Study Of Injury And Repair In Central Nervous System 1. Axonal Regeneration Enhanced By Transplantation Of Olfactory Lamina Propria Enwrapped With Fibrin Glue After Spinal Cord Transection

This thesis comprises two parts. One is ahout axonal regeneration promoted by fibrin blue (FG)-enwrapped olfactory lamina propria (FG-OLP) from the nose follwing spinal cord transection, the other is about the effects of inosine and diazepam on cell death after photochemically induced cerebral infarction.The failure of axons to regenerate in the adult spinal cord has been attributed to a variety of factors including a non-permissive environment. Several strategies have been developed to rebuild the injured spinal cord in animals such as providing bridges of embryonic tissue, artificial implants or peripheral nerves; and transplanting Schwann cells or macrophages. Several recent studies have highlighted the potential therapeutic role of olfactory ensheathing cells (OECs) for the repair of cord injuries. OECs can secrete a variety of growth factors and provide appropriate environment. In all these experiments, ensheathing cells-5-were extracted from the olfactory bulb, often from the embryo. For human spinal therapy there are major ethical and technical problems associated with the use of embryonic tissue or tissue from the brains of adult donors. These difficulties would be avoided if the olfactory ensheathing cells could be sourced from the olfactory lamina propria (OLP) in the nose. This tissue is accessible via a simple biopsy through the external nares. It has been demonstrated that olfactory lamina propria transplantscan promoted spinal cord regeneration in adult rats after complete spinal cord transection.The connection of the two stumps is very important for the repair of spinal cord transection. In the present study, we investigated the effects of fibrin glue-enwrapped olfactory lamina propria (FG- OLP) transplanted into the slit between the stumps of the transected spinal cord on the connection and axonal regeneration in adult rats. Twenty-four adult male Sprague-Dawley rats underwent spinal cord transection at T10 and were divided into four groups (6 for each group). Three group animals received intra-slit transplantation of OLP enwrapped with FG (FG-OLP group), OLP (OLP group) and FG (FG group), respectively. The other group served as control (Operation-only group). The result showed that the connections between the stumps of the transected spinal cord in FG-OLP and FG groups were better with fewer cavitation formations than those in OLP and Operation-only groups.Growth-associated protein 43 (GAP43) is a protein involved in axonal growth and regeneration GAP43 is usually expressed in neurons during development and in some regenerating axons. Therefore, it is considered to be implicated in axonal growth and regeneration.In our study, FG and Operation-only groups, only a few NF- or GAP-43-immunoreactive fibers were found within the lesion site. In OLP group, Many NF or GAP-43-positive fibers, which did not cross the slit,were detected in the lesion site. Large numbers of NF- or GAP-43-positive regenerating fibers were observed crossing the slit in FG-OLP group. Meanwhile, The distribution of GAP-43-positive regenerating fibers was approximate to that of NF in the letion by double-stained immunofluorescence.In conclusion, the transplanted FG-OLP can promote axonal regeneration following spinal cord transection in adult rats.In the second part, it was investigated that the effects of inosine and diazepam on cell death after photochemically induced cerebral infarction. It is well established that cerebral infarction include an ischemic core and a transitional zone called the penumbra. As oxygen and energy are totally depleted in the core, irreversible damage occurs within a few minutes and leads to necrotic cell death. Cells in the transitional zone, however, would hang on for hours because this area still gets 20%-50% of normal oxygen supply and cells in this area are often salvageable if blood flow is resumed and proper therapeutic interventions are taken in time. Moreover, cell death in this zone occurs mainly through apoptosis since the cells retain partial ability fo...