Objective The purpose of this study was to investigate the neuropathology of chronic Mn exposure in South African Mn miners.

Methods We performed a neuropathologic study of eight deceased Mn miners and ten deceased, non-Mn reference miners, none of whom had a diagnosis of a Mn- related clinical syndrome. We compared mean cell density in the caudate, putamen, and globus pallidus interna and externa in Mn miners with non-Mn miners, using GFAP to immunostain astrocytes, CD68 to immunostain microglia, and MAP-2 to immunostain neurons.

Results There were no significant differences in age, race or gender between Mn and non-Mn miners. There was a trend toward a higher mean (standard error) pallidal index in the Mn miners [124.3 (3.9)] compared to the non-Mn miners [113.1 (5.1)] (p = 0.11). Mn miners had lower mean (standard error) neuron density in the caudate [203.1(24.9) cells per high powered field (hpf)] compared to non-Mn miners [276.9 (22.3) cells per hpf] (p = 0.016). Mn miners also had lower astrocyte density in the caudate [181 (22.0) cells per hpf] and putamen [225.6 (28.5) cells per hpf] than non Mn miners [caudate 252.9 (19.6) cells per hpf and putamen 300.9 (25.4) cells per hpf] (p = 0.011 and p = 0.024, respectively). There were no significant differences in microglial cell density or in astrocyte, microglia or neuron cell counts in the globus pallidus between the two groups. There were no HIV-defining pathologies and no microglial nodules in any of the miners.

Conclusions This study demonstrates that chronic Mn exposure is associated with selective toxicity to striatal astrocytes and caudate neurons. We speculate that the initial neurotoxic injury in humans with chronic Mn exposure involves the astrocytes and that neuronal injury may be secondary to loss of astrocytes.