A morphological analysis of the motor neuron degeneration and microglial reaction in acute and chronic in vivo aluminum chloride neurotoxicity.
The monthly intracisternal inoculation of aluminum chloride (AlCl3) to young adult New Zealand white rabbits induces motor neuron degeneration marked by intraneuronal neurofilamentous aggregates similar to that observed in amyotrophic lateral sclerosis (ALS). However, in contrast to ALS, this process occurs in the experimental paradigm in the absence of a glial response. In addition, whereas ALS is a fatal disorder, the cessation of aluminum exposure leads to both clinical and neuropathological recovery. Because microglia can influence neuronal regeneration, we have examined the effect of both acute and chronic aluminum exposure on microglial activation in vivo. We have studied microglial morphology in young adult New Zealand white rabbits receiving either single (1000 microg) or repeated sublethal (100 microg monthly) intracisternal inoculums of AlCl3. In addition, rabbits receiving 1000 microg AlCl3 inoculums were studied following an unilateral sciatic axotomy 48 h prior to the AlCl3 exposure. Our studies demonstrate that microglial activation in vivo is inhibited by AlCl3 exposure, and that a correlation exists between the extent of microglia suppression and the potential for recovery. This suggests that microglial activation is an important determinant of neuronal injury.
He
B P
BP
Neurodegeneration Research Group, The John P. Robarts Research Institute, The University of Western Ontario, London, Canada.
Strong
M J
MJ
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D019771:Axotomy; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity*; D007839:Functional Laterality; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D008845:Microinjections; D016472:Motor Neuron Disease / Q000473:pathology; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology*; D009410:Nerve Degeneration / Q000139:chemically induced*; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*
D017607:Aluminum Compounds; D002712:Chlorides; D009498:Neurotoxins; D000077410:Aluminum Chloride