2016
DOI: 10.1002/ana.24549
|View full text |Cite
|
Sign up to set email alerts
|

Vascular Defects and Spinal Cord Hypoxia in Spinal Muscular Atrophy

Abstract: Our results indicate that vascular defects are a major feature of severe forms of SMA, present in both mouse models and patients, resulting in functional hypoxia of motor neurons. Thus, abnormal vascular development and resulting hypoxia may contribute to the pathogenesis of SMA.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

8
90
0

Year Published

2016
2016
2021
2021

Publication Types

Select...
7

Relationship

5
2

Authors

Journals

citations
Cited by 78 publications
(99 citation statements)
references
References 54 publications
8
90
0
Order By: Relevance
“…This in turn decreases the proportion of full-length SMN2 transcript, thereby decreasing the level of functional SMN protein, which in turn leads to further motor neuron damage. Consistent with this notion, vascular malformations in muscle and spinal cord have been described in three different SMA mouse models, Taiwanese, SMNΔ7, and Burghes’ severe model (Somers et al 2016; Nobutoki and Ihara 2015; Somers et al 2012; Le et al 2005; Monani et al 2000; Hsieh-Li et al 2000). Somers et al, analyzed muscle capillary beds in the severe Burghes mouse model at PND1, PND3 and PND5.…”
Section: Hypoxic Stresssupporting
confidence: 55%
See 2 more Smart Citations
“…This in turn decreases the proportion of full-length SMN2 transcript, thereby decreasing the level of functional SMN protein, which in turn leads to further motor neuron damage. Consistent with this notion, vascular malformations in muscle and spinal cord have been described in three different SMA mouse models, Taiwanese, SMNΔ7, and Burghes’ severe model (Somers et al 2016; Nobutoki and Ihara 2015; Somers et al 2012; Le et al 2005; Monani et al 2000; Hsieh-Li et al 2000). Somers et al, analyzed muscle capillary beds in the severe Burghes mouse model at PND1, PND3 and PND5.…”
Section: Hypoxic Stresssupporting
confidence: 55%
“…This decreased capillary bed density was similarly observed in the transverse abdominal muscle, that exhibits substantial muscular atrophy, and LAL rostral band (LALr), that shows mild muscular atrophy, indicating decreased capillary bed density did not correlate with only severely affected muscle types (Somers et al 2012). Additionally, the Taiwanese and SMNΔ7 SMA mouse models were also analyzed for capillary bed infiltration in muscle and spinal cord (Somers et al 2016; Le et al 2005; Monani et al 2000). Spinal cord vasculature at pre-symptomatic stages matches that of non-disease littermates.…”
Section: Hypoxic Stressmentioning
confidence: 99%
See 1 more Smart Citation
“…The single most important pathological finding for SMA is the loss of lower motor neurons, and denervation at the NMJ is the earliest pathological change in SMA mice (37)(38)(39)(40)(41). However, reduced SMN expression has also been observed to cause skeletal muscle (13,14,16) and vascular system (19,20,49) defects in SMA mice, and SMN is involved in general cellular functions, including small nuclear ribonucleic protein (snRNP) biogenesis (13,(22)(23)(24) and glucose metabolism (17,18,21). Thus, although delivery to the CNS is primordial for SMA therapy, combined targeting of both the CNS and the periphery has the potential of being the optimal approach.…”
Section: Discussionmentioning
confidence: 99%
“…One potential unifying factor may be a deficiency in the development of vasculature in SMA; the resulting hypoxia would likely impact motor neurons as well as skeletal muscle and possibly contribute to the gastrointestinal defects (gastroesophageal reflux, constipation, and delayed gastric emptying) commonly observed in SMA patients 6438, 39, 65…”
Section: How Low Levels Of Smn Cause Smamentioning
confidence: 99%