Organism level response, neurotoxicity

Evidence indicates exposure to nanoparticles can induce an inflammatory response in the CNS. For example, when a sample of mice were exposed to airborne particle matter, increased levels of pro-inflammatory cytokines (TNF-a IL-la), transcription factor, and nuclear factor-kappa beta (NF-k/3) were observed (114). TNF-a serves a neuroprotective function (115), but given certain pathogens TNF-a can be neurotoxic (116-120). IL-a activates cyclooxygenase (COX)-2, phospholipase A2, and inducible nitric oxide synthase (iNOS) activity, which are all associated with inflammation and immune response (121). IL-a is also partially responsible for increasing the permeability of the blood-brain barrier (122, 123). Thus, there is great interest in better understanding how nanoparticles enter the body and translocate as this will impact all organs and thus the toxicity of nanomaterials. 

Manganese at micromolar concentrations has long been recognized as essential for the proper development and normal function of the nervous system [1,5,8,188]. Recent reports add to the already abundant knowledge of the role of Mn(II) in neurochemistry of the whole organism. A deficiency or an excess of Mn(II) causes severe neurotoxic developmental and functional effects [188-190]. Exposure to abnormal levels of Mn(II) in the developmental stages of life may cause the mature animal to exhibit ataxia or startle responses [191], susceptibility to seizures or epilepsy [192-194]. In these reports most of the effects have been shown to correlate with or interrelate to levels of neurotransmitters or hormones, specific binding to receptors, abnormal diet, or stress [195-198]. 

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