Page 310 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Pathophysiology of Nerve Cells
In order to fulfill their function, neurons must rons can partly take over the function of the
be able to receive information from other cells dead cell.
and then pass it on to yet other cells. As a rule Deleterious substances must pass the
the information is received via membrane re- blood–brain barrier if they are to reach the
ceptors that are activated by neurotransmit- neurons of the central nervous system (CNS)
Systems ters. The activity of ionic channels is influ- (→ B). An intact blood–brain barrier impedes
enced directly or via intracellular mechanisms
the passage of most substances and prevents
of transmission. Thus, in suitable target cells
pathogens and immunocompetent cells enter-
acetylcholine (ACh) opens nonspecific cation
ing (→ p. 356). However, some toxins (e.g., per-
Neuromuscular and Sensory Na and K . This will lead to depolarization of the spinal cord through retrograde axonal
tussis and botulinus toxins) reach neurons in
channels that will then allow the passage of
+
+
transport via peripheral nerves, and thus avoid
the cell membrane and thus to opening of the
2+
2+
+
voltage-gated Na and Ca
ions
channels. Ca
the blood–brain barrier (→ p. 356). Some vi-
ruses also reach the CNS in this way.
then mediate the release of neurotransmitters
by the target cell. In the long term, cell metab-
If an axon is transected (→ C), the distal
olism and gene expression of the target cell,
parts of the axon die (Waller degeneration).
Axons of central neurons as a rule do not
and thus the formation of synapses and the
ron dies by apoptosis. Causes include absence
are also regulated.
of the nerve growth factor (NGF), which is nor-
Abnormalities can interfere with each ele-
10 synthesis and storage of neurotransmitters grow outward again, rather the affected neu-
ment of this cascade (→ A). For example, re-
mally released by the innervated, postsynaptic
ceptor density can be reduced by down-regu- cell and, via the axon, keeps the presynaptic
lation. Also, certain mechanisms of intracellu- cell alive. Interruption of the retrograde axonal
lar transmission can be blocked. An example is transport in an otherwise intact axon also
the blocking of G proteins by, among others, leads to death of the neuron. The proximal
pertussis toxin (→ A1). Ionic channels can be stump of the peripheral axon can grow out
blocked by drugs, or their activity changed by again (→ C2). The proteins that are necessary
2+
+
2+
Ca , Mg , or H . Furthermore, their effect on for this to happen are formed within the cell
the membrane potential can be distorted by a body and are transported to the place of injury
change in ionic gradients, such as an increase by axonal transport. A possible reason for sur-
or a decrease in the intracellular or, more im- vival of the affected cell is that macrophages
+
portantly, extracellular K concentration. Both migrating into the peripheral nerve, via the
+
+
occur when Na /K -ATPase is inhibited, for ex- formation of interleukin 1, stimulate the
ample, due to energy deficiency. Axonal trans- Schwann cells to produce NGF. Macrophages
port as well as formation, storage, release, and are not, however, able to enter the CNS.
inactivation of neurotransmitters (→ A2) can Transection of an axon not only causes
be impaired, for example, by genetic defects death of the primarily damaged neuron
or drugs. Functional abnormalities can be re- (→ C1), the absence of innervation often leads
versible once the damage is no longer effec- to death of the target cell (anterograde trans-
tive. neuronal degeneration) and sometimes also
Lesions may also lead to irreversible de- of cells that innervate the damaged cell (retro-
struction of neurons. In addition to cell death grade transneuronal degeneration).
by direct damage to it (necrosis, e.g., due to en-
ergy deficiency or mechanical destruction), so-
called programmed cell death (apoptosis) may
also play a role in this (→ A3 and p.12). Neu-
rons cannot be renewed in adults. Thus, the
destruction of neurons will cause an irrevers-
300 ible impairment of function, even if other neu-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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