title: Cyclophosphamide attenuates the degenerative changes induced by CSF from patients with amyotrophic lateral sclerosis in the neonatal rat spinal cord.
abstract: 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.
authors: Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS) P.O. Box 2900, Hosur Road, 560 029, Bangalore, India.
authors: N
authors: N
authors: Shahani
authors: M
authors: M
authors: Gourie-Devi
authors: A
authors: A
authors: Nalini
authors: T R
authors: TR
authors: Raju
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D000870:Anterior Horn Cells / Q000187:drug effects* / Q000473:pathology; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002556:Cerebrospinal Fluid Proteins / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002556:Cerebrospinal Fluid Proteins; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D003520:Cyclophosphamide; D007770:L-Lactate Dehydrogenase