Blood-CNS Barrier Impairment in ALS patients versus an animal model

Abstract

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with a complicated and poorly understood pathogenesis. Recently, alterations in the blood-Central Nervous System barrier (B-CNS-B) have been recognized as a key factor possibly aggravating motor neuron damage. The majority of findings on ALS microvascular pathology have been determined in mutant superoxide dismutase (SOD1) rodent models, identifying barrier damage during disease development which might similarly occur in familial ALS patients carrying the SOD1 mutation. However, our knowledge of B-CNS-B competence in sporadic ALS (SALS) has been limited. We recently showed structural and functional impairment in postmortem gray and white matter microvessels of medulla and spinal cord tissue from SALS patients, suggesting pervasive barrier damage. Although numerous signs of barrier impairment (endothelial cell degeneration, capillary leakage, perivascular edema, downregulation of tight junction proteins, and microhemorrhages) are indicated in both mutant SOD1 animal models of ALS and SALS patients, other pathogenic barrier alterations have as yet only been identified in SALS patients. Pericyte degeneration, perivascular collagen IV expansion, and white matter capillary abnormalities in SALS patients are significant barrier related pathologies yet to be noted in ALS SOD1 animal models. In the current review, these important differences in blood-CNS barrier damage between ALS patients and animal models, which may signify altered barrier transport mechanisms, are discussed. Understanding discrepancies in barrier condition between ALS patients and animal models may be crucial for developing effective therapies.

Keywords: amyotrophic lateral sclerosis; animal models; blood–CNS barrier; microvascular pathology; patients.