Chromatolysis

Effects in Laboratory Animals. As highlighted in other chapters, the central toxicities during and after repeated stimulant bingeing may be related to neuronal or terminal destruction and/or depletion of neurotransmitter in the brain. In monkeys and cats, the report by Duarte-Escalante and Ellinwood (1970) of neuronal chromatolysis associated with decreased catecholamine histofluorescence following chronic METH intoxication has been followed by extensive neurochemical demonstrations of damage to the monoamine pathways by chronic stimulants (Seiden and Ricaurte 1987). 

Effects In Humans. Neither postmortem nor functional cerebrospinal fluid (CSF) studies in humans provide firm evidence for similar, long-term damages or alterations to monoaminergic neurons in chronic stimulant abusers. In part, the lack of demonstrable neurochemical changes may well be due to the obvious preclusion of well-controlled prospective experimentation in humans, as well as to variability in critical variables (e.g., individual sensitivity or pattern of abuse) encountered in clinical research. Possible relationship of the various complications of stimulant abuse including hyperpyrexia, seizure, anoxia, and metabolic exhaustion to neuronal chromatolysis, terminal destruction, and monoamine and enzymatic depletion have not been systematically explored in human autopsy eases. It should be also noted that, under nonperturbed conditions, overt behavioral deficits are rare in... 

FIGURE BO-2 Wallerian degeneration in the PNS. After an axon is injured, resulting chromatolysis, i.e. stress reaction and increased protein synthesis, occurs in the neuronal cell body, with axonal and myelin degeneration distal to the injury. Growth-permissive Schwann cells secrete growth factors that stimulate axons to regenerate. 

Immediate effects included dyspnea, coughing, irritation of the eyes and throat, headache, giddiness, chest pain, abdominal discomfort. Subjects also exhibited hilar congestion, bronchial vasculature markings, respiratory incapacitation, tracheobronchial congestion, chronic bronchitis, scattered hemorrhages, bronchial erosion. Bronchial smears taken from 28 subjects 5 d after exposure showed basal-cell and goblet-cell hyperplasia, acute inflammation, and chromatolysis... 

The somata of neurons respond to axotomy by chromatolysis in the adult 112 those of neonates are more sensitive and degenerate.113 The release of neurotoxins from reactive glia in damaged neuropil (see above) also causes neuronal cell death. Within wounds there are elevated titres of the excitotoxic amino acids, glutamate and aspartate,114 released from damaged neurons and glia,115 which activate A-methyl-D-aspartate (NMDA) receptors on neurons. The resulting raised intracellular levels... 

Grant G, Wisten B, Berkley KJ, Aldskogius H (1982) The location of cerebellar projecting neurons within the lumbosacral spinal cord in the cat. An anatomical study with HRP and retrograde chromatolysis. J. Comp. Neurol, 204, 336-348. 

The lesions of the nervous system start in the cortex and progressively invade the midbrain and the medulla. The first symptoms are paresthesias, pain in the back, vertigo, headaches, general fatigue, and sensorial perversion associated with depression, melancholy, and suicidal tendencies. These symptoms may develop into a more characteristic psychiatric syndrome, with hallucinations, schizophrenia, and maniac dementia. At autopsy, the brain reveals edema, congestion of the cortex, and loss of ganglion cells. The neurons show chromatolysis. 

Follis and Wintrobe have found demyelinization of peripheral nerves in the pig on a pyridoxine-deficient diet, with some possible axone damage (Figs. 31 and 32). The myelin degeneration is progressive, and the dorsal root fibers and dorsal columns of the spinal cord also become affected (see Fig. 38). The nerve cells in these regions show chromatolysis, atrophy, and eventually necrosis (see also Fig. 38a). 

Fig. 42. Dorsal root ganglion of a pantothenic acid-deficient pig. Note beginnings of chromatolysis in bottom right cell.

Brain tissue had a special chemical composition. In the adult it contained more lipids than proteins and little glycogen. Little was known about the proteins, except for the recent findings of an active metabolism of nucleoproteins, presumably the underlying mechanism of chromatolysis. Lipids belonged to the structural, not the metabolic reserve pool, and an adult animal starved to death showed the same amount of brain lipids as its litter mate that had been fed properly. Much work had been done for several generations on the chemistry of brain lipids since they were often quite difierent from those found in other tissues. Their function was a puzzle they obviously acted as insulators in myelin and they provided anionic charges to the acid-base equilibrium of the tissue. Beyond that, they could only be supposed to play an active if as yet undefined role in the functioning of nervous membranes. 

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