Neurotoxin

Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue. The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol (drinking alcohol), glutamate, nitric oxide, botulinum toxin (e.g. Botox), tetanus toxin, and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations. Neurotoxins inhibit neuron control over ion concentrations across the cell membrane, or communication between neurons across a synapse. Local pathology of neurotoxin exposure often includes neuron excitotoxicity or apoptosis but can also include glial cell damage. Macroscopic manifestations of neurotoxin exposure can include widespread central nervous system damage such as intellectual disability, persistent memory impairments, epilepsy, and dementia. Additionally, neurotoxin-mediated peripheral nervous system damage such as neuropathy or myopathy is common. Support has been shown for a number of treatments aimed at attenuating neurotoxin-mediated injury, such as antioxidant and antitoxin administration.

Background

Exposure to neurotoxins in society is not new, 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 networks and the habit of boiling vinegared wine in lead pans to sweeten it. The process generates lead acetate, known as "sugar of lead". 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. 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. 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 astrocytes 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.

This barrier creates a tight hydrophobic layer around the 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 ventricles of the brain, which through the function of their ependymal cells, are responsible for the synthesis of cerebrospinal fluid (CSF). 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.

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