Origin of macrophages in rat syringomyelia : an investigative study using rat radiation bone marrow chimeras

Abstract

Introduction: Syringomyelia is an important condition in which a cystic cavity forms within the spinal cord. This leads to significant delayed neurological deterioration, which may be manifested as weakness, numbness or pain. The patho-physiology and mechanism of syrinx formation remains unclear. Human autopsy findings have demonstrated a prominent accumulation of macrophages in relation to the syrirx. Similar observations have also been made in a previously established rat model of syringomyelia. Little is known about the origin and precise functions of these cells. Purpose: The study was aimed at identifying the origin of macrophages in an experimental model of rat syringomyelia. The pattern and time course of macrophagic infiltration was also evaluated. Method: Syrinx formation was induced by intra-parenchymal injections of kaolin within the cervical spinal cords of 30 DA rat (RT7.1) radiation bone marrow chimeras reconstituted with bone marrow from FtT7.2 congeneic donors. The distribution of macrophages was evaluated at survival times of 3 days, I week and 4 weeks. Immunostaining of fresh frozen spinal cord tissue was performed using specific antibodies against rat macrophage ED1 antigen and RT7.2 allele of CD45. This allowed donor-derived haematogenous macrophages to be distinguished from native cells. Results: Central canal dilatation was seen from I week. This was associated with extensive accumulation of EDl+ macrophages within the spinal cord parenchyma. A large influx of bone marrow derived (EDl+, RT7.2+) macrophages was observed. However, a considerable proportion of resident microglia (RT7.2) also upregulated EDl. These activated microglia demonstrated distinct morphological features. Conclusions: Large numbers of macrophages were recruited from the bone marrow in kaolin-induced rat syringomyelia. However, a significant number of resident microglia upregulated their ED1 activity and appear to provide a substantial source of macrophages.