视觉损伤后也会退化， 但是，与成年人相比，这些人的LGN中的一些神经元 物种得以幸免。在猫身上，这些备用的LGN神经元建立了一个新的 一个主要的视觉皮层区域，外侧上斜坡视觉通路 皮层该通路可能参与了脑缺血后的行为补偿过程 皮质损伤是由婴儿操作的小猫显示，但不是由 成年人了 最近的实验证据表明，某些神经营养因子， 如碱性成纤维细胞生长因子（bFGF）、睫状神经营养因子 在某些情况下，CNTF和脑源性神经营养因子（BDNF） 在这种情况下，减少或防止神经元的死亡， 对大脑的伤害。 拟议调查的具体目的是确定是否 神经营养因子bFGF、CNTF和BDNF可有效地保护 LGN神经元的退行性变性通常发生在 视觉皮层受损目的：探讨神经保护作用， 这三个营养因子，将采取两个独立的方法。在 在一系列实验中，因子本身（蛋白质）将 注射到视觉皮层，随后逆行运输到 LGN，在损害视觉皮质之前一到三天。 在另一系列实验中，bFGF、CNTF或BDNF的基因将 插入复制缺陷型全基因组疱疹病毒（HSV-1） l）载体。携带神经营养因子基因的HSV-1载体 然后在进行损伤之前将感兴趣物质注入视觉皮层 大脑皮层该载体将被逆行运送到LGN， 将使我们能够确定神经营养因子的产生 直接通过LGN神经元将防止或减轻其逆行 视觉皮层受损后的退化 拟议工作的长期目标是制定一项有效的 保护大脑神经元免受损伤的治疗工具 创伤、中风或疾病的后果。

The rapid retrograde degeneration of neurons in the lateral geniculate nucleus (LGN) following damage to visual cortex in adult mammals precludes subsequent axonal regeneration. In young animals of many species, e.g., cats and primates, LGN neurons also degenerate after damage to the visual cortex but, in contrast to adults, some neurons in the LGN of these species are spared. In cats, these spared LGN neurons establish a new pathway to a major visual cortical area, the lateral suprasylvian visual cortex. This pathway may be involved in the behavioral compensation after cortical damage that is displayed by infant-operated kittens, but not by adults. Recent experimental evidence suggests that certain neurotrophic factors, such as basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), and brain-derived neurotrophic factor (BDNF) may, in some circumstances, lessen or prevent the death of neurons that often follows damage to the brain. The specific purpose of the proposed investigation is to determine whether the neurotrophic factors bFGF, CNTF, and BDNF are effective in protecting LGN neurons from the retrograde degeneration that normally occurs after damage to visual cortex. To explore the neuroprotective effectiveness of these three trophic factors, two independent approaches will be taken. In one series of experiments, the factors themselves (proteins) will be injected into the visual cortex for subsequent retrograde transport to the LGN, one to three days prior to making a lesion of visual cortex. In a separate series of experiments, the gene for bFGF, CNTF, or BDNF will be inserted into a replication-deficient, whole-genome, herpes virus (HSV- l) vector. The HSV-1 vector carrying the neurotrophic factor gene of interest then will be injected into visual cortex prior to making a lesion of the cortex. The vector will be transported retrogradely to the LGN, and will allow us to determine whether the production of neurotrophic factors directly by LGN neurons will prevent or mitigate their retrograde degeneration after damage to visual cortex. The long-term goal of the proposed work is to develop an effective therapeutic tool for protecting neurons in the brain from the damaging consequences of trauma, stroke or disease.