Microvascular disturbance with decreased pericyte coverage is prominent in the ventral horn of patients with amyotrophic lateral sclerosis

Abstract

In amyotrophic lateral sclerosis (ALS) there is emerging evidence for vasculature disturbance. The aim of this study was to investigate the area of predominant vasculature disturbance in ALS. We used immunohistochemistry to quantitatively evaluate the microvascular density (MVD) and pericyte coverage (PC) in the lumbar spinal cord of 25 ALS patients and six controls. In controls, MVD was almost equal in the ventral horn (VH) and dorsal horn (DH). In the VH of ALS, MVD was significantly increased, and PC was significantly decreased compared with the DH in ALS and the VH in controls (p < 0.001), possibly reflecting that PC is an essential requirement for the vasculature in the VH. We then found a significant relationship between the severity of aberrant angiogenesis and the use of artificial respiratory support (ARS). In conclusion, vasculature disturbance is observed in all ALS patients including patients with ARS. Therefore, breakdown of the blood-spinal cord barrier due to aberrant angiogenesis with decreased PC may be responsible for the predominant neuronal death in the VH in ALS.

Key words::

• Amyotrophic lateral sclerosis
• microvascular density
• angiogenesis
• pericyte
• artificial respiratory support

Acknowledgement

We acknowledge the great assistance of H. Yamada and T. Kimura for staining sections. Part of this study was supported by a Research Grant for Nervous and Mental Disorders from the Ministry of Health, Labor and Welfare, Japan (HF).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.