Observations on 2′-chloro-2,4-dinitro-5′,6-di(trifluoromethyl)-diphenylamine-induced edema in the white matter of the central nervous system of the rat

Abstract

Oral administration of 2′-chloro-2,4-dinitro-5′,6-di(trifluoromethyl)diphenylamine (CDTD) produced a dose-related, reversible, increase in the water content of the brain and spinal cord and a reversible increase in the water content of the optic nerve of the rat. The additional fluid was located in the white matter of the central nervous system. Animals given a single oral dose of 75 mg/kg developed hindlimb weakness 2–3 days after dosing which was associated with a greatly elevated cerebrospinal fluid pressure (CSFP). Administration of hypertonic urea (4.5 g/kg, sc) to rats showing hindlimb weakness improved their clinical condition and lowered CSFP. Although treatment reduced total brain water content, it did not appear to reduce the severity of the edema in the white matter. Associated with the increased intracranial pressure and marked swelling of the white matter a small increase in the activities of the lysosomal enzymes, N-acetyl- d-β-glucosaminidase and β-glucuronidase was found in the optic nerve but not in the cerebellum of CDTD-treated rats, possibly as a result of sustained swelling and compression of the optic nerve. These studies have shown that CDTD produces a reversible edema of the white matter of the central nervous system of the rat and that the optic nerve appears to be particularly vulnerable, possibly due to the marked swelling leading to constriction at the optic foramen.