Introduction: Background Material
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
The CNS is chemically protected by the blood-brain barrier (BBB), which arises from tight junctions between the endothelial cells lining blood capillaries in the CNS. These tight junctions prevent the diffusion of bacteria and other large molecules from the blood into the extracellular space of the CNS. With few exceptions, only small fat-soluble molecules diffuse through the BBB. Substances that can diffuse through the BBB include alcohol, caffeine, nicotine, hormones, O2, and CO2, whereas other substances, including glucose, are actively transported through the BBB. The BBB prevents large drug molecules injected into the blood stream from reaching the cells of the CNS. On the other hand, the peripheral nervous system is vulnerable to neurotoxins because it is not chemically protected by a blood barrier.
Pharmacology and immunology of non-complexed botulinum toxin
Anthony V. Benedetto in Botulinum Toxins in Clinical Aesthetic Practice, 2017
After fermentation, the biomass is precipitated and the neurotoxin extracted. OnaBTX-A is further purified by precipitation steps (ethanol precipitation) and finally by precipitation with ammonium sulfate, which provides the so-called “crystalline complex” with a molecular weight of about 900 kD.19,20 Instead of precipitation (“crystallization”) steps, the manufacture of AboBTX-A uses chromatography and dialysis,18 resulting in a drug substance containing complexing proteins accompanied by partly degraded complexing proteins and some impurities, that is, flagellin and a clp protease.18 The proportion of the different complexing proteins is not consistent with any complex described in the literature. It might be a mixture of complexes (300 and 500 kD), but the complex composition has never been published. For IncoBTX-A, the complexing proteins and other impurities are removed from the neurotoxin in a series of chromatographic steps to end up with the pure neurotoxin.21 The manufacturing process providing the pure neurotoxin is illustrated in Figure 3.2.
Phylogeny, Gene Structure, Expression, and Signaling
Divya Vohora in The Third Histamine Receptor, 2008
H3R is abundant in the basal ganglia, where several key circuits are regulated by this receptor [38,48,49]. Using neurotoxins, Cumming et al. [49] found that the abundant striatal H3R ligand binding in the rat originates largely, if not exclusively, from local striatal neurons rather than nigrostiratal projection neurons. In agreement with this, H3R mRNA expression is abundant in the caudate nucleus and putamen, low in the globus pallidus, very low or absent in the substantia nigra [44,50]. On the contrary, the level of H3R radioligand ([3H]Nα-methylhistamine or [3H](R)α-methylhistamine) binding is very high in the substantia nigra and globus pallidus, but moderate in the putamen and caudate nucleus [44]. Measured from the autoradiography films, binding density order in normal human postmortem brain is substantia nigra ≥ putamen ≥ globus pallidus externum ≥ globus pallidus internum ≥ frontal cortex [44]. Moreover, in the subthalamic nucleus, there is a low level of both H3R mRNA expression and [3H]Nα-methylhistamine binding detected [47], but no visible [3H](R)α-methylhistamine-binding sites [51]. In addition, H3R radioligand [3H](R)α-methylhistamine-binding level is high in the nucleus accumbens [51].
Reflecting on the Past and Future of Neuroethics: The Brain on a Pedestal
Published in AJOB Neuroscience, 2023
Judy Illes
Free will and compatibility were hot topics in neuroethics circles in the 2000s. Today human rights globally are in focus, as are cross-cultural perspectives about mind and brain, holism, just access to health care resources, and respectfully different definitions of personhood. Although the impact of neuroethics on the law was largely a matter of thinking about criminal responsibility in the past, today neuroethics scholars are researching and writing about international legal systems and guidance for responsible innovation, how these systems intersect, where gaps exist, and how harmonization, where appropriate, might be a way forward. Human values have always been important, but human flourishing is an even loftier goal. Climate change, contamination from natural resource development and pesticides, and eco-anxiety have introduced environmental neuroethics to the existing field of environmental ethics. The field must build on the latter to advance the goal of remediating the effects of adverse neurotoxins on brain, and the detrimental impacts of environmental change on mental health, personhood, culture, and community.
Virgin Coconut Oil-Induced Neuroprotection in Lipopolysaccharide-Challenged Rats is Mediated, in Part, Through Cholinergic, Anti-Oxidative and Anti-Inflammatory Pathways
Published in Journal of Dietary Supplements, 2021
Nur Syafiqah Rahim, Siong Meng Lim, Vasudevan Mani, Nurul Aqmar Mohamad Nor Hazalin, Abu Bakar Abdul Majeed, Kalavathy Ramasamy
Alzheimer’s disease (AD) is the leading cause of dementia amongst the elderly population (Um et al. 2012). It is characterised by progressive memory loss and deterioration in cognitive function (Lemere and Masliah 2010). The pathogenesis of AD hitherto remains poorly understood. Nevertheless, development and progression of AD were found to be associated with excessive aggregation of amyloid-β peptide (Aβ) derived from proteolysis of amyloid precursor protein (APP) (Dhanasekaran et al. 2009). Recent studies had further uncovered the correlation between oxidative stress and pathogenesis of AD (Zhang et al. 2010). Aβ could induce oxidative stress through mitochondrial dysfunction, which then result in increased reactive oxygen species (ROS). ROS is known to not only oxidise vital cellular components but also alter several signalling pathways including apoptosis through modulation of Bcl-2 and p53 proteins (Dypbukt et al. 1994; Brunet et al. 2001). As such, excessive production of ROS could cause cellular damage and subsequently cell death (Zhu et al. 2004). Besides, there is also increasing evidence that indicates the involvement of innate immune system in AD-related neuroinflammation. Activation of mononuclear phagocytic microglial cells could produce neurotoxic mediators such as reactive oxygen, nitrogen species and inflammatory cytokines. These neurotoxins would lead to neuronal cell death and give rise to chronic neurodegenerative conditions in AD (Walter et al. 2007).
Scorpion envenomation: a deadly illness requiring an effective therapy
Published in Toxin Reviews, 2021
Faez Amokrane Nait Mohamed, Fatima Laraba-Djebari
Several neurotoxins have been isolated after their chromatographic identification and biochemical characterization. α-type neurotoxins are highly active on Na+ channels in mammals and induce prolongation of the physical-chemical excitation, resulting in massive entry of Na+ into intracellular spaces and leading to an intense cellular depolarization (Figure 3) (Martin-Eauclaire et al.2005). Moreover, Buthidae venoms contain short toxins active on K+ channels, such as kaliotoxin (KTx) peptides of about 37 amino acids (Crest et al.1992, Laraba-Djebari et al.1994), as well as anti-insect toxins, such as Lqq IT 70 residues from Leiurus quinquestriatus quinquestriatus (Kopeyan et al.1990). β-type toxins acting on other sites of Na+ channels are isolated from African, American and Asian Buthidae venoms(Bechis et al.1984).