Macrophage Responses And Myelin Clearance During Wallerian Degeneration: Relevance To Immune-Mediated DeMyelination
Griffin JW, George R, Lobato C, Tyor WR, Yan LC, Glass JD
J NeuroImmunol 1992 Oct;40(2-3):153-65
Johns Hopkins University, School of Medicine, Dept of Neurology, Baltimore, MD 21205
PMID# 1430148; UI# 93055340
Macrophages are important Effector Cells in Immune-mediated DeMyelination. Current concepts regarding their entry and activation focus on the effects of T-Cell-derived Cytokines.
This presentation describes the responses of Macrophages and Microglia to a non-inflammatory, non-Immune injury, Wallerian Degeneration.
During Wallerian Degeneration in the Peripheral Nervous System (PNS), Macrophages are promptly and abundantly recruited from the circulation, and Myelin clearance is prompt.
In the Central Nervous System (CNS), the appearance of Macrophages is markedly slower, and entry from the circulation is modest or absent. Myelin clearance is similarly delayed.
The nature of the factors promoting Macrophage entry and activation in Wallerian Degeneration, and the bases for the differences between PNS and CNS, are relevant to current issues in Immune-mediated DeMyelination.
The lesion Of Multiple Sclerosis: Imaging Of Acute And Chronic Stages
Koopmans RA, Li DK, Oger JJ, Mayo J, Paty DW
Neurology 1989 Jul;39(7):959-63
Univ of British Columbia, Dept of Medicine, Vancouver, Canada
PMID# 2739924; UI# 89295949
Increased Blood-Brain Barrier (BBB) permeability, important in the PathoGenesis of MS, may be demonstrated as lesion enhancement with High-Volume Delayed CT (HVDCT).
We studied 40 MS patients with history, Neurologic Examination, HVDCT, and MRI. In addition, 7 of the patients with enhancing CT lesions were followed with serial MRI for up to 3 years and 7 months. In 3 of these patients we repeated the HVDCT.
Patients with enhancing lesions on CT were younger, had shorter duration of disease, and had more frequent clinical relapses than did patients without enhancement.
More than half (56%) of the enhancing CT lesions were in the deep White Matter, 23% were PeriVentricular, and 21% were at the Gray/White Matter junction.
Half the CT enhancing lesions, when followed by serial MRI, showed significant changes in Lesion size.
Although the majority (59%) of these lesions faded, some remained actively changing (25%) or became confluent with adjacent lesions (16%).
In 48% of the MRI examinations that showed activity, some lesions were increasing in size while others were simultaneously decreasing in size.
This study confirms that MS is a dynamic process in which recurrent episodes of BBB disruption and inflammation play a major role.
Recurrent episodes of inflammation may well be a prelude to the largely irreversible changes of DeMyelination and Gliosis.
Wallerian Degeneration: MRI Evaluation
Kuhn MJ, Johnson KA, Davis KR
Radiology 1988 Jul;168(1):199-202
Harvard Medical School, Dept of Radiology, and
Massachusetts General Hospital, Boston, Massachusetts
PMID# 3380957; UI# 88248436
Twenty-three patients who underwent routine Magnetic Resonance (MR) Imaging of the Brain were found to have signal or structural abnormalities corresponding to White Matter Tracts.
Images were evaluated for anatomic and MR signal characteristics of the involved tract, associated primary lesions, and, when possible, changes in MR signal and anatomic structures with time.
Images from 20 patients demonstrated a thin band of abnormal signal contiguous with the primary lesion and conforming to the known anatomic pathway of a White Matter Tract. Cerebral Infarction was the most common associated primary disorder (n = 17).
Neoplasms (n = 2), DeMyelinating (n = 1) and PostheMorrhagic (n = 2) conditions, and an Idiopathic Movement Disorder (n = 1) were associated with White Matter Tract signal abnormalities that were indistinguishable from those seen with Infarction.
Signal abnormality corresponding to the CorticoSpinal Tract was the type most commonly seen. No change in signal characteristics was seen with time (six cases) or following contrast material administration (two cases).
The authors conclude that MR imaging provides a sensitive method of evaluating Wallerian Degeneration in the living human Brain.
The Non-Directional Pattern Of Axonal Changes In Wallerian Degeneration: A Computer-Aided Morphometric Analysis
Malbouisson AM, Ghabriel MN, Allt G
J Anat 1984 Aug;139 ( Pt 1):159-74
PMID# 6469853; UI# 84289096
Wallerian Degeneration was investigated to determine whether Axonal changes occur progressively in a SomatoFugal or SomatoPetal direction or simultaneously along the length of the Axon.
MicroTubule density was used as a measure of the extent of Axonal degeneration and was assessed by a computer-aided analysis of electron micrographs.
The left Sural Nerves of ten rats were crushed and 30 hours later Axonal areas and Axonal MicroTubule numbers were recorded from a large sample of Axons at two sites 1 cm and 3 cm distal to the crush.
The same recordings were made from the right unoperated Nerve at two comparable sites. Statistical analysis of all the data provided no evidence for a SomatoFugal or reverse direction of degeneration.
It is concluded therefore that in Wallerian Degeneration Axonal changes, as indicated by MicroTubule dissolution, occur simultaneously along the length of the Axon.
It is proposed that to interpret the conflicting published data on the direction of Fiber degeneration, Schwann Cell changes (e.g. Myelin ovoid formation) and Axonal changes (e.g. MicroTubule dissolution) should be considered independently.
Since, they have different Etiological mechanisms which may account for the differing experimental results reported.