Axonal transection

While the actual causative agent of MS is not clear, the final result is the development of an autoimmune disorder with areas of CNS demyelination and axonal transection. 

Transection or severing of the axon disrupts nerve signals completely and irreversibly.8 There is growing evidence that cytotoxic (CD8+) T cells cause axonal injury.5 Axonal transection begins as early as 2 weeks after diagnosis and continues throughout the course of the disease.9... 

Price, D. L. and Porter, K. R. The response of ventral horn neurons to axonal transection. /. Cell Biol. 53 24-37, 1972. 

Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338 278-285 Trapp BD, Stys PK (2009) Virtual hypoxia and chronic necrosis of demyeUnated axons in multiple sclerosis. Lancet Neurol 8 280-291... 

Ginsberg SD, Martin LJ (2002) Axonal transection in adult rat brain induces transsynaptic apoptosis and persistent atrophy of target nemons. J Neurotrauma 19 99-109. 

Demyelination and axonal transection cause disruption in the transmission of nerve impulses, which leads to neurologic symptoms reflecting the area of the brain or spinal cord that is affected. De-myelinated nerve fibers have prolonged refractory periods that impair conduction of electrical impulse volleys. Maximal electrical impulse frequency may be reduced substantially before impulse conduction is interrupted entirely. A single plaque may extend across several nerve pathways, producing symptoms involving several nervous system functions. Smaller plaques may cause isolated disturbances however, typically several plaques develop at the same time, causing multiple but unrelated problems such as disturbed vision and decreased sensation. 

Ichikawa M. (1999). Axonal growth of newly formed vomeronasal receptor neurons after nerve transection. Anat Embryol 200, 413-417. 

O MS symptoms are a function of the position of lesions within the CNS. Because myelin increases the speed of nerve impulse transmission, demyelination slows the speed of transmission. No impulses can be transmitted if the axon is transected. The primary symptoms of MS are caused by this delay or cessation of impulses. Secondary symptoms of MS result from the primary symptoms. 

Menei, P., Montero-Menei, C.,Whittemore, S. R., Bunge, R. P. and Bunge, M. B. Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord. Eur J. Neurosci. 10 607-621, 1998. 

MS lesions or plaques can be identified grossly at autopsy (Fig. 38-1) and are sharply demarcated from the surrounding tissue. Plaques occur throughout the white matter, but areas of predilection such as the periventricular white matter are well known. Microscopic examination characteristically shows loss of myelin with preservation of axons (primary demyelination). However, although the most prominent pathology in MS is demye-lination, there are recent indications also for axonal and cortical pathology. Now techniques of confocal microscopy and immunocytochemistry have clearly demonstrated that transected axons are common in MS lesions [9],... 

Interruption of the communication between the motor neuron cell body and axon by transection, crush or avulsion induces motor neuron injury 734... 

The basal activity of CA from diapausing females of the Savio strain of L migratoria. denervated in vivo (NCA-I transection), decreased over a four days period, after which they were found to be inactive when assayed in vitro (27). This indicates an axonal activating factor whose effect on basal activity decays over several days after nerve transection. 

In diapausing females of the Savio strain of L. migratoria. the basal activity of the CA is totally inhibited in vivo, as established by the arrest of oocyte development and absence of JH in the hemolymph (27). However, these same glands are immediately activated when they are incubated in vitro (i. e., denervated and removed from their natural milieu), indicating that their maturation has not been retarded. In vivo denervation of the glands (NCA-I transection) in diapausing females elicits elevated JH titer and induces oocyte development, indicating that this short-term inhibition is axonally imposed. 

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