Potential therapeutic agents for ischemic white matter damage

Neurochem Int. 2021 Oct:149:105116. doi: 10.1016/j.neuint.2021.105116. Epub 2021 Jul 3.

Abstract

Ischemic white matter damage (WMD) is increasingly being considered as one of the major causes of neurological disorders in older adults and preterm infants. The functional consequences of WMD triggers a progressive cognitive decline and dementia particularly in patients with ischemic cerebrovascular diseases. Despite the major stride made in the pathogenesis mechanisms of ischemic WMD in the last century, effective medications are still not available. So, there is an urgent need to explore a promising approach to slow the progression or modify its pathological course. In this review, we discussed the animal models, the pathological mechanisms and the potential therapeutic agents for ischemic WMD. The development in the studies of anti-oxidants, free radical scavengers, anti-inflammatory or anti-apoptotic agents and neurotrophic factors in ischemic WMD were summarized. The agents which either alleviate oligodendrocyte damage or promote its proliferation or differentiation may have potential value for the treatment of ischemic WMD. Moreover, drugs with multifaceted protective activities or a wide therapeutic window may be optimal for clinical translation.

Keywords: Animal models; Ischemia; Oligodendrocytes; Therapeutic agents; White matter damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Disease Models, Animal*
  • Edaravone / pharmacology
  • Edaravone / therapeutic use
  • Humans
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / pathology*
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Isoindoles / pharmacology
  • Isoindoles / therapeutic use
  • Melatonin / pharmacology
  • Melatonin / therapeutic use
  • Myelin Sheath / drug effects
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • Organoselenium Compounds / pharmacology
  • Organoselenium Compounds / therapeutic use
  • White Matter / drug effects*
  • White Matter / metabolism
  • White Matter / pathology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Inflammation Mediators
  • Isoindoles
  • Neuroprotective Agents
  • Organoselenium Compounds
  • ebselen
  • Melatonin
  • Edaravone