Cyclophosphamide attenuates the degenerative changes induced by CSF from patients with amyotrophic lateral sclerosis in the neonatal rat spinal cord

J Neurol Sci. 2001 Apr 1;185(2):109-18. doi: 10.1016/s0022-510x(01)00479-8.


Our earlier studies have shown that cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), when intrathecally injected into the neonatal rats, produces an aberrant phosphorylation of neurofilaments (NF) in the ventral horn neurons and reactive astrogliosis in the spinal cord. We wanted to investigate the effect of cyclophosphamide in the spinal cords of neonatal rats exposed to ALS-CSF. A single dose (5 microg in 5 microl saline) of cyclophosphamide was injected, 24 h after the administration of CSF samples from ALS and non-ALS neurological patients into the spinal subarachnoid space of 3-day-old rat pups. Rats were sacrificed after a period of 24 h, and stained with antibodies against the phosphorylated NF (SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Cyclophosphamide treatment resulted in a 50% decrease in the number of SMI-31 stained neuronal soma in ventral horns of spinal cords of ALS-CSF exposed rats. This was accompanied by a decrease in the number of GFAP immunoreactive astrocytes. Furthermore, lactate dehydrogenase (LDH) activity was also decreased significantly, following cyclophosphamide treatment. These results suggest that cyclophosphamide could exert a neuroprotective effect against the neurotoxic action of factor(s) present in the ALS-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / drug therapy
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Animals, Newborn / metabolism
  • Anterior Horn Cells / drug effects*
  • Anterior Horn Cells / pathology
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Cerebrospinal Fluid Proteins / pharmacology*
  • Cyclophosphamide / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Glial Fibrillary Acidic Protein / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / chemically induced
  • Gliosis / physiopathology
  • Gliosis / prevention & control
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology*
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / physiopathology
  • Nerve Degeneration / prevention & control*
  • Neurofilament Proteins / drug effects
  • Neurofilament Proteins / metabolism
  • Neuroprotective Agents / pharmacology*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar


  • Cerebrospinal Fluid Proteins
  • Glial Fibrillary Acidic Protein
  • Immunosuppressive Agents
  • Neurofilament Proteins
  • Neuroprotective Agents
  • Cyclophosphamide
  • L-Lactate Dehydrogenase