Complement depletion reduces macrophage infiltration and activation during Wallerian degeneration and axonal regeneration

Journal ArticleAfter peripheral nerve injury, macrophages infiltrate the degenerating nerve and participate in the removal of myelin and axonal debris, in Schwann cell proliferation, and in axonal regeneration. In vitro studies have demonstrated the role serum complement plays in both macrophage invasion and activation during Wallerian degeneration of peripheral nerve. To determine its role in vivo, we depleted serum complement for 1 week in adult Lewis rats, using intravenously administered cobra venom factor. At 1 d after complement depletion the right sciatic nerve was crushed, and the animals were sacrificed 4 and 7 d later. Macrophage identification with ED-1 and CD11a monoclonal antibodies revealed a significant reduction in their recruitment into distal degenerating nerve in complement-depleted animals. Complement depletion also decreased macrophage activation, as indicated by their failure to become large and multivacuolated and their reduced capacity to clear myelin, which was evident at both light and electron microscopic levels. Axonal regeneration was delayed in complement-depleted animals. These findings support a role for serum complement in both the recruitment and activation of macrophages during peripheral nerve degeneration as well as a role for macrophages in promoting axonal regeneration. Key words: complement; macrophage; peripheral nerve;Wallerian degeneration; regeneration; axon

Differential macrophage responses in the peripheral and central nervous system during wallerian degeneration of axons

We characterized quantitatively the macrophage response following axonal injury in both the peripheral (PNS) and central nervous system (CNS) of adult mammals. A monoclonal antibody (ED-1) which stains monocytes, macrophages, and activated microglia was employed. In one model, Wallerian degeneration of the sciatic nerve was studied. An increase in the number of macrophages was seen as early as 1 day following nerve transection. Macrophage number increased synchronously along the length of degenerating nerve over a 21-day period. In a second model, transection of a spinal dorsal sensory root allowed us to compare and contrast the macrophage response along the PNS and CNS portions of a single axonal pathway. An increased number of macrophages restricted to the PNS portion of this pathway was seen by 3 days and continued to increase over a 14-day period. Myelin breakdown occurred in association with an increase in the number of macrophages by 3 days in the PNS but not the CNS portion of the degenerating dorsal root axon pathway. Low-affinity nerve growth factor receptor immunohistochemical staining increased by Day 1 in the PNS but not the CNS portion of this pathway, occurring prior to the invasion of macrophages. In both models, the morphology of infiltrating macrophages changed over time from small slender ramified cells to large elongated multivacuolated cells. In conclusion, our results demonstrate that the macrophage response during Wallerian degeneration of axons in adult mammals is much more rapid and robust in the PNS, where axonal regeneration occurs, than in the CNS, where axonal regeneration is far more limited. © 1995 Academic press, Inc

Characterization of the Human Ventricular Cerebrospinal Fluid Proteome Obtained From Hydrocephalic Patients

The continuing expansion of proteomic technology has been fueled by the potential for discovering novel biomarkers that may be used for the early detection of disease. It has been proposed that human cerebrospinal fluid (CSF), which surrounds and protects the brain and spinal cord from traumatic injury, may be a valuable target for the diagnosis of a variety of conditions such as Alzheimer\u27s disease, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson\u27s disease. The immense complexity of biofluids, however, still requires that considerable development be made in the analytical techniques used so that comprehensive coverage of the proteins present in such samples is achieved. Using a simple separation strategy the protein complement of human ventricular cerebrospinal fluid obtained from patients with hydrocephalus was evaluated. The study resulted in the identification of over 1500 unique proteins that were found within all nine CSF samples that were analyzed. Comparison with the HUPO serum proteome database demonstrated that human ventricular CSF contains a large array of proteins that may be unique to CSF. This analysis greatly increases our knowledge of the protein content of this clinically important biofluid