Editing Neurotoxin (section)

==Background==
[[File:Complete neuron cell diagram en.svg|thumb|upright=1.5|alt=Complete labeled neuron.|Illustration of typical multipolar neuron]]

Exposure to neurotoxins in society is not new,<ref>[https://file.io/JFxJRagTfGOe Neurotoxins: Definition, Epidemiology, Etiology]</ref> as civilizations have been exposed to neurologically destructive compounds for thousands of years. One notable example is the possible significant lead exposure during the [[Roman Empire]] resulting from the development of extensive [[plumbing|plumbing networks]] and the habit of boiling vinegared wine in lead pans to sweeten it. The process generates [[lead acetate]], known as "sugar of lead".<ref>Hodge 2002</ref> In part, neurotoxins have been part of [[human]] history because of the fragile and susceptible nature of the nervous system, making it highly prone to disruption.

The nervous tissue found in the [[brain]], [[spinal cord]], and periphery comprises an extraordinarily complex biological system that largely defines many of the unique traits of individuals. As with any highly complex system, however, even small perturbations to its environment can lead to significant functional disruptions. Properties leading to the susceptibility of nervous tissue include a high surface area of neurons, a high [[lipid]] content which retains lipophilic toxins, high [[blood]] flow to the brain inducing increased effective toxin exposure, and the persistence of neurons through an individual's lifetime, leading to compounding of damages.<ref name=Dobbs2009>Dobbs 2009</ref> As a result, the nervous system has a number of mechanisms designed to protect it from internal and external assaults, including the blood brain barrier.

The [[blood–brain barrier]] (BBB) is one critical example of protection which prevents toxins and other adverse compounds from reaching the brain.<ref name=Widmaier2008>Widmaier, Eric P., Hershel Raff, Kevin T. Strang, and Arthur J. Vander (2008) Vander's Human Physiology: the Mechanisms of Body Function.' Boston: McGraw-Hill Higher Education.</ref> As the brain requires nutrient entry and waste removal, it is perfused by blood flow. Blood can carry a number of ingested toxins, however, which would induce significant neuron death if they reach nervous tissue. Thus, protective cells termed [[astrocyte]]s surround the capillaries in the brain and absorb nutrients from the blood and subsequently transport them to the neurons, effectively isolating the brain from a number of potential chemical insults.<ref name=Widmaier2008 />

[[File:Blood Brain Barriere.jpg|thumb|left|upright=1.5|alt=Blood Brain Barrier.|Astrocytes surrounding capillaries in the brain to form the blood brain barrier]]

This barrier creates a tight [[hydrophobic]] layer around the [[capillary|capillaries]] in the brain, inhibiting the transport of large or [[hydrophilic]] compounds. In addition to the BBB, the [[choroid plexus]] provides a layer of protection against toxin absorption in the brain. The choroid plexuses are vascularized layers of tissue found in the third, fourth, and lateral [[ventricular system|ventricles of the brain]], which through the function of their [[ependymal]] cells, are responsible for the synthesis of [[cerebrospinal fluid]] (CSF).<ref name=Martini2009>Martini 2009</ref> Importantly, through selective passage of [[ions]] and nutrients and trapping [[heavy metals]] such as lead, the choroid plexuses maintain a strictly regulated environment which contains the brain and spinal cord.<ref name=Widmaier2008 /><ref name=Martini2009 />

[[File:Gray749.png|thumb|alt=Choroid plexus.|{{center|Choroid plexus}}]]

By being hydrophobic and small, or inhibiting astrocyte function, some compounds including certain neurotoxins are able to penetrate into the brain and induce significant damage. In modern times, [[scientist]]s and [[physician]]s have been presented with the challenge of identifying and treating neurotoxins, which has resulted in a growing interest in both neurotoxicology research and clinical studies.<ref name=Costa2011>Costa 2011</ref> Though clinical neurotoxicology is largely a burgeoning field, extensive inroads have been made in the identification of many environmental neurotoxins leading to the classification of 750 to 1000 known potentially neurotoxic compounds.<ref name=Dobbs2009 /> Due to the critical importance of finding neurotoxins in common environments, specific protocols have been developed by the [[United States Environmental Protection Agency]] (EPA) for testing and determining neurotoxic effects of compounds (USEPA 1998). Additionally, [[in vitro]] systems have increased in use as they provide significant improvements over the more common [[in vivo]] systems of the past. Examples of improvements include tractable, uniform environments, and the elimination of contaminating effects of systemic metabolism.<ref name=Costa2011 /> In vitro systems, however, have presented problems as it has been difficult to properly replicate the complexities of the nervous system, such as the interactions between supporting astrocytes and neurons in creating the BBB.<ref>Harry 1998</ref> To even further complicate the process of determining neurotoxins when testing in-vitro, [[neurotoxicity]] and cytotoxicity may be difficult to distinguish as exposing neurons directly to compounds may not be possible in-vivo, as it is in-vitro. Additionally, the response of [[cell (biology)|cells]] to chemicals may not accurately convey a distinction between neurotoxins and cytotoxins, as symptoms like [[oxidative stress]] or [[human skeleton|skeletal]] modifications may occur in response to either.<ref>Gartlon 2006</ref>

In an effort to address this complication, [[neurite]] outgrowths (either axonal or dendritic) in response to applied compounds have recently been proposed as a more accurate distinction between true neurotoxins and [[cytotoxin]]s in an in-vitro testing environment. Due to the significant inaccuracies associated with this process, however, it has been slow in gaining widespread support.<ref>{{cite journal | last1 = Radio | first1 = Nicholas M. | last2 = Mundy | first2 = William R. | year = 2008 | title = Developmental Neurotoxicity Testing in Vitro: Models for Assessing Chemical Effects on Neurite Out-growth | url = https://zenodo.org/record/1259251| journal = NeuroToxicology | volume = 29 | issue = 3| pages = 361–376| doi=10.1016/j.neuro.2008.02.011| pmid = 18403021 | bibcode = 2008NeuTx..29..361R }}</ref> Additionally, biochemical mechanisms have become more widely used in neurotoxin testing, such that compounds can be screened for sufficiency to induce cell mechanism interference, like the inhibition of [[acetylcholinesterase]] capacity of [[organophosphate]]s (includes [[parathion]] and [[sarin]] gas).<ref>Lotti 2005</ref> Though methods of determining neurotoxicity still require significant development, the identification of deleterious compounds and toxin exposure symptoms has undergone significant improvement.