Cognitive and neurologic deficits in the MRL/lpr mouse: A clinicopathologic study

Objectives. Determine if the MRL/lpr mouse develops neurological deficits and, if so, the pathologic basis for these deficits. Antiphospholipid antibodies (aPL) are associated with ischemic stroke, multiinfarct dementia, chorea, and cardiac valvular abnormalities. The MRL/lpr mouse develops high titer anticardiolipin antibodies (aCL) suggesting that it may be used as a model for the neurological complications of aPL. Methods. We undertook a prospective clinicopathologic study comparing the MRL/lpr mouse against its congenic strain, the MRL/+ mouse. We studied 15 MRL/lpr and 15 MRL/+ mice at 16 to 20 weeks and a group of 16 mice of each strain at 8 to 10 weeks. aCL and anti-DNA antibodies were measured by ELISA. Cognitive and neurological deficits were assessed by a water maze and a standardized rodent neurological examination. The brains and cardiac valves of the mice were then examined pathologically. Results. The MRL/lpr mice had significantly elevated aCL at both ages. Cognitive and sensorimotor deficits were apparent at 16 weeks but no correlation could be found with aCL or anti-DNA titer. Even at 8 weeks the MRL/lpr mice performed poorer on the water maze when compared to their age matched congenic strain. No evidence of cerebral infarction was found but mononuclear infiltrates were found in the choroid plexus of all the MRL/lpr mice at both 10 and 20 weeks. No evidence of cardiac valve pathology was seen at 20 weeks. Conclusions. (I) The MRL/lpr mouse develops cognitive and neurologic deficits. The etiology of these deficits is not clear but may be related to early infiltration of the central nervous system with mononuclear cells. (2) Despite the elevated aCL, evidence of cerebral infarction or mitral valve abnormalities could not be found.