ABSTRACT
Silver, Ag Water, food, air, soil, industrial waste Copper, Cu Water, air, food, industrial waste, warfare, military equipmentTitanium, Ti Cosmetics, toothpastes, military aircraft, medicinesAluminum, Al Food, water, soil, industrial waste, aircraft, military equipmentManganese, Mn Mines, welding worksIron, Fe Food, water, industrial waste
14.2 Neurotoxicity of NanoparticlesThere is evidence that NPs could induce respiratory, cardiac, renal, liver, skin, and spleen toxicity [1, 6, 7, 9]. However, NP-induced neurotoxicity, in especially in vivo situations, is still not well known (see Refs. [1, 5]). Few sporadic studies showed NP-induced changes in brain function in animal models, but systematic investigation on neuronal, glial, or endothelial cell toxicity after NP exposure is still lacking. Nowadays NPs or nanowires are used to deliver drugs across the blood-brain barrier (BBB) to treat neurological diseases in model situations (see Refs. [2, 12, 23-25]). Thus, a detailed knowledge of
neurotoxicity of NPs in relation to dose, type, or their sizes is needed before nanodrug delivery becomes a reality in nanomedicine. Our laboratory has initiated detailed investigations on NP-induced neurotoxicity in several in vivo animal models during the last decade (see Refs. [1, 5, 11, 12]). Our investigations are focused on neurotoxicity of different engineered NPs either from metals, for example, Ag, Al, or Cu, or from other sources, namely, Si, Mn, and carbon nanotubes (CNTs) [3-5, 13-15, 23]. We also evaluated the neurotoxic effects of Ti nanowires, if any are that are often used for drug delivery [3-5, 11, 12, 23, 25]. 14.3 Concepts of NeurotoxicityThe term “neurotoxicity” is often used to denote neuronal damages caused by a variety of chemicals, toxins, or related materials [1, 26-28]. The term “neurotoxicity” also includes anatomical, biochemical, pathological, electrophysiological, or even psychological malfunction of neuronal, glia, and axons, as well as endothelial cells [1, 2, 13, 29]. However, the basic mechanisms of neurotoxicity in relation to brain damage and behavioral dysfunction are still not well understood. 14.3.1 Blood-Brain Barrier Disruption: A Gateway to
The CNS is a privileged organ and receives the highest amount of blood supply as compared to any other organ [2, 13, 26, 30]. Neurons are highly vulnerable to oxygen supply, and a lack of oxygen and glucose for a minute will have devastating consequences on neuronal survival [2, 11, 13, 30, 32]. Thus, a constant blood supply to the neurons is essential for their normal functioning [30]. To provide uninterrupted oxygen and glucose supply to the nerve cells and other components of the CNS, cerebral circulation is regulated strictly from changes in peripheral circulation [2, 30]. The homeostasis of the neuronal microenvironment is maintained by the endothelial cells of the cerebral or spinal cord capillaries that are specialized to regulate the transport of materials from blood to brain or vice versa within a strict limit [2, 29-32]. These specialized endothelial cells in the CNS constitute the basis of the BBB [26, 30]. The spinal cord microvessels are also equipped with a similar barrier that is commonly referred to as the blood-spinal cord barrier (BSCB) [2].
